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Viruses
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Vaccines and Therapeutics against Coronaviruses
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Vaccines and Therapeutics against Coronaviruses

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "SARS-CoV-2 and COVID-19".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 347774

Special Issue Editors

Dr. Kenneth Lundstrom

E-Mail
Guest Editor
PanTherapeutics, Rue des Remparts 4, CH-1095 Lutry, Switzerland
Interests: viral gene therapy; viral vaccines; gene expression using viral vectors; structural biology; epigenetics; nutrigenomics
Special Issues, Collections and Topics in MDPI journals
Dr. Alaa A. A. Aljabali

E-Mail Website
Guest Editor
Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Yarmouk University, Irbid 21163, P. O. BOX 566, Jordan
Interests: viruses; virus-like particles (VLPs); chemical engineering; biological nanoparticles; immune therapy

Special Issue Information

Dear Colleagues,

The current COVID-19 pandemic has caused unprecedented devastation to health and the economy around the world, and is expected to continue for an unforeseen time into the future due to the lack of existing antiviral drugs and vaccines. In a unique cooperation between academic institutions, pharmaceutical and biotech enterprises, and governmental organizations, the research and development of vaccines and therapeutics against COVID-19 is occurring at a level never seen before. This research has generated plenty of new information on COVID-19 as well as SARS-CoV-2, responsible for the pandemic, as illustrated by the 74,417 publications found in PubMed when using the search term “COVID-19”. Today, some drugs have demonstrated specific efficacy in the treatment of seriously ill COVID-19 patients, and two vaccine candidates have shown promising primary results in phase III clinical trials. However, we have not yet conquered the disease, and research and development on vaccines and therapeutics should continue at maximum speed and effort. Therefore, it is time to welcome contributions to this Special Issue of Viruses, “Vaccines and Therapeutics against Coronaviruses”. The aim is to provide comprehensive information on all aspects of coronavirus research and development on vaccines and therapeutics. To achieve this goal, it is essential to understand the biology and virology of coronaviruses. Application of bioinformatics, mathematics, genomics, structural biology, and modeling is an essential part of developing safe and efficient vaccines and therapeutics. We also need to develop the best tools and strategies possible for vaccine and drug delivery systems. Epidemiology and diagnostics are also important areas to discuss. Finally, another aim is to outline the strategy for confronting future emerging outbreaks caused by coronaviruses or some other novel virus. We cordially invite you to contribute to the Special Issue “Vaccines and Therapeutics against Coronaviruses” to advance our knowledge on coronaviruses and to discover the means to overcome the pandemic together.

Dr. Kenneth Lundstrom
Dr. Alaa A. A. Aljabali
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • SARS-CoV-2
  • COVID-19
  • antivirals
  • vaccines
  • therapeutics

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Published Papers (27 papers)

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Editorial

Jump to: Research, Review, Other

5 pages, 205 KiB  
Editorial
COVID-19 in 2021
by Kenneth Lundstrom and Alaa A. A. Aljabali
Viruses 2021, 13(10), 2098; https://0-doi-org.brum.beds.ac.uk/10.3390/v13102098 - 18 Oct 2021
Cited by 2 | Viewed by 2508
Abstract
The Special Issue on Vaccines and Therapeutics against Coronaviruses, which was launched in early 2021, has attracted the scientific community at large, and more than 20 manuscripts have been accepted for publication.[...] Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)

