Research

19 pages, 3061 KiB

Open AccessArticle

Inactivated and Immunogenic SARS-CoV-2 for Safe Use in Immunoassays and as an Immunization Control for Non-Clinical Trials

by Mariana Pierre de Barros Gomes, José Henrique Rezende Linhares, Tiago Pereira dos Santos, Renata Carvalho Pereira, Renata Tourinho Santos, Stephanie Almeida da Silva, Marta Cristina de Oliveira Souza, Juliana Fernandes Amorim da Silva, Gisela Freitas Trindade, Viviane Silva Gomes, Débora Ferreira Barreto-Vieira, Milena Mouta Verdan França Carvalho, Ana Paula Dinis Ano Bom, Noemi Rovaris Gardinali, Rodrigo Müller, Nathalia dos Santos Alves, Luma da Cruz Moura, Patrícia Cristina da Costa Neves, Gabriela Santos Esteves, Waleska Dias Schwarcz, Sotiris Missailidis, Ygara da Silva Mendes and Sheila Maria Barbosa de Lima Show full author list Hide full author list

Viruses 2023, 15(7), 1486; https://0-doi-org.brum.beds.ac.uk/10.3390/v15071486 - 30 Jun 2023

Cited by 2 | Viewed by 1490

Abstract

Successful SARS-CoV-2 inactivation allows its safe use in Biosafety Level 2 facilities, and the use of the whole viral particle helps in the development of analytical methods and a more reliable immune response, contributing to the development and improvement of in vitro and [...] Read more.

Successful SARS-CoV-2 inactivation allows its safe use in Biosafety Level 2 facilities, and the use of the whole viral particle helps in the development of analytical methods and a more reliable immune response, contributing to the development and improvement of in vitro and in vivo assays. In order to obtain a functional product, we evaluated several inactivation protocols and observed that 0.03% beta-propiolactone for 24 h was the best condition tested, as it promoted SARS-CoV-2 inactivation above 99.99% and no cytopathic effect was visualized after five serial passages. Moreover, RT-qPCR and transmission electron microscopy revealed that RNA quantification and viral structure integrity were preserved. The antigenicity of inactivated SARS-CoV-2 was confirmed by ELISA using different Spike-neutralizing monoclonal antibodies. K18-hACE2 mice immunized with inactivated SARS-CoV-2, formulated in AddaS0₃^TM, presented high neutralizing antibody titers, no significant weight loss, and longer survival than controls from a lethal challenge, despite RNA detection in the oropharyngeal swab, lung, and brain. This work emphasizes the importance of using different techniques to confirm viral inactivation and avoid potentially disastrous contamination. We believe that an efficiently inactivated product can be used in several applications, including the development and improvement of molecular diagnostic kits, as an antigen for antibody production as well as a control for non-clinical trials. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

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13 pages, 3530 KiB

Open AccessArticle

SARS-CoV-2 Omicron Specific Mutations Affecting Infectivity, Fusogenicity, and Partial TMPRSS2-Independency

by Romano Strobelt, Karin Broennimann, Julia Adler and Yosef Shaul

Viruses 2023, 15(5), 1129; https://0-doi-org.brum.beds.ac.uk/10.3390/v15051129 - 09 May 2023

Cited by 4 | Viewed by 1714

Abstract

The COVID-19 pandemic resulted from the global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since its first appearance in 2019, new SARS-CoV-2 variants of concern (VOCs) have emerged frequently, changing the infection’s dynamic. SARS-CoV-2 infects cells via two distinct entry [...] Read more.

The COVID-19 pandemic resulted from the global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since its first appearance in 2019, new SARS-CoV-2 variants of concern (VOCs) have emerged frequently, changing the infection’s dynamic. SARS-CoV-2 infects cells via two distinct entry routes; receptor-mediated endocytosis or membrane fusion, depending on the absence or presence of transmembrane serine protease 2 (TMPRSS2), respectively. In laboratory conditions, the Omicron SARS-CoV-2 strain inefficiently infects cells predominantly via endocytosis and is phenotypically characterized by decreased syncytia formation compared to the earlier Delta variant. Thus, it is important to characterize Omicron’s unique mutations and their phenotypic manifestations. Here, by utilizing SARS-CoV-2 pseudovirions, we report that the specific Omicron Spike F375 residue decreases infectivity, and its conversion to the Delta S375 sequence significantly increases Omicron infectivity. Further, we identified that residue Y655 decreases Omicron’s TMPRSS2 dependency and entry via membrane fusion. The Y655H, K764N, K856N and K969N Omicron revertant mutations, bearing the Delta variant sequence, increased the cytopathic effect of cell–cell fusion, suggesting these Omicron-specific residues reduced the severity of SARS-CoV-2. This study of the correlation of the mutational profile with the phenotypic outcome should sensitize our alertness towards emerging VOCs. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

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15 pages, 4833 KiB

Open AccessArticle

GRP78 Inhibitor YUM70 Suppresses SARS-CoV-2 Viral Entry, Spike Protein Production and Ameliorates Lung Damage

by Dat P. Ha, Woo-Jin Shin, Juan Carlos Hernandez, Nouri Neamati, Louis Dubeau, Keigo Machida and Amy S. Lee

Viruses 2023, 15(5), 1118; https://0-doi-org.brum.beds.ac.uk/10.3390/v15051118 - 06 May 2023

Cited by 3 | Viewed by 1977

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 pandemic, has given rise to many new variants with increased transmissibility and the ability to evade vaccine protection. The 78-kDa glucose-regulated protein (GRP78) is a major endoplasmic reticulum (ER) [...] Read more.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 pandemic, has given rise to many new variants with increased transmissibility and the ability to evade vaccine protection. The 78-kDa glucose-regulated protein (GRP78) is a major endoplasmic reticulum (ER) chaperone that has been recently implicated as an essential host factor for SARS-CoV-2 entry and infection. In this study, we investigated the efficacy of YUM70, a small molecule inhibitor of GRP78, to block SARS-CoV-2 viral entry and infection in vitro and in vivo. Using human lung epithelial cells and pseudoviral particles carrying spike proteins from different SARS-CoV-2 variants, we found that YUM70 was equally effective at blocking viral entry mediated by original and variant spike proteins. Furthermore, YUM70 reduced SARS-CoV-2 infection without impacting cell viability in vitro and suppressed viral protein production following SARS-CoV-2 infection. Additionally, YUM70 rescued the cell viability of multi-cellular human lung and liver 3D organoids transfected with a SARS-CoV-2 replicon. Importantly, YUM70 treatment ameliorated lung damage in transgenic mice infected with SARS-CoV-2, which correlated with reduced weight loss and longer survival. Thus, GRP78 inhibition may be a promising approach to augment existing therapies to block SARS-CoV-2, its variants, and other viruses that utilize GRP78 for entry and infection. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

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18 pages, 6148 KiB

Open AccessArticle

Discovery of Highly Potent Small Molecule Pan-Coronavirus Fusion Inhibitors

by Francesca Curreli, Kent Chau, Thanh-Thuy Tran, Isabella Nicolau, Shahad Ahmed, Pujita Das, Christopher D. Hillyer, Mary Premenko-Lanier and Asim K. Debnath

Viruses 2023, 15(4), 1001; https://0-doi-org.brum.beds.ac.uk/10.3390/v15041001 - 19 Apr 2023

Cited by 1 | Viewed by 1625

Abstract

The unprecedented pandemic of COVID-19, caused by a novel coronavirus, SARS-CoV-2, and its highly transmissible variants, led to massive human suffering, death, and economic devastation worldwide. Recently, antibody-evasive SARS-CoV-2 subvariants, BQ and XBB, have been reported. Therefore, the continued development of novel drugs [...] Read more.

The unprecedented pandemic of COVID-19, caused by a novel coronavirus, SARS-CoV-2, and its highly transmissible variants, led to massive human suffering, death, and economic devastation worldwide. Recently, antibody-evasive SARS-CoV-2 subvariants, BQ and XBB, have been reported. Therefore, the continued development of novel drugs with pan-coronavirus inhibition is critical to treat and prevent infection of COVID-19 and any new pandemics that may emerge. We report the discovery of several highly potent small-molecule inhibitors. One of which, NBCoV63, showed low nM potency against SARS-CoV-2 (IC₅₀: 55 nM), SARS-CoV-1 (IC₅₀: 59 nM), and MERS-CoV (IC₅₀: 75 nM) in pseudovirus-based assays with excellent selectivity indices (SI > 900), suggesting its pan-coronavirus inhibition. NBCoV63 showed equally effective antiviral potency against SARS-CoV-2 mutant (D614G) and several variants of concerns (VOCs) such as B.1.617.2 (Delta), B.1.1.529/BA.1 and BA.4/BA.5 (Omicron), and K417T/E484K/N501Y (Gamma). NBCoV63 also showed similar efficacy profiles to Remdesivir against authentic SARS-CoV-2 (Hong Kong strain) and two of its variants (Delta and Omicron), SARS-CoV-1, and MERS-CoV by plaque reduction in Calu-3 cells. Additionally, we show that NBCoV63 inhibits virus-mediated cell-to-cell fusion in a dose-dependent manner. Furthermore, the absorption, distribution, metabolism, and excretion (ADME) data of NBCoV63 demonstrated drug-like properties. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

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6 pages, 518 KiB

Open AccessCommunication

Comparison of Kinetics of Antibody Avidity and IgG Subclasses’ Response in Patients with COVID-19 and Healthy Individuals Vaccinated with the BNT162B2 (Comirnaty, Pfizer/BioNTech) mRNA Vaccine

by Waldemar Rastawicki, Rafał Gierczyński and Aleksandra Anna Zasada

Viruses 2023, 15(4), 970; https://0-doi-org.brum.beds.ac.uk/10.3390/v15040970 - 14 Apr 2023

Cited by 1 | Viewed by 3978

Abstract

There are limited reports concerning the levels of antibodies in IgG subclasses and the avidity of IgG, which is the functional strength with which an antibody binds to an antigen in serum samples obtained at different times after infection or vaccination. This study [...] Read more.

There are limited reports concerning the levels of antibodies in IgG subclasses and the avidity of IgG, which is the functional strength with which an antibody binds to an antigen in serum samples obtained at different times after infection or vaccination. This study investigated the kinetics of antibody avidity and the IgG antibody response within IgG1-IgG4 subclasses in individuals vaccinated with the BNT162B2 mRNA vaccine and in COVID-19 patients. Serum samples were collected from individuals vaccinated with three doses of the BNT162B2 (Comirnaty, Pfizer/BioNTech) vaccine and from unvaccinated COVID-19 patients. This study revealed that IgG1 was a dominating subclass of IgG both in COVID-19 patients and in vaccinated individuals. The level of IgG4 and IgG avidity significantly increased 7 months after the first two doses of the vaccine and then again after the third dose. IgG2 and IgG3 levels were low in most individuals. Investigating IgG avidity and the dynamics of IgG subclasses is essential for understanding the mechanisms of protection against viral infections, including COVID-19, especially in the context of immunization with innovative mRNA vaccines and the possible future development and application of mRNA technology. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

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19 pages, 11848 KiB

Open AccessArticle

Inhibition of Rab1B Impairs Trafficking and Maturation of SARS-CoV-2 Spike Protein

by Christopher Veeck, Nadine Biedenkopf, Cornelius Rohde, Stephan Becker and Sandro Halwe

Viruses 2023, 15(4), 824; https://0-doi-org.brum.beds.ac.uk/10.3390/v15040824 - 24 Mar 2023

Cited by 2 | Viewed by 2144

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) utilizes cellular trafficking pathways to process its structural proteins and move them to the site of assembly. Nevertheless, the exact process of assembly and subcellular trafficking of SARS-CoV-2 proteins remains largely unknown. Here, we have identified and [...] Read more.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) utilizes cellular trafficking pathways to process its structural proteins and move them to the site of assembly. Nevertheless, the exact process of assembly and subcellular trafficking of SARS-CoV-2 proteins remains largely unknown. Here, we have identified and characterized Rab1B as an important host factor for the trafficking and maturation of the spike protein (S) after synthesis at the endoplasmic reticulum (ER). Using confocal microscopy, we showed that S and Rab1B substantially colocalized in compartments of the early secretory pathway. Co-expression of dominant-negative (DN) Rab1B N121I leads to an aberrant distribution of S into perinuclear spots after ectopic expression and in SARS-CoV-2-infected cells caused by either structural rearrangement of the ERGIC or Golgi or missing interaction between Rab1B and S. Western blot analyses revealed a complete loss of the mature, cleaved S2 subunit in cell lysates and culture supernatants upon co-expression of DN Rab1B N121I. In sum, our studies indicate that Rab1B is an important regulator of trafficking and maturation of SARS-CoV-2 S, which not only improves our understanding of the coronavirus replication cycle but also may have implications for the development of antiviral strategies. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

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12 pages, 1260 KiB

Open AccessArticle

Molecular Characterization and Cluster Analysis of SARS-CoV-2 Viral Isolates in Kahramanmaraş City, Turkey: The Delta VOC Wave within One Month

by Nadia Marascio, Merve Cilburunoglu, Elif Gulsum Torun, Federica Centofanti, Elida Mataj, Michele Equestre, Roberto Bruni, Angela Quirino, Giovanni Matera, Anna Rita Ciccaglione and Kezban Tulay Yalcinkaya

Viruses 2023, 15(3), 802; https://0-doi-org.brum.beds.ac.uk/10.3390/v15030802 - 21 Mar 2023

Cited by 1 | Viewed by 1565

Abstract

The SARS-CoV-2 pandemic has seriously affected the population in Turkey. Since the beginning, phylogenetic analysis has been necessary to monitor public health measures against COVID-19 disease. In any case, the analysis of spike (S) and nucleocapsid (N) gene mutations was crucial in determining [...] Read more.