Research

Jump to: Editorial, Review, Other

8 pages, 2000 KiB  
Article
Epigallocatechin Gallate (EGCG), a Green Tea Polyphenol, Reduces Coronavirus Replication in a Mouse Model
by Rackhyun Park, Minsu Jang, Yea-In Park, Yeonjeong Park, Woochul Jung, Jayhyun Park and Junsoo Park
Viruses 2021, 13(12), 2533; https://0-doi-org.brum.beds.ac.uk/10.3390/v13122533 - 17 Dec 2021
Cited by 28 | Viewed by 5327
Abstract
The COVID-19 pandemic has resulted in a huge number of deaths from 2020 to 2021; however, effective antiviral drugs against SARS-CoV-2 are currently under development. Recent studies have demonstrated that green tea polyphenols, particularly EGCG, inhibit coronavirus enzymes as well as coronavirus replication [...] Read more.
The COVID-19 pandemic has resulted in a huge number of deaths from 2020 to 2021; however, effective antiviral drugs against SARS-CoV-2 are currently under development. Recent studies have demonstrated that green tea polyphenols, particularly EGCG, inhibit coronavirus enzymes as well as coronavirus replication in vitro. Herein, we examined the inhibitory effect of green tea polyphenols on coronavirus replication in a mouse model. We used epigallocatechin gallate (EGCG) and green tea polyphenols containing more than 60% catechin (GTP60) and human coronavirus OC43 (HCoV-OC43) as a surrogate for SARS-CoV-2. Scanning electron microscopy analysis results showed that HCoV-OC43 infection resulted in virion particle production in infected cells. EGCG and GTP60 treatment reduced coronavirus protein and virus production in the cells. Finally, EGCG- and GTP60-fed mice exhibited reduced levels of coronavirus RNA in mouse lungs. These results demonstrate that green tea polyphenol treatment is effective in decreasing the level of coronavirus in vivo. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
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15 pages, 1313 KiB  
Article
Global Prevalence of Adaptive and Prolonged Infections’ Mutations in the Receptor-Binding Domain of the SARS-CoV-2 Spike Protein
by Johan Lennerstrand and Navaneethan Palanisamy
Viruses 2021, 13(10), 1974; https://0-doi-org.brum.beds.ac.uk/10.3390/v13101974 - 30 Sep 2021
Cited by 9 | Viewed by 3142
Abstract
Several vaccines with varying efficacies have been developed and are currently administered globally to minimize the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite having an RNA-dependent RNA polymerase with a proofreading activity, new variants of SARS-CoV-2 are on the rise [...] Read more.
Several vaccines with varying efficacies have been developed and are currently administered globally to minimize the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite having an RNA-dependent RNA polymerase with a proofreading activity, new variants of SARS-CoV-2 are on the rise periodically. Some of the mutations in these variants, especially mutations on the spike protein, aid the virus in transmission, infectivity and host immune evasion. Further, these mutations also reduce the effectiveness of some of the current vaccines and monoclonal antibodies (mAbs). In the present study, using the available 984,769 SARS-CoV-2 nucleotide sequences on the NCBI database from the end of 2019 till 28 July 2021, we have estimated the global prevalence of so-called ‘adaptive mutations’ and ‘mutations identified in the prolonged infections’, in the receptor-binding domain (RBD) of the spike (S) protein. Irrespective of the geographical region, in the case of the adaptive mutations, N501Y (48.38%) was found to be the dominant mutation followed by L452R (17.52%), T478K (14.31%), E484K (4.69%), S477N (3.29%), K417T (1.64%), N439K (0.7%) and S494P (0.7%). Other mutations were found to be less prevalent (less than 0.7%). Since the last two months, there has been a massive increase of L452R and T478K mutations (delta variant) in certain areas. In the case of prolonged infections’ mutations (long-term SARS-CoV-2 infections), V483A (0.009%) was found to be dominant followed by Q493R (0.009%), while other mutations were found in less than 0.007% of the studied sequences. The data obtained in this study will aid in the development of better infection control policies, thereby curbing the spread of this virus. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
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26 pages, 7331 KiB  
Article
Potential Molecular Mechanisms of Rare Anti-Tumor Immune Response by SARS-CoV-2 in Isolated Cases of Lymphomas
by Debmalya Barh, Sandeep Tiwari, Lucas Gabriel Rodrigues Gomes, Marianna E. Weener, Khalid J. Alzahrani, Khalaf F. Alsharif, Alaa A. A. Aljabali, Murtaza M. Tambuwala, Kenneth Lundstrom, Sk. Sarif Hassan, Ángel Serrano-Aroca, Kazuo Takayama, Preetam Ghosh, Elrashdy M. Redwan, Bruno Silva Andrade, Siomar de Castro Soares, Vasco Azevedo and Vladimir N. Uversky
Viruses 2021, 13(10), 1927; https://0-doi-org.brum.beds.ac.uk/10.3390/v13101927 - 25 Sep 2021
Cited by 11 | Viewed by 4078
Abstract