The SARS-CoV-2 pandemic has seriously affected the population in Turkey. Since the beginning, phylogenetic analysis has been necessary to monitor public health measures against COVID-19 disease. In any case, the analysis of spike (S) and nucleocapsid (N) gene mutations was crucial in determining their potential impact on viral spread. We screened S and N regions to detect usual and unusual substitutions, whilst also investigating the clusters among a patient cohort resident in Kahramanmaraş city, in a restricted time span. Sequences were obtained by Sanger methods and genotyped by the PANGO Lineage tool. Amino acid substitutions were annotated comparing newly generated sequences to the NC_045512.2 reference sequence. Clusters were defined using phylogenetic analysis with a 70% cut-off. All sequences were classified as Delta. Eight isolates carried unusual mutations on the S protein, some of them located in the S2 key domain. One isolate displayed the unusual L139S on the N protein, while few isolates carried the T24I and A359S N substitutions able to destabilize the protein. Phylogeny identified nine monophyletic clusters. This study provided additional information about SARS-CoV-2 epidemiology in Turkey, suggesting local transmission of infection in the city by several transmission routes, and highlighting the necessity to improve the power of sequencing worldwide. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

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27 pages, 7781 KiB

Open AccessArticle

Dissecting Phenotype from Genotype with Clinical Isolates of SARS-CoV-2 First Wave Variants

by Mariah K. Taylor, Evan P. Williams, Yi Xue, Piroon Jenjaroenpun, Thidathip Wongsurawat, Amanda P. Smith, Amber M. Smith, Jyothi Parvathareddy, Ying Kong, Peter Vogel, Xueyuan Cao, Walter Reichard, Briana Spruill-Harrell, Amali E. Samarasinghe, Intawat Nookaew, Elizabeth A. Fitzpatrick, Micholas Dean Smith, Michelle Aranha, Jeremy C. Smith and Colleen B. Jonsson

Viruses 2023, 15(3), 611; https://0-doi-org.brum.beds.ac.uk/10.3390/v15030611 - 23 Feb 2023

Cited by 1 | Viewed by 2600

Abstract

The emergence and availability of closely related clinical isolates of SARS-CoV-2 offers a unique opportunity to identify novel nonsynonymous mutations that may impact phenotype. Global sequencing efforts show that SARS-CoV-2 variants have emerged and then been replaced since the beginning of the pandemic, [...] Read more.

The emergence and availability of closely related clinical isolates of SARS-CoV-2 offers a unique opportunity to identify novel nonsynonymous mutations that may impact phenotype. Global sequencing efforts show that SARS-CoV-2 variants have emerged and then been replaced since the beginning of the pandemic, yet we have limited information regarding the breadth of variant-specific host responses. Using primary cell cultures and the K18-hACE2 mouse, we investigated the replication, innate immune response, and pathology of closely related, clinical variants circulating during the first wave of the pandemic. Mathematical modeling of the lung viral replication of four clinical isolates showed a dichotomy between two B.1. isolates with significantly faster and slower infected cell clearance rates, respectively. While isolates induced several common immune host responses to infection, one B.1 isolate was unique in the promotion of eosinophil-associated proteins IL-5 and CCL11. Moreover, its mortality rate was significantly slower. Lung microscopic histopathology suggested further phenotypic divergence among the five isolates showing three distinct sets of phenotypes: (i) consolidation, alveolar hemorrhage, and inflammation, (ii) interstitial inflammation/septal thickening and peribronchiolar/perivascular lymphoid cells, and (iii) consolidation, alveolar involvement, and endothelial hypertrophy/margination. Together these findings show divergence in the phenotypic outcomes of these clinical isolates and reveal the potential importance of nonsynonymous mutations in nsp2 and ORF8. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

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13 pages, 655 KiB

Open AccessArticle

Obesity-Associated Hepatic Steatosis, Somatotropic Axis Impairment, and Ferritin Levels Are Strong Predictors of COVID-19 Severity

by Davide Masi, Elena Gangitano, Anna Criniti, Laura Ballesio, Antonella Anzuini, Luca Marino, Lucio Gnessi, Antonio Angeloni, Orietta Gandini and Carla Lubrano

Viruses 2023, 15(2), 488; https://0-doi-org.brum.beds.ac.uk/10.3390/v15020488 - 09 Feb 2023

Viewed by 1500

Abstract

The full spectrum of SARS-CoV-2-infected patients has not yet been defined. This study aimed to evaluate which parameters derived from CT, inflammatory, and hormonal markers could explain the clinical variability of COVID-19. We performed a retrospective study including SARS-CoV-2–infected patients hospitalized from March [...] Read more.

The full spectrum of SARS-CoV-2-infected patients has not yet been defined. This study aimed to evaluate which parameters derived from CT, inflammatory, and hormonal markers could explain the clinical variability of COVID-19. We performed a retrospective study including SARS-CoV-2–infected patients hospitalized from March 2020 to May 2021 at the Umberto I Polyclinic of Rome. Patients were divided into four groups according to the degree of respiratory failure. Routine laboratory examinations, BMI, liver steatosis indices, liver CT attenuation, ferritin, and IGF-1 serum levels were assessed and correlated with severity. Analysis of variance between groups showed that patients with worse prognoses had higher BMI and ferritin levels, but lower liver density, albumin, GH, and IGF-1. ROC analysis confirmed the prognostic accuracy of IGF-1 in discriminating between patients who experienced death/severe respiratory failure and those who did not (AUC 0.688, CI: 0.587 to 0.789, p < 0.001). A multivariate analysis considering the degrees of severity of the disease as the dependent variable and ferritin, liver density, and the standard deviation score of IGF-1 as regressors showed that all three parameters were significant predictors. Ferritin, IGF-1, and liver steatosis account for the increased risk of poor prognosis in COVID-19 patients with obesity. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

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15 pages, 3044 KiB

Open AccessArticle

Structural and Immunoreactivity Properties of the SARS-CoV-2 Spike Protein upon the Development of an Inactivated Vaccine

by Larisa V. Kordyukova, Andrey V. Moiseenko, Marina V. Serebryakova, Marina A. Shuklina, Maria V. Sergeeva, Dmitry A. Lioznov and Andrei V. Shanko

Viruses 2023, 15(2), 480; https://0-doi-org.brum.beds.ac.uk/10.3390/v15020480 - 09 Feb 2023

Cited by 4 | Viewed by 1996

Abstract

Inactivated vaccines are promising tools for tackling the COVID-19 pandemic. We applied several protocols for SARS-CoV-2 inactivation (by β-propiolactone, formaldehyde, and UV radiation) and examined the morphology of viral spikes, protein composition of the preparations, and their immunoreactivity in ELISA using two panels [...] Read more.

Inactivated vaccines are promising tools for tackling the COVID-19 pandemic. We applied several protocols for SARS-CoV-2 inactivation (by β-propiolactone, formaldehyde, and UV radiation) and examined the morphology of viral spikes, protein composition of the preparations, and their immunoreactivity in ELISA using two panels of sera collected from convalescents and people vaccinated by Sputnik V. Transmission electron microscopy (TEM) allowed us to distinguish wider flail-like spikes (supposedly the S-protein’s pre-fusion conformation) from narrower needle-like ones (the post-fusion state). While the flails were present in all preparations studied, the needles were highly abundant in the β-propiolactone-inactivated samples only. Structural proteins S, N, and M of SARS-CoV-2 were detected via mass spectrometry. Formaldehyde and UV-inactivated samples demonstrated the highest affinity/immunoreactivity against the convalescent sera, while β-propiolactone (1:2000, 36 h) and UV-inactivated ones were more active against the sera of people vaccinated with Sputnik V. A higher concentration of β-propiolactone (1:1000, 2 h) led to a loss of antigenic affinity for both serum panels. Thus, although we did not analyze native SARS-CoV-2 for biosafety reasons, our comparative approach helped to exclude some destructive inactivation conditions and select suitable variants for future animal research. We believe that TEM is a valuable tool for inactivated COVID-19 vaccine quality control during the downstream manufacturing process. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

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8 pages, 485 KiB

Open AccessArticle

A Polymorphism in the TMPRSS2 Gene Increases the Risk of Death in Older Patients Hospitalized with COVID-19

by Clara Caldeira de Andrade, Ana Tércia Paulo Silva, Luydson Richardson Silva Vasconcelos, Pablo Rafael Silveira Oliveira, Carlos Dornels Freire de Souza, Anderson da Costa Armstrong and Rodrigo Feliciano do Carmo

Viruses 2022, 14(11), 2557; https://0-doi-org.brum.beds.ac.uk/10.3390/v14112557 - 18 Nov 2022

Cited by 8 | Viewed by 2029

Abstract

Background: Transmembrane serine protease type 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2) are the main molecules involved in the entry of SARS-CoV-2 into host cells. Changes in TMPRSS2 expression levels caused by single nucleotide polymorphisms (SNPs) may contribute to the outcome of COVID-19. [...] Read more.

Background: Transmembrane serine protease type 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2) are the main molecules involved in the entry of SARS-CoV-2 into host cells. Changes in TMPRSS2 expression levels caused by single nucleotide polymorphisms (SNPs) may contribute to the outcome of COVID-19. The aim was to investigate the association between TMPRSS2 gene polymorphisms and the risk of death in hospitalized patients with COVID-19. Methods: We included patients with confirmed COVID-19, recruited from two hospitals in northeastern Brazil from August 2020 to July 2021. Two functional polymorphisms (rs2070788 and rs12329760) in TMPRSS2 were evaluated by real-time PCR. The Kaplan–Meier method was used to estimate death. The Cox’s proportional hazards model was used to adjust for potentially confounding factors. Results: A total of 402 patients were followed prospectively. Survival analysis demonstrated that older patients carrying the rs2070788 GG genotype had shorter survival times when compared to those with AG or AA genotypes (p = 0.009). In multivariable analysis, the GG genotype was a factor independently associated with the risk of death in older individuals (hazard ratio = 4.03, 95% confidence interval 1.49 to 10.84). Conclusions: The rs2070788 polymorphism in TMPRSS2 increases risk of death four-fold in older patients hospitalized with COVID-19. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

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15 pages, 2973 KiB

Open AccessArticle

Molecular Dynamics Simulations to Decipher the Role of Phosphorylation of SARS-CoV-2 Nonstructural Proteins (nsps) in Viral Replication

by Lamya Alomair, Sabeena Mustafa, Mohsin Saleet Jafri, Wardah Alharbi, Abdulrhman Aljouie, Fahad Almsned, Mohammed Alawad, Yahya Abdulfattah Bokhari and Mamoon Rashid

Viruses 2022, 14(11), 2436; https://0-doi-org.brum.beds.ac.uk/10.3390/v14112436 - 02 Nov 2022

Cited by 4 | Viewed by 2286

Abstract

Protein phosphorylation is a post-translational modification that enables various cellular activities and plays essential roles in protein interactions. Phosphorylation is an important process for the replication of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). To shed more light on the effects of phosphorylation, [...] Read more.

Protein phosphorylation is a post-translational modification that enables various cellular activities and plays essential roles in protein interactions. Phosphorylation is an important process for the replication of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). To shed more light on the effects of phosphorylation, we used an ensemble of neural networks to predict potential kinases that might phosphorylate SARS-CoV-2 nonstructural proteins (nsps) and molecular dynamics (MD) simulations to investigate the effects of phosphorylation on nsps structure, which could be a potential inhibitory target to attenuate viral replication. Eight target candidate sites were found as top-ranked phosphorylation sites of SARS-CoV-2. During the process of molecular dynamics (MD) simulation, the root-mean-square deviation (RMSD) analysis was used to measure conformational changes in each nsps. Root-mean-square fluctuation (RMSF) was employed to measure the fluctuation in each residue of 36 systems considered, allowing us to evaluate the most flexible regions. These analysis shows that there are significant structural deviations in the residues namely nsp1 THR 72, nsp2 THR 73, nsp3 SER 64, nsp4 SER 81, nsp4 SER 455, nsp5 SER284, nsp6 THR 238, and nsp16 SER 132. The identified list of residues suggests how phosphorylation affects SARS-CoV-2 nsps function and stability. This research also suggests that kinase inhibitors could be a possible component for evaluating drug binding studies, which are crucial in therapeutic discovery research. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

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12 pages, 1215 KiB

Open AccessArticle

SARS-CoV-2 Production, Purification Methods and UV Inactivation for Proteomics and Structural Studies

by Zlatka Plavec, Aušra Domanska, Xiaonan Liu, Pia Laine, Lars Paulin, Markku Varjosalo, Petri Auvinen, Sharon G. Wolf, Maria Anastasina and Sarah J. Butcher

Viruses 2022, 14(9), 1989; https://0-doi-org.brum.beds.ac.uk/10.3390/v14091989 - 08 Sep 2022

Cited by 6 | Viewed by 2656

Abstract

Severe acute respiratory syndrome coronavirus-2 is the causative agent of COVID-19. During the pandemic of 2019–2022, at least 500 million have been infected and over 6.3 million people have died from COVID-19. The virus is pleomorphic, and due to its pathogenicity is often [...] Read more.

Severe acute respiratory syndrome coronavirus-2 is the causative agent of COVID-19. During the pandemic of 2019–2022, at least 500 million have been infected and over 6.3 million people have died from COVID-19. The virus is pleomorphic, and due to its pathogenicity is often handled in very restrictive biosafety containments laboratories. We developed two effective and rapid purification methods followed by UV inactivation that allow easy downstream handling of the virus. We monitored the purification through titering, sequencing, mass spectrometry and electron cryogenic microscopy. Although pelleting through a sucrose cushion, followed by gentle resuspension overnight gave the best particle recovery, infectivity decreased, and the purity was significantly worse than if using the size exclusion resin Capto Core. Capto Core can be used in batch mode, and was seven times faster than the pelleting method, obviating the need for ultracentrifugation in the containment laboratory, but resulting in a dilute virus. UV inactivation was readily optimized to allow handling of the inactivated samples under standard operating conditions. When containment laboratory space is limited, we recommend the use of Capto Core for purification and UV for inactivation as a simple, rapid workflow prior, for instance, to electron cryogenic microscopy or cell activation experiments. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

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10 pages, 9422 KiB

Open AccessArticle

Neutralizing Antibody Response to Sarbecovirus Is Delayed in Sequential Heterologous Immunization

by Huibin Lv, Ray T. Y. So, Qi Wen Teo, Meng Yuan, Hejun Liu, Chang-Chun D. Lee, Garrick K. Yip, Wilson W. Ng, Ian A. Wilson, Malik Peiris, Nicholas C. Wu and Chris Ka Pun Mok

Viruses 2022, 14(7), 1382; https://0-doi-org.brum.beds.ac.uk/10.3390/v14071382 - 24 Jun 2022

Cited by 2 | Viewed by 1741

Abstract

Antigenic imprinting, which describes the bias of the antibody response due to previous immune history, can influence vaccine effectiveness. While this phenomenon has been reported for viruses such as influenza, there is little understanding of how prior immune history affects the antibody response [...] Read more.