Recently, two cases of complete remission of classical Hodgkin lymphoma (cHL) and follicular lymphoma (FL) after SARS-CoV-2 infection were reported. However, the precise molecular mechanism of this rare event is yet to be understood. Here, we hypothesize a potential anti-tumor immune response of [...] Read more.
Recently, two cases of complete remission of classical Hodgkin lymphoma (cHL) and follicular lymphoma (FL) after SARS-CoV-2 infection were reported. However, the precise molecular mechanism of this rare event is yet to be understood. Here, we hypothesize a potential anti-tumor immune response of SARS-CoV-2 and based on a computational approach show that: (i) SARS-CoV-2 Spike-RBD may bind to the extracellular domains of CD15, CD27, CD45, and CD152 receptors of cHL or FL and may directly inhibit cell proliferation. (ii) Alternately, upon internalization after binding to these CD molecules, the SARS-CoV-2 membrane (M) protein and ORF3a may bind to gamma-tubulin complex component 3 (GCP3) at its tubulin gamma-1 chain (TUBG1) binding site. (iii) The M protein may also interact with TUBG1, blocking its binding to GCP3. (iv) Both the M and ORF3a proteins may render the GCP2-GCP3 lateral binding where the M protein possibly interacts with GCP2 at its GCP3 binding site and the ORF3a protein to GCP3 at its GCP2 interacting residues. (v) Interactions of the M and ORF3a proteins with these gamma-tubulin ring complex components potentially block the initial process of microtubule nucleation, leading to cell-cycle arrest and apoptosis. (vi) The Spike-RBD may also interact with and block PD-1 signaling similar to pembrolizumab and nivolumab- like monoclonal antibodies and may induce B-cell apoptosis and remission. (vii) Finally, the TRADD interacting “PVQLSY” motif of Epstein-Barr virus LMP-1, that is responsible for NF-kB mediated oncogenesis, potentially interacts with SARS-CoV-2 Mpro, NSP7, NSP10, and spike (S) proteins, and may inhibit the LMP-1 mediated cell proliferation. Taken together, our results suggest a possible therapeutic potential of SARS-CoV-2 in lymphoproliferative disorders. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
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12 pages, 2237 KiB  
Article
Turmeric Root and Its Bioactive Ingredient Curcumin Effectively Neutralize SARS-CoV-2 In Vitro
by Maren Bormann, Mira Alt, Leonie Schipper, Lukas van de Sand, Vu Thuy Khanh Le-Trilling, Lydia Rink, Natalie Heinen, Rabea Julia Madel, Mona Otte, Korbinian Wuensch, Christiane Silke Heilingloh, Thorsten Mueller, Ulf Dittmer, Carina Elsner, Stephanie Pfaender, Mirko Trilling, Oliver Witzke and Adalbert Krawczyk
Viruses 2021, 13(10), 1914; https://0-doi-org.brum.beds.ac.uk/10.3390/v13101914 - 23 Sep 2021
Cited by 35 | Viewed by 38811
Abstract
Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19). The availability of effective and well-tolerated antiviral drugs for the treatment of COVID-19 patients is still very limited. Traditional herbal medicines elicit antiviral activity against [...] Read more.
Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19). The availability of effective and well-tolerated antiviral drugs for the treatment of COVID-19 patients is still very limited. Traditional herbal medicines elicit antiviral activity against various viruses and might therefore represent a promising option for the complementary treatment of COVID-19 patients. The application of turmeric root in herbal medicine has a very long history. Its bioactive ingredient curcumin shows a broad-spectrum antimicrobial activity. In the present study, we investigated the antiviral activity of aqueous turmeric root extract, the dissolved content of a curcumin-containing nutritional supplement capsule, and pure curcumin against SARS-CoV-2. Turmeric root extract, dissolved turmeric capsule content, and pure curcumin effectively neutralized SARS-CoV-2 at subtoxic concentrations in Vero E6 and human Calu-3 cells. Furthermore, curcumin treatment significantly reduced SARS-CoV-2 RNA levels in cell culture supernatants. Our data uncover curcumin as a promising compound for complementary COVID-19 treatment. Curcumin concentrations contained in turmeric root or capsules used as nutritional supplements completely neutralized SARS-CoV-2 in vitro. Our data argue in favor of appropriate and carefully monitored clinical studies that vigorously test the effectiveness of complementary treatment of COVID-19 patients with curcumin-containing products. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
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13 pages, 1875 KiB  
Article
All-Trans Retinoic Acid Exhibits Antiviral Effect against SARS-CoV-2 by Inhibiting 3CLpro Activity
by Takeshi Morita, Kei Miyakawa, Sundararaj Stanleyraj Jeremiah, Yutaro Yamaoka, Mitsuru Sada, Tomoko Kuniyoshi, Jinwei Yang, Hirokazu Kimura and Akihide Ryo
Viruses 2021, 13(8), 1669; https://0-doi-org.brum.beds.ac.uk/10.3390/v13081669 - 23 Aug 2021
Cited by 20 | Viewed by 3322
Abstract
The pandemic of COVID-19 caused by SARS-CoV-2 continues to spread despite the global efforts taken to control it. The 3C-like protease (3CLpro), the major protease of SARS-CoV-2, is one of the most interesting targets for antiviral drug development because it is highly conserved [...] Read more.
The pandemic of COVID-19 caused by SARS-CoV-2 continues to spread despite the global efforts taken to control it. The 3C-like protease (3CLpro), the major protease of SARS-CoV-2, is one of the most interesting targets for antiviral drug development because it is highly conserved among SARS-CoVs and plays an important role in viral replication. Herein, we developed high throughput screening for SARS-CoV-2 3CLpro inhibitor based on AlphaScreen. We screened 91 natural product compounds and found that all-trans retinoic acid (ATRA), an FDA-approved drug, inhibited 3CLpro activity. The 3CLpro inhibitory effect of ATRA was confirmed in vitro by both immunoblotting and AlphaScreen with a 50% inhibition concentration (IC50) of 24.7 ± 1.65 µM. ATRA inhibited the replication of SARS-CoV-2 in VeroE6/TMPRSS2 and Calu-3 cells, with IC50 = 2.69 ± 0.09 µM in the former and 0.82 ± 0.01 µM in the latter. Further, we showed the anti-SARS-CoV-2 effect of ATRA on the currently circulating variants of concern (VOC); alpha, beta, gamma, and delta. These results suggest that ATRA may be considered as a potential therapeutic agent against SARS-CoV-2. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
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8 pages, 944 KiB  
Article
Emergence of E484K Mutation Following Bamlanivimab Monotherapy among High-Risk Patients Infected with the Alpha Variant of SARS-CoV-2
by Nathan Peiffer-Smadja, Antoine Bridier-Nahmias, Valentine Marie Ferré, Charlotte Charpentier, Mathilde Garé, Christophe Rioux, Aude Allemand, Philippa Lavallée, Jade Ghosn, Laura Kramer, Diane Descamps, Yazdan Yazdanpanah and Benoit Visseaux
Viruses 2021, 13(8), 1642; https://0-doi-org.brum.beds.ac.uk/10.3390/v13081642 - 19 Aug 2021
Cited by 31 | Viewed by 2782
Abstract
An Emergency Use Authorization was issued in the United States and in Europe for a monoclonal antibody monotherapy to prevent severe COVID-19 in high-risk patients. This study aimed to assess the risk of emergence of mutations following treatment with a single monoclonal antibody. [...] Read more.
An Emergency Use Authorization was issued in the United States and in Europe for a monoclonal antibody monotherapy to prevent severe COVID-19 in high-risk patients. This study aimed to assess the risk of emergence of mutations following treatment with a single monoclonal antibody. Bamlanivimab was administered at a single dose of 700 mg in a one-hour IV injection in a referral center for the management of COVID-19 in France. Patients were closely monitored clinically and virologically with nasopharyngeal RT-PCR and viral whole genome sequencing. Six patients were treated for a nosocomial SARS-CoV-2 infection, all males, with a median age of 65 years and multiple comorbidities. All patients were infected with a B.1.1.7 variant, which was the most frequent variant in France at the time, and no patients had E484 mutations at baseline. Bamlanivimab was infused in the six patients within 4 days of the COVID-19 diagnosis. Four patients had a favorable outcome, one died of complications unrelated to COVID-19 or bamlanivimab, and one kidney transplant patient treated with belatacept died from severe COVID-19 more than 40 days after bamlanivimab administration. Virologically, four patients cleared nasopharyngeal viral shedding within one month after infusion, while two presented prolonged viral excretion for more than 40 days. The emergence of E484K mutants was observed in five out of six patients, and the last patient presented a Q496R mutation potentially associated with resistance. CONCLUSIONS: These results show a high risk of emergence of resistance mutants in COVID-19 patients treated with monoclonal antibody monotherapy. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
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11 pages, 1087 KiB  
Article
Effects of a Single Dose of Ivermectin on Viral and Clinical Outcomes in Asymptomatic SARS-CoV-2 Infected Subjects: A Pilot Clinical Trial in Lebanon
by Ali A. Samaha, Hussein Mouawia, Mirna Fawaz, Hamad Hassan, Ali Salami, Ali Al Bazzal, Hamid Bou Saab, Mohamed Al-Wakeel, Ahmad Alsaabi, Mohamad Chouman, Mahmoud Al Moussawi, Hassan Ayoub, Ali Raad, Ola Hajjeh, Ali H. Eid and Houssam Raad
Viruses 2021, 13(6), 989; https://0-doi-org.brum.beds.ac.uk/10.3390/v13060989 - 26 May 2021
Cited by 31 | Viewed by 65484 | Retraction
Abstract
Objective: This study was designed to determine the efficacy of ivermectin, an FDA-approved drug, in producing clinical benefits and decreasing the viral load of SARS-CoV-2 among asymptomatic subjects that tested positive for this virus in Lebanon. Methods: A randomized controlled trial was conducted [...] Read more.