Antigenic imprinting, which describes the bias of the antibody response due to previous immune history, can influence vaccine effectiveness. While this phenomenon has been reported for viruses such as influenza, there is little understanding of how prior immune history affects the antibody response to SARS-CoV-2. This study provides evidence for antigenic imprinting through immunization with two Sarbecoviruses, the subgenus that includes SARS-CoV-2. Mice were immunized subsequently with two antigenically distinct Sarbecovirus strains, namely SARS-CoV-1 and SARS-CoV-2. We found that sequential heterologous immunization induced cross-reactive binding antibodies for both viruses and delayed the emergence of neutralizing antibody responses against the booster strain. Our results provide fundamental knowledge about the immune response to Sarbecovirus and important insights into the development of pan-sarbecovirus vaccines and guiding therapeutic interventions. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

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21 pages, 3450 KiB

Open AccessArticle

Borneol Ester Derivatives as Entry Inhibitors of a Wide Spectrum of SARS-CoV-2 Viruses

by Olga I. Yarovaya, Dmitriy N. Shcherbakov, Sophia S. Borisevich, Anastasiya S. Sokolova, Maxim A. Gureev, Edward M. Khamitov, Nadezda B. Rudometova, Anastasiya V. Zybkina, Ekaterina D. Mordvinova, Anna V. Zaykovskaya, Artem D. Rogachev, Oleg V. Pyankov, Rinat A. Maksyutov and Nariman F. Salakhutdinov

Viruses 2022, 14(6), 1295; https://0-doi-org.brum.beds.ac.uk/10.3390/v14061295 - 14 Jun 2022

Cited by 15 | Viewed by 2968

Abstract

In the present work we studied the antiviral activity of the home library of monoterpenoid derivatives using the pseudoviral systems of our development, which have glycoproteins of the SARS-CoV-2 virus strains Wuhan and Delta on their surface. We found that borneol derivatives with [...] Read more.

In the present work we studied the antiviral activity of the home library of monoterpenoid derivatives using the pseudoviral systems of our development, which have glycoproteins of the SARS-CoV-2 virus strains Wuhan and Delta on their surface. We found that borneol derivatives with a tertiary nitrogen atom can exhibit activity at the early stages of viral replication. In order to search for potential binding sites of ligands with glycoprotein, we carried out additional biological tests to study the inhibition of the re-receptor-binding domain of protein S. For the compounds that showed activity on the pseudoviral system, a study using three strains of the infectious SARS-CoV-2 virus was carried out. As a result, two leader compounds were found that showed activity on the Wuhan, Delta, and Omicron strains. Based on the biological results, we searched for the potential binding site of the leader compounds using molecular dynamics and molecular docking methods. We suggested that the compounds can bind in conserved regions of the central helices and/or heptad repeats of glycoprotein S of SARS-CoV-2 viruses. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

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12 pages, 17124 KiB

Open AccessArticle

A Novel Method to Reduce ELISA Serial Dilution Assay Workload Applied to SARS-CoV-2 and Seasonal HCoVs

by David Pattinson, Peter Jester, Lizheng Guan, Seiya Yamayoshi, Shiho Chiba, Robert Presler, Hongyu Rao, Kiyoko Iwatsuki-Horimoto, Nobuhiro Ikeda, Masao Hagihara, Tomoyuki Uchida, Keiko Mitamura, Peter Halfmann, Gabriele Neumann and Yoshihiro Kawaoka

Viruses 2022, 14(3), 562; https://0-doi-org.brum.beds.ac.uk/10.3390/v14030562 - 09 Mar 2022

Cited by 3 | Viewed by 2895

Abstract

Assays using ELISA measurements on serially diluted serum samples have been heavily used to measure serum reactivity to SARS-CoV-2 antigens and are widely used in virology and elsewhere in biology. We test a method using Bayesian hierarchical modelling to reduce the workload of [...] Read more.

Assays using ELISA measurements on serially diluted serum samples have been heavily used to measure serum reactivity to SARS-CoV-2 antigens and are widely used in virology and elsewhere in biology. We test a method using Bayesian hierarchical modelling to reduce the workload of these assays and measure reactivity of SARS-CoV-2 and HCoV antigens to human serum samples collected before and during the COVID-19 pandemic. Inflection titers for SARS-CoV-2 full-length spike protein (S1S2), spike protein receptor-binding domain (RBD), and nucleoprotein (N) inferred from 3 spread-out dilutions correlated with those inferred from 8 consecutive dilutions with an R² value of 0.97 or higher. We confirm existing findings showing a small proportion of pre-pandemic human serum samples contain cross-reactive antibodies to SARS-CoV-2 S1S2 and N, and that SARS-CoV-2 infection increases serum reactivity to the beta-HCoVs OC43 and HKU1 S1S2. In serial dilution assays, large savings in resources and/or increases in throughput can be achieved by reducing the number of dilutions measured and using Bayesian hierarchical modelling to infer inflection or endpoint titers. We have released software for conducting these types of analysis. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

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5 pages, 785 KiB

Open AccessCommunication

Comparison of Plaque Size, Thermal Stability, and Replication Rate among SARS-CoV-2 Variants of Concern

by Gi Uk Jeong, Gun Young Yoon, Hyun Woo Moon, Wooseong Lee, Insu Hwang, Haesoo Kim, Kyun-Do Kim, Chonsaeng Kim, Dae-Gyun Ahn, Bum-Tae Kim, Seong-Jun Kim and Young-Chan Kwon

Viruses 2022, 14(1), 55; https://0-doi-org.brum.beds.ac.uk/10.3390/v14010055 - 30 Dec 2021

Cited by 13 | Viewed by 3224

Abstract

SARS-CoV-2, like other RNA viruses, has a propensity for genetic evolution owing to the low fidelity of its viral polymerase. Several recent reports have described a series of novel SARS-CoV-2 variants. Some of these have been identified as variants of concern (VOCs), including [...] Read more.

SARS-CoV-2, like other RNA viruses, has a propensity for genetic evolution owing to the low fidelity of its viral polymerase. Several recent reports have described a series of novel SARS-CoV-2 variants. Some of these have been identified as variants of concern (VOCs), including alpha (B.1.1.7, Clade GRY), beta (B.1.351, Clade GH), gamma (P.1, Clade GR), and delta (B.1.617.2, Clade G). VOCs are likely to have some effect on transmissibility, antibody evasion, and changes in therapeutic or vaccine effectiveness. However, the physiological and virological understanding of these variants remains poor. We demonstrated that these four VOCs exhibited differences in plaque size, thermal stability at physiological temperature, and replication rates. The mean plaque size of beta was the largest, followed by those of gamma, delta, and alpha. Thermal stability, evaluated by measuring infectivity and half-life after prolonged incubation at physiological temperature, was correlated with plaque size in all variants except alpha. However, despite its relatively high thermal stability, alpha’s small plaque size resulted in lower replication rates and fewer progeny viruses. Our findings may inform further virological studies of SARS-CoV-2 variant characteristics, VOCs, and variants of interest. These studies are important for the effective management of the COVID-19 pandemic. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

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18 pages, 22788 KiB

Open AccessArticle

Differential Effect of SARS-CoV-2 Spike Glycoprotein 1 on Human Bronchial and Alveolar Lung Mucosa Models: Implications for Pathogenicity

by Mizanur Rahman, Martin Irmler, Sandeep Keshavan, Micol Introna, Johannes Beckers, Lena Palmberg, Gunnar Johanson, Koustav Ganguly and Swapna Upadhyay

Viruses 2021, 13(12), 2537; https://0-doi-org.brum.beds.ac.uk/10.3390/v13122537 - 17 Dec 2021

Cited by 10 | Viewed by 3953

Abstract

Background: The SARS-CoV-2 spike protein mediates attachment of the virus to the host cell receptor and fusion between the virus and the cell membrane. The S1 subunit of the spike glycoprotein (S1 protein) contains the angiotensin converting enzyme 2 (ACE2) receptor binding domain. [...] Read more.