Objective: This study was designed to determine the efficacy of ivermectin, an FDA-approved drug, in producing clinical benefits and decreasing the viral load of SARS-CoV-2 among asymptomatic subjects that tested positive for this virus in Lebanon. Methods: A randomized controlled trial was conducted in 100 asymptomatic Lebanese subjects that have tested positive for SARS-CoV2. Fifty patients received standard preventive treatment, mainly supplements, and the experimental group received a single dose (according to body weight) of ivermectin, in addition to the same supplements the control group received. Results: There was no significant difference (p = 0.06) between Ct-values of the two groups before the regimen was started (day zero), indicating that subjects in both groups had similar viral loads. At 72 h after the regimen started, the increase in Ct-values was dramatically higher in the ivermectin than in the control group. In the ivermectin group, Ct increased from 15.13 ± 2.07 (day zero) to 30.14 ± 6.22 (day three; mean ± SD), compared to the control group, where the Ct values increased only from 14.20 ± 2.48 (day zero) to 18.96 ± 3.26 (day three; mean ± SD). Moreover, more subjects in the control group developed clinical symptoms. Three individuals (6%) required hospitalization, compared to the ivermectin group (0%). Conclusion: Ivermectin appears to be efficacious in providing clinical benefits in a randomized treatment of asymptomatic SARS-CoV-2-positive subjects, effectively resulting in fewer symptoms, lower viral load and reduced hospital admissions. However, larger-scale trials are warranted for this conclusion to be further cemented. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
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18 pages, 6654 KiB  
Article
Exploring the Role of Glycans in the Interaction of SARS-CoV-2 RBD and Human Receptor ACE2
by Kien Nguyen, Srirupa Chakraborty, Rachael A. Mansbach, Bette Korber and Sandrasegaram Gnanakaran
Viruses 2021, 13(5), 927; https://0-doi-org.brum.beds.ac.uk/10.3390/v13050927 - 17 May 2021
Cited by 24 | Viewed by 3652
Abstract
COVID-19 is a highly infectious respiratory disease caused by the novel coronavirus SARS-CoV-2. It has become a global pandemic and its frequent mutations may pose new challenges for vaccine design. During viral infection, the Spike RBD of SARS-CoV-2 binds the human host cell [...] Read more.
COVID-19 is a highly infectious respiratory disease caused by the novel coronavirus SARS-CoV-2. It has become a global pandemic and its frequent mutations may pose new challenges for vaccine design. During viral infection, the Spike RBD of SARS-CoV-2 binds the human host cell receptor ACE2, enabling the virus to enter the host cell. Both the Spike and ACE2 are densely glycosylated, and it is unclear how distinctive glycan types may modulate the interaction of RBD and ACE2. Detailed understanding of these determinants is key for the development of novel therapeutic strategies. To this end, we perform extensive all-atom simulations of the (i) RBD-ACE2 complex without glycans, (ii) RBD-ACE2 with oligomannose MAN9 glycans in ACE2, and (iii) RBD-ACE2 with complex FA2 glycans in ACE2. These simulations identify the key residues at the RBD-ACE2 interface that form contacts with higher probabilities, thus providing a quantitative evaluation that complements recent structural studies. Notably, we find that this RBD-ACE2 contact signature is not altered by the presence of different glycoforms, suggesting that RBD-ACE2 interaction is robust. Applying our simulated results, we illustrate how the recently prevalent N501Y mutation may alter specific interactions with host ACE2 that facilitate the virus-host binding. Furthermore, our simulations reveal how the glycan on Asn90 of ACE2 can play a distinct role in the binding and unbinding of RBD. Finally, an energetics analysis shows that MAN9 glycans on ACE2 decrease RBD-ACE2 affinity, while FA2 glycans lead to enhanced binding of the complex. Together, our results provide a more comprehensive picture of the detailed interplay between virus and human receptor, which is much needed for the discovery of effective treatments that aim at modulating the physical-chemical properties of this virus. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
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14 pages, 4346 KiB  
Article
Screening of FDA-Approved Drugs Using a MERS-CoV Clinical Isolate from South Korea Identifies Potential Therapeutic Options for COVID-19
by Meehyun Ko, So Young Chang, Soo Young Byun, Aleksandr Ianevski, Inhee Choi, Anne-Laure Pham Hung d’Alexandry d’Orengiani, Erlend Ravlo, Wei Wang, Magnar Bjørås, Denis E. Kainov, David Shum, Ji-Young Min and Marc P. Windisch
Viruses 2021, 13(4), 651; https://0-doi-org.brum.beds.ac.uk/10.3390/v13040651 - 09 Apr 2021
Cited by 60 | Viewed by 4813
Abstract
Therapeutic options for coronaviruses remain limited. To address this unmet medical need, we screened 5406 compounds, including United States Food and Drug Administration (FDA)-approved drugs and bioactives, for activity against a South Korean Middle East respiratory syndrome coronavirus (MERS-CoV) clinical isolate. Among 221 [...] Read more.
Therapeutic options for coronaviruses remain limited. To address this unmet medical need, we screened 5406 compounds, including United States Food and Drug Administration (FDA)-approved drugs and bioactives, for activity against a South Korean Middle East respiratory syndrome coronavirus (MERS-CoV) clinical isolate. Among 221 identified hits, 54 had therapeutic indexes (TI) greater than 6, representing effective drugs. The time-of-addition studies with selected drugs demonstrated eight and four FDA-approved drugs which acted on the early and late stages of the viral life cycle, respectively. Confirmed hits included several cardiotonic agents (TI > 100), atovaquone, an anti-malarial (TI > 34), and ciclesonide, an inhalable corticosteroid (TI > 6). Furthermore, utilizing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we tested combinations of remdesivir with selected drugs in Vero-E6 and Calu-3 cells, in lung organoids, and identified ciclesonide, nelfinavir, and camostat to be at least additive in vitro. Our results identify potential therapeutic options for MERS-CoV infections, and provide a basis to treat coronavirus disease 2019 (COVID-19) and other coronavirus-related illnesses. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
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10 pages, 1716 KiB  
Article
Glycyrrhizin Effectively Inhibits SARS-CoV-2 Replication by Inhibiting the Viral Main Protease
by Lukas van de Sand, Maren Bormann, Mira Alt, Leonie Schipper, Christiane Silke Heilingloh, Eike Steinmann, Daniel Todt, Ulf Dittmer, Carina Elsner, Oliver Witzke and Adalbert Krawczyk
Viruses 2021, 13(4), 609; https://0-doi-org.brum.beds.ac.uk/10.3390/v13040609 - 02 Apr 2021
Cited by 118 | Viewed by 9837
Abstract
The outbreak of SARS-CoV-2 developed into a global pandemic affecting millions of people worldwide. Despite one year of intensive research, the current treatment options for SARS-CoV-2 infected people are still limited. Clearly, novel antiviral compounds for the treatment of SARS-CoV-2 infected patients are [...] Read more.
The outbreak of SARS-CoV-2 developed into a global pandemic affecting millions of people worldwide. Despite one year of intensive research, the current treatment options for SARS-CoV-2 infected people are still limited. Clearly, novel antiviral compounds for the treatment of SARS-CoV-2 infected patients are still urgently needed. Complementary medicine is used along with standard medical treatment and accessible to a vast majority of people worldwide. Natural products with antiviral activity may contribute to improve the overall condition of SARS-CoV-2 infected individuals. In the present study, we investigated the antiviral activity of glycyrrhizin, the primary active ingredient of the licorice root, against SARS-CoV-2. We demonstrated that glycyrrhizin potently inhibits SARS-CoV-2 replication in vitro. Furthermore, we uncovered the underlying mechanism and showed that glycyrrhizin blocks the viral replication by inhibiting the viral main protease Mpro that is essential for viral replication. Our data indicate that the consumption of glycyrrhizin-containing products such as licorice root tea of black licorice may be of great benefit for SARS-CoV-2 infected people. Furthermore, glycyrrhizin is a good candidate for further investigation for clinical use to treat COVID-19 patients. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
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11 pages, 1045 KiB  
Article
In Vitro Assessment of the Antiviral Activity of Ketotifen, Indomethacin and Naproxen, Alone and in Combination, against SARS-CoV-2
by Pantea Kiani, Andrew Scholey, Thomas A. Dahl, Lauren McMann, Jacqueline M. Iversen and Joris C. Verster
Viruses 2021, 13(4), 558; https://0-doi-org.brum.beds.ac.uk/10.3390/v13040558 - 26 Mar 2021
Cited by 23 | Viewed by 6192
Abstract
The 2019 coronavirus infectious disease (COVID-19) is caused by infection with the new severe acute respiratory syndrome coronavirus (SARS-CoV-2). Currently, the treatment options for COVID-19 are limited. The purpose of the experiments presented here was to investigate the effectiveness of ketotifen, naproxen and [...] Read more.
The 2019 coronavirus infectious disease (COVID-19) is caused by infection with the new severe acute respiratory syndrome coronavirus (SARS-CoV-2). Currently, the treatment options for COVID-19 are limited. The purpose of the experiments presented here was to investigate the effectiveness of ketotifen, naproxen and indomethacin, alone or in combination, in reducing SARS-CoV-2 replication. In addition, the cytotoxicity of the drugs was evaluated. The findings showed that the combination of ketotifen with indomethacin (SJP-002C) or naproxen both reduce viral yield. Compared to ketotifen alone (60% inhibition at EC50), an increase in percentage inhibition of SARS-CoV-2 to 79%, 83% and 93% was found when co-administered with 25, 50 and 100 μM indomethacin, respectively. Compared to ketotifen alone, an increase in percentage inhibition of SARS-CoV-2 to 68%, 68% and 92% was found when co-administered with 25, 50 and 100 μM naproxen, respectively. For both drug combinations the observations suggest an additive or synergistic effect, compared to administering the drugs alone. No cytotoxic effects were observed for the administered dosages of ketotifen, naproxen, and indomethacin. Further research is warranted to investigate the efficacy of the combination of ketotifen with indomethacin (SJP-002C) or naproxen in the treatment of SARS-CoV-2 infection in humans. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