Background: The SARS-CoV-2 spike protein mediates attachment of the virus to the host cell receptor and fusion between the virus and the cell membrane. The S1 subunit of the spike glycoprotein (S1 protein) contains the angiotensin converting enzyme 2 (ACE2) receptor binding domain. The SARS-CoV-2 variants of concern contain mutations in the S1 subunit. The spike protein is the primary target of neutralizing antibodies generated following infection, and constitutes the viral component of mRNA-based COVID-19 vaccines. Methods: Therefore, in this work we assessed the effect of exposure (24 h) to 10 nM SARS-CoV-2 recombinant S1 protein on physiologically relevant human bronchial (bro) and alveolar (alv) lung mucosa models cultured at air–liquid interface (ALI) (n = 6 per exposure condition). Corresponding sham exposed samples served as a control. The bro-ALI model was developed using primary bronchial epithelial cells and the alv-ALI model using representative type II pneumocytes (NCI-H441). Results: Exposure to S1 protein induced the surface expression of ACE2, toll like receptor (TLR) 2, and TLR4 in both bro-ALI and alv-ALI models. Transcript expression analysis identified 117 (bro-ALI) and 97 (alv-ALI) differentially regulated genes (p ≤ 0.01). Pathway analysis revealed enrichment of canonical pathways such as interferon (IFN) signaling, influenza, coronavirus, and anti-viral response in the bro-ALI. Secreted levels of interleukin (IL) 4 and IL12 were significantly (p < 0.05) increased, whereas IL6 decreased in the bro-ALI. In the case of alv-ALI, enriched terms involving p53, APRIL (a proliferation-inducing ligand) tight junction, integrin kinase, and IL1 signaling were identified. These terms are associated with lung fibrosis. Further, significantly (p < 0.05) increased levels of secreted pro-inflammatory cytokines IFNγ, IL1ꞵ, IL2, IL4, IL6, IL8, IL10, IL13, and tumor necrosis factor alpha were detected in alv-ALI, whereas IL12 was decreased. Altered levels of these cytokines are also associated with lung fibrotic response. Conclusions: In conclusion, we observed a typical anti-viral response in the bronchial model and a pro-fibrotic response in the alveolar model. The bro-ALI and alv-ALI models may serve as an easy and robust platform for assessing the pathogenicity of SARS-CoV-2 variants of concern at different lung regions. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

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Review

Jump to: Research, Other

16 pages, 2127 KiB

Open AccessReview

SARS-CoV-2 ORF8: A Rapidly Evolving Immune and Viral Modulator in COVID-19

by Ariana Arduini, Frederique Laprise and Chen Liang

Viruses 2023, 15(4), 871; https://0-doi-org.brum.beds.ac.uk/10.3390/v15040871 - 29 Mar 2023

Cited by 9 | Viewed by 5373

Abstract

The COVID-19 pandemic has resulted in upwards of 6.8 million deaths over the past three years, and the frequent emergence of variants continues to strain global health. Although vaccines have greatly helped mitigate disease severity, SARS-CoV-2 is likely to remain endemic, making it [...] Read more.

The COVID-19 pandemic has resulted in upwards of 6.8 million deaths over the past three years, and the frequent emergence of variants continues to strain global health. Although vaccines have greatly helped mitigate disease severity, SARS-CoV-2 is likely to remain endemic, making it critical to understand its viral mechanisms contributing to pathogenesis and discover new antiviral therapeutics. To efficiently infect, this virus uses a diverse set of strategies to evade host immunity, accounting for its high pathogenicity and rapid spread throughout the COVID-19 pandemic. Behind some of these critical host evasion strategies is the accessory protein Open Reading Frame 8 (ORF8), which has gained recognition in SARS-CoV-2 pathogenesis due to its hypervariability, secretory property, and unique structure. This review discusses the current knowledge on SARS-CoV-2 ORF8 and proposes actualized functional models describing its pivotal roles in both viral replication and immune evasion. A better understanding of ORF8’s interactions with host and viral factors is expected to reveal essential pathogenic strategies utilized by SARS-CoV-2 and inspire the development of novel therapeutics to improve COVID-19 disease outcomes. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

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17 pages, 1209 KiB

Open AccessReview

Human Coronavirus OC43 as a Low-Risk Model to Study COVID-19

by Mi Il Kim and Choongho Lee

Viruses 2023, 15(2), 578; https://0-doi-org.brum.beds.ac.uk/10.3390/v15020578 - 20 Feb 2023

Cited by 6 | Viewed by 6717

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has had irreversible and devastating impacts on every aspect of human life. To better prepare for the next similar pandemic, a clear understanding of coronavirus biology is a prerequisite. Nevertheless, the high-risk nature of the causative agent [...] Read more.

The coronavirus disease 2019 (COVID-19) pandemic has had irreversible and devastating impacts on every aspect of human life. To better prepare for the next similar pandemic, a clear understanding of coronavirus biology is a prerequisite. Nevertheless, the high-risk nature of the causative agent of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), requires the use of a cumbersome biosafety level-3 (BSL-3) confinement facility. To facilitate the development of preventive and therapeutic measures against SARS-CoV-2, one of the endemic strains of low-risk coronaviruses has gained attention as a useful research alternative: human coronavirus OC43 (HCoV-OC43). In this review, its history, classification, and clinical manifestations are first summarized. The characteristics of its viral genomes, genes, and evolution process are then further explained. In addition, the host factors necessary to support the life cycle of HCoV-OC43 and the innate, as well as adaptive, immunological responses to HCoV-OC43 infection are discussed. Finally, the development of in vitro and in vivo systems to study HCoV-OC43 and its application to the discovery of potential antivirals for COVID-19 by using HCoV-OC43 models are also presented. This review should serve as a concise guide for those who wish to use HCoV-OC43 to study coronaviruses in a low-risk research setting. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

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28 pages, 490 KiB

Open AccessReview

Cell and Animal Models for SARS-CoV-2 Research

by Eloïne Bestion, Philippe Halfon, Soraya Mezouar and Jean-Louis Mège

Viruses 2022, 14(7), 1507; https://0-doi-org.brum.beds.ac.uk/10.3390/v14071507 - 09 Jul 2022

Cited by 10 | Viewed by 2406

Abstract

During the last two years following the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, development of potent antiviral drugs and vaccines has been a global health priority. In this context, the understanding of virus pathophysiology, the identification of associated therapeutic targets, and [...] Read more.

During the last two years following the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, development of potent antiviral drugs and vaccines has been a global health priority. In this context, the understanding of virus pathophysiology, the identification of associated therapeutic targets, and the screening of potential effective compounds have been indispensable advancements. It was therefore of primary importance to develop experimental models that recapitulate the aspects of the human disease in the best way possible. This article reviews the information concerning available SARS-CoV-2 preclinical models during that time, including cell-based approaches and animal models. We discuss their evolution, their advantages, and drawbacks, as well as their relevance to drug effectiveness evaluation. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

14 pages, 1539 KiB

Open AccessReview

SARS-CoV-2: Evolution and Emergence of New Viral Variants

by Verónica Roxana Flores-Vega, Jessica Viridiana Monroy-Molina, Luis Enrique Jiménez-Hernández, Alfredo G. Torres, José Ignacio Santos-Preciado and Roberto Rosales-Reyes

Viruses 2022, 14(4), 653; https://0-doi-org.brum.beds.ac.uk/10.3390/v14040653 - 22 Mar 2022

Cited by 34 | Viewed by 10819

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent responsible for the coronavirus disease 2019 (COVID-19). The high rate of mutation of this virus is associated with a quick emergence of new viral variants that have been rapidly spreading worldwide. [...] Read more.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent responsible for the coronavirus disease 2019 (COVID-19). The high rate of mutation of this virus is associated with a quick emergence of new viral variants that have been rapidly spreading worldwide. Several mutations have been documented in the receptor-binding domain (RBD) of the viral spike protein that increases the interaction between SARS-CoV-2 and its cellular receptor, the angiotensin-converting enzyme 2 (ACE2). Mutations in the spike can increase the viral spread rate, disease severity, and the ability of the virus to evade either the immune protective responses, monoclonal antibody treatments, or the efficacy of current licensed vaccines. This review aimed to highlight the functional virus classification used by the World Health Organization (WHO), Phylogenetic Assignment of Named Global Outbreak (PANGO), Global Initiative on Sharing All Influenza Data (GISAID), and Nextstrain, an open-source project to harness the scientific and public health potential of pathogen genome data, the chronological emergence of viral variants of concern (VOCs) and variants of interest (VOIs), the major findings related to the rate of spread, and the mutations in the spike protein that are involved in the evasion of the host immune responses elicited by prior SARS-CoV-2 infections and by the protection induced by vaccination. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

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34 pages, 3120 KiB

Open AccessReview

Implications of the Immune Polymorphisms of the Host and the Genetic Variability of SARS-CoV-2 in the Development of COVID-19

by Jesús Zepeda-Cervantes, Daniel Martínez-Flores, Josué Orlando Ramírez-Jarquín, Ángeles C. Tecalco-Cruz, Noé Santiago Alavez-Pérez, Luis Vaca and Rosa Elena Sarmiento-Silva

Viruses 2022, 14(1), 94; https://0-doi-org.brum.beds.ac.uk/10.3390/v14010094 - 06 Jan 2022

Cited by 7 | Viewed by 4629

Abstract

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current pandemic affecting almost all countries in the world. SARS-CoV-2 is the agent responsible for coronavirus disease 19 (COVID-19), which has claimed millions of lives around the world. In most patients, SARS-CoV-2 [...] Read more.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current pandemic affecting almost all countries in the world. SARS-CoV-2 is the agent responsible for coronavirus disease 19 (COVID-19), which has claimed millions of lives around the world. In most patients, SARS-CoV-2 infection does not cause clinical signs. However, some infected people develop symptoms, which include loss of smell or taste, fever, dry cough, headache, severe pneumonia, as well as coagulation disorders. The aim of this work is to report genetic factors of SARS-CoV-2 and host-associated to severe COVID-19, placing special emphasis on the viral entry and molecules of the immune system involved with viral infection. Besides this, we analyze SARS-CoV-2 variants and their structural characteristics related to the binding to polymorphic angiotensin-converting enzyme type 2 (ACE2). Additionally, we also review other polymorphisms as well as some epigenetic factors involved in the immunopathogenesis of COVID-19. These factors and viral variability could explain the increment of infection rate and/or in the development of severe COVID-19. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

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9 pages, 257 KiB

Open AccessReview

¹⁸F-FDG-PET Imaging for Post-COVID-19 Brain and Skeletal Muscle Alterations

by Thorsten Rudroff, Craig D. Workman and Laura L. Boles Ponto

Viruses 2021, 13(11), 2283; https://0-doi-org.brum.beds.ac.uk/10.3390/v13112283 - 15 Nov 2021

Cited by 30 | Viewed by 3917

Abstract

Scientific evidence concerning the subacute and long-term effects of coronavirus disease 2019 (COVID-19) is on the rise. It has been established that infection by serious acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a systemic process that involves multiple organs. The complications and long-term [...] Read more.

Scientific evidence concerning the subacute and long-term effects of coronavirus disease 2019 (COVID-19) is on the rise. It has been established that infection by serious acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a systemic process that involves multiple organs. The complications and long-term consequences of COVID-19 are diverse and patients need a multidisciplinary treatment approach in the acute and post-acute stages of the disease. A significant proportion of COVID-19 patients experience neurological manifestations, some enduring for several months post-recovery. However, brain and skeletal muscle changes resultant from SARS CoV-2 infection remain largely unknown. Here, we provide a brief overview of the current knowledge, and usefulness, of [¹⁸F]fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) to investigate brain and skeletal muscles changes in Post-COVID-19 patients with persistent symptoms. Furthermore, a brief discussion of future ¹⁸F-FDG-PET/CT applications that might advance the current knowledge of the pathogenesis of post-COVID-19 is also provided. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

Other

Jump to: Research, Review

7 pages, 2319 KiB

Open AccessBrief Report

Lipid Accumulation in Host Cells Promotes SARS-CoV-2 Replication

by Tatjana Seitz, Christian Setz, Pia Rauch, Ulrich Schubert and Claus Hellerbrand

Viruses 2023, 15(4), 1026; https://0-doi-org.brum.beds.ac.uk/10.3390/v15041026 - 21 Apr 2023

Cited by 2 | Viewed by 1646

Abstract

Coronavirus disease-19 (COVID-19) is still affecting the lives of people around the globe and remains a major public health threat. Lipid levels in the host cells have been shown to promote SARS-CoV-2 replication, and since the start of COVID-19 pandemic, several studies have [...] Read more.