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11 pages, 1091 KiB  
Article
Treatment Protocol for COVID-19 Based on T2R Phenotype
by Mohamed A. Taha, Christian A. Hall, Colin J. Shortess, Richard F. Rathbone and Henry P. Barham
Viruses 2021, 13(3), 503; https://0-doi-org.brum.beds.ac.uk/10.3390/v13030503 - 18 Mar 2021
Cited by 6 | Viewed by 5841
Abstract
COVID-19 has become a global pandemic of the highest priority. Multiple treatment protocols have been proposed worldwide with no definitive answer for acure. A prior retrospective study showed association between bitter taste receptor 38 (T2R38) phenotypes and the severity of COVID-19. Based on [...] Read more.
COVID-19 has become a global pandemic of the highest priority. Multiple treatment protocols have been proposed worldwide with no definitive answer for acure. A prior retrospective study showed association between bitter taste receptor 38 (T2R38) phenotypes and the severity of COVID-19. Based on this, we proposed assessing the different T2R38 phenotypes response towards a targeted treatment protocol. Starting July 2020 till December 2020, we tested subjects for T2R38 phenotypic expression (supertasters, tasters, and nontasters). Subjects who were subsequently infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (diagnosed via PCR) were included. Based on their taster status, supertasters were given dexamethasone for 4 days; tasters were given azithromycin and dexamethasone +/− hydroxychloroquine for 7 days; and nontasters were given azithromycin and dexamethasone for 12 days. Subjects were followed prospectively and their outcomes were documented. Seven hundred forty-seven COVID-19 patients were included, with 184 (24.7%) supertasters, 371 (49.6%) tasters, and192 (25.7%) nontasters. The average duration of symptoms with the treatment protocol was 5 days for supertasters, 8.1 days for tasters, and 16.2 days for nontasters. Only three subjects (0.4%) required hospitalization (3/3 nontasters). Targeted treatment protocol showed significant correlation (p < 0.05) based on patients’ T2R38 phenotypic expression. Assessing treatment protocols for COVID-19 patients according to their T2R38 phenotype could provide insight into the inconsistent results obtained from the different studies worldwide. Further study is warranted on the categorization of patients based on their T2R38 phenotype. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
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11 pages, 935 KiB  
Article
The Combination of Bromelain and Acetylcysteine (BromAc) Synergistically Inactivates SARS-CoV-2
by Javed Akhter, Grégory Quéromès, Krishna Pillai, Vahan Kepenekian, Samina Badar, Ahmed H. Mekkawy, Emilie Frobert, Sarah J. Valle and David L. Morris
Viruses 2021, 13(3), 425; https://0-doi-org.brum.beds.ac.uk/10.3390/v13030425 - 06 Mar 2021
Cited by 24 | Viewed by 45449
Abstract
Severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is the cause of a worldwide pandemic, currently with limited therapeutic options. The spike glycoprotein and envelope protein of SARS-CoV-2, containing disulfide bridges for stabilization, represent an attractive target as they are essential for binding to [...] Read more.
Severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is the cause of a worldwide pandemic, currently with limited therapeutic options. The spike glycoprotein and envelope protein of SARS-CoV-2, containing disulfide bridges for stabilization, represent an attractive target as they are essential for binding to the ACE2 receptor in host cells present in the nasal mucosa. Bromelain and Acetylcysteine (BromAc) has synergistic action against glycoproteins by breakage of glycosidic linkages and disulfide bonds. We sought to determine the effect of BromAc on the spike and envelope proteins and its potential to reduce infectivity in host cells. Recombinant spike and envelope SARS-CoV-2 proteins were disrupted by BromAc. Spike and envelope protein disulfide bonds were reduced by Acetylcysteine. In in vitro whole virus culture of both wild-type and spike mutants, SARS-CoV-2 demonstrated a concentration-dependent inactivation from BromAc treatment but not from single agents. Clinical testing through nasal administration in patients with early SARS-CoV-2 infection is imminent. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
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10 pages, 975 KiB  
Article
Recent Hydroxychloroquine Use Is Not Significantly Associated with Positive PCR Results for SARS-CoV-2: A Nationwide Observational Study in South Korea
by Seongman Bae, Byeongzu Ghang, Ye-Jee Kim, Joon Seo Lim, Sung-Cheol Yun, Yong-Gil Kim, Sang-Oh Lee and Sung-Han Kim
Viruses 2021, 13(2), 329; https://0-doi-org.brum.beds.ac.uk/10.3390/v13020329 - 20 Feb 2021
Cited by 4 | Viewed by 3285
Abstract