Coronavirus disease-19 (COVID-19) is still affecting the lives of people around the globe and remains a major public health threat. Lipid levels in the host cells have been shown to promote SARS-CoV-2 replication, and since the start of COVID-19 pandemic, several studies have linked obesity and other components of the metabolic syndrome with severity of illness, as well as mortality in patients with COVID-19. The aim of this study was to obtain insights into the pathophysiological mechanisms of these associations. First, we established an in vitro model simulating high fatty acid levels and showed that this situation induced the uptake of fatty acids and triglyceride accumulation in human Calu-3 lung cells. Importantly, we found that lipid accumulation significantly enhanced the replication of SARS-CoV-2 Wuhan type or the variant of concern, Delta, in Calu-3 cells. In summary, these findings indicate that hyperlipidemia as found in patients with obesity promotes viral replication and herewith the disease course of COVID-19. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

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7 pages, 1326 KiB

Open AccessBrief Report

Reduced Seasonal Coronavirus Antibody Responses in Children Following COVID-19 Mitigation Measures, The Netherlands

by Reina S. Sikkema, Erwin de Bruin, Christian Ramakers, Robbert Bentvelsen, Wentao Li, Berend-Jan Bosch, Brenda Westerhuis, Bart Haagmans, Marion P. G. Koopmans and Pieter L. A. Fraaij

Viruses 2023, 15(1), 212; https://0-doi-org.brum.beds.ac.uk/10.3390/v15010212 - 12 Jan 2023

Viewed by 1625

Abstract

SARS-CoV-2 prevention and control measures did not only impact SARS-CoV-2 circulation, but also the timing and prevalence of other seasonal respiratory viruses. Especially in children, information on exposure and infections to seasonal coronaviruses as well as SARS-CoV-2 in the first year of the [...] Read more.

SARS-CoV-2 prevention and control measures did not only impact SARS-CoV-2 circulation, but also the timing and prevalence of other seasonal respiratory viruses. Especially in children, information on exposure and infections to seasonal coronaviruses as well as SARS-CoV-2 in the first year of the pandemic is largely lacking. Therefore, we set up a one-year serological survey in a large tertiary hospital in the Netherlands. We show that seasonal coronavirus seroprevalence significantly decreased in 2021 in children less than one year, most likely due to COVID-19 control measures. The SARS-CoV-2 seroprevalence in children and adolescents increased from 0.4% to 11.3%, the highest in adolescents. This implies higher exposure rates in adolescents as compared to the general population (>18 years old). It is clear that there have been significant changes in the circulation and subsequent immunity against most respiratory pathogens as a result of the mitigation measures. The implications on shorter as well as longer term are still largely unknown, but the impact of the SARS-CoV-2 pandemic and subsequent control measures will continue to affect the dynamics of other pathogens. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

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18 pages, 3326 KiB

Open AccessBrief Report

Evolutionary Signals in Coronaviral Structural Proteins Suggest Possible Complex Mechanisms of Post-Translational Regulation in SARS-CoV-2 Virus

by Ramiro Garza-Domínguez and Francisco Torres-Quiroz

Viruses 2022, 14(11), 2469; https://0-doi-org.brum.beds.ac.uk/10.3390/v14112469 - 08 Nov 2022

Viewed by 1344

Abstract

Post-translational regulation of proteins has emerged as a central topic of research in the field of functional proteomics. Post-translational modifications (PTMs) dynamically control the activities of proteins and are involved in a wide range of biological processes. Crosstalk between different types of PTMs [...] Read more.

Post-translational regulation of proteins has emerged as a central topic of research in the field of functional proteomics. Post-translational modifications (PTMs) dynamically control the activities of proteins and are involved in a wide range of biological processes. Crosstalk between different types of PTMs represents a key mechanism of regulation and signaling. Due to the current pandemic of the novel and dangerous SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) virus, here we present an in silico analysis of different types of PTMs in structural proteins of coronaviruses. A dataset of PTM sites was studied at three levels: conservation analysis, mutational analysis and crosstalk analysis. We identified two sets of PTMs which could have important functional roles in the regulation of the structural proteins of coronaviruses. Additionally, we found seven interesting signals of potential crosstalk events. These results reveal a higher level of complexity in the mechanisms of post-translational regulation of coronaviral proteins and provide new insights into the adaptation process of the SARS-CoV-2 virus. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

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21 pages, 1641 KiB

Open AccessSystematic Review

SARS-CoV-2 Vaccines during Pregnancy and Breastfeeding: A Systematic Review of Maternal and Neonatal Outcomes

by Domenico Umberto De Rose, Guglielmo Salvatori, Andrea Dotta and Cinzia Auriti

Viruses 2022, 14(3), 539; https://0-doi-org.brum.beds.ac.uk/10.3390/v14030539 - 05 Mar 2022

Cited by 23 | Viewed by 5577

Abstract

(1) Objective: This systematic review summarizes current knowledges about maternal and neonatal outcomes following COVID-19 vaccination during pregnancy and breastfeeding. (2) Study design: PubMed, Cochrane Library, and the Education Resources Information Center (ERIC) were searched up to 27 October 2021. The primary [...] Read more.

(1) Objective: This systematic review summarizes current knowledges about maternal and neonatal outcomes following COVID-19 vaccination during pregnancy and breastfeeding. (2) Study design: PubMed, Cochrane Library, and the Education Resources Information Center (ERIC) were searched up to 27 October 2021. The primary outcome was to estimate how many pregnant and lactating women were reported to be vaccinated and had available maternal and neonatal outcomes. (3) Results: Forty-five studies sourcing data of 74,908 pregnant women and 5098 lactating women who received COVID-19 vaccination were considered as eligible. No major side-effects were reported, especially during the second and third trimester of pregnancy and during breastfeeding. Conversely, available studies revealed that infants received specific SARS-CoV-2 antibodies after maternal vaccination. (4) Conclusions: Vaccination against the SARS-CoV-2 virus should be recommended for pregnant women, after the pros and cons have been adequately explained. In particular, given the still limited evidence and considering that fever during the first months of gestation increases the possibility of congenital anomalies, they should be carefully counseled. The same considerations apply to breastfeeding women, also considering the immune responses that mRNA vaccines can generate in their human milk. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

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7 pages, 1664 KiB

Open AccessBrief Report

In-Silico Analysis of Monoclonal Antibodies against SARS-CoV-2 Omicron

by Ye-Fan Hu, Jing-Chu Hu, Hin Chu, Thomas Yau, Bao-Zhong Zhang and Jian-Dong Huang

Viruses 2022, 14(2), 390; https://0-doi-org.brum.beds.ac.uk/10.3390/v14020390 - 14 Feb 2022

Cited by 9 | Viewed by 2860

Abstract

Omicron was designated by the WHO as a VOC on 26 November 2021, only 4 days after its sequence was first submitted. However, the impact of Omicron on current antibodies and vaccines remains unknown and evaluations are still a few weeks away. We [...] Read more.

Omicron was designated by the WHO as a VOC on 26 November 2021, only 4 days after its sequence was first submitted. However, the impact of Omicron on current antibodies and vaccines remains unknown and evaluations are still a few weeks away. We analysed the mutations in the Omicron variant against epitopes. In our database, 132 epitopes of the 120 antibodies are classified into five groups, namely NTD, RBD-1, RBD-2, RBD-3, and RBD-4. The Omicron mutations impact all epitopes in NTD, RBD-1, RBD-2, and RBD-3, with no antibody epitopes spared by these mutations. Only four out of 120 antibodies may confer full resistance to mutations in the Omicron spike, since all antibodies in these three groups contain one or more epitopes that are affected by these mutations. Of all antibodies under EUA, the neutralisation potential of Etesevimab, Bamlanivimab, Casirivimab, Imdevima, Cilgavimab, Tixagevimab, Sotrovimab, and Regdanvimab might be dampened to varying degrees. Our analysis suggests the impact of Omicron on current therapeutic antibodies by the Omicron spike mutations may also apply to current COVID-19 vaccines. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

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