Background: To evaluate the role of hydroxychloroquine (HCQ) as pre-exposure prophylaxis against coronavirus disease 2019 (COVID-19), we investigated the prevalence of positive test results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing according to recent HCQ use in patients who had been [...] Read more.
Background: To evaluate the role of hydroxychloroquine (HCQ) as pre-exposure prophylaxis against coronavirus disease 2019 (COVID-19), we investigated the prevalence of positive test results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing according to recent HCQ use in patients who had been tested using nationwide health-insurance data of South Korea. Methods: All adults tested for SARS-CoV-2 from 20 January 2020 to 15 May 2020 were identified. HCQ users were defined as patients who had been pretreated with HCQ for at least 30 days until the date of SARS-CoV-2 testing. The prevalence of positive PCR results for SARS-CoV-2 was compared between HCQ users and nonusers. Results: Of a total of 216,686 individuals who had been tested for SARS-CoV-2, 743 (0.3%) were pretreated with HCQ. The prevalence of positive results was not significantly different between HCQ users (2.2%) and nonusers (2.7%; P = 0.35), with an odds ratio of 0.79 (95% confidence interval (CI), 0.48–1.30). Propensity score-matched-cohort analysis showed similar results in terms of the prevalence of positive results (2.2% in HCQ users vs. 3.1% in nonusers; P = 0.18), with an odds ratio of 0.69 (95% CI, 0.40–1.19). The rate of positive PCR was not significantly different in long-term HCQ users (more than 3 or 6 months) compared with nonusers. Conclusions: In this population-based study, recent exposure to HCQ was not significantly associated with a lower risk of SARS-CoV-2 infection. Our data do not support the use of HCQ as pre-exposure prophylaxis against COVID-19. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
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23 pages, 4443 KiB  
Article
Structure-Based Identification of Natural Products as SARS-CoV-2 Mpro Antagonist from Echinacea angustifolia Using Computational Approaches
by Shiv Bharadwaj, Sherif Aly El-Kafrawy, Thamir A. Alandijany, Leena Hussein Bajrai, Altaf Ahmad Shah, Amit Dubey, Amaresh Kumar Sahoo, Umesh Yadava, Mohammad Amjad Kamal, Esam Ibraheem Azhar, Sang Gu Kang and Vivek Dhar Dwivedi
Viruses 2021, 13(2), 305; https://0-doi-org.brum.beds.ac.uk/10.3390/v13020305 - 15 Feb 2021
Cited by 25 | Viewed by 4554
Abstract
Coronavirus disease-19 (COVID-19) pandemic, caused by the novel SARS-CoV-2 virus, continues to be a global threat. The number of cases and deaths will remain escalating due to the lack of effective therapeutic agents. Several studies have established the importance of the viral main [...] Read more.
Coronavirus disease-19 (COVID-19) pandemic, caused by the novel SARS-CoV-2 virus, continues to be a global threat. The number of cases and deaths will remain escalating due to the lack of effective therapeutic agents. Several studies have established the importance of the viral main protease (Mpro) in the replication of SARS-CoV-2 which makes it an attractive target for antiviral drug development, including pharmaceutical repurposing and other medicinal chemistry approaches. Identification of natural products with considerable inhibitory potential against SARS-CoV-2 could be beneficial as a rapid and potent alternative with drug-likeness by comparison to de novo antiviral drug discovery approaches. Thereof, we carried out the structure-based screening of natural products from Echinacea-angustifolia, commonly used to prevent cold and other microbial respiratory infections, targeting SARS-CoV-2 Mpro. Four natural products namely, Echinacoside, Quercetagetin 7-glucoside, Levan N, Inulin from chicory, and 1,3-Dicaffeoylquinic acid, revealed significant docking energy (>−10 kcal/mol) in the SARS-CoV-2 Mpro catalytic pocket via substantial intermolecular contacts formation against co-crystallized ligand (<−4 kcal/mol). Furthermore, the docked poses of SARS-CoV-2 Mpro with selected natural products showed conformational stability through molecular dynamics. Exploring the end-point net binding energy exhibited substantial contribution of Coulomb and van der Waals interactions to the stability of respective docked conformations. These results advocated the natural products from Echinacea angustifolia for further experimental studies with an elevated probability to discover the potent SARS-CoV-2 Mpro antagonist with higher affinity and drug-likeness. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
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Review

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18 pages, 807 KiB  
Review
An Appraisal of the Current Scenario in Vaccine Research for COVID-19
by Wai Chin Chong, Dinesh K. Chellappan, Shakti D. Shukla, Gregory M. Peterson, Rahul P. Patel, Niraj Kumar Jha, Rajaraman D. Eri, Kamal Dua, Murtaza M. Tambuwala and Madhur D. Shastri
Viruses 2021, 13(7), 1397; https://0-doi-org.brum.beds.ac.uk/10.3390/v13071397 - 18 Jul 2021
Cited by 5 | Viewed by 4089
Abstract
The recent coronavirus disease 2019 (COVID-19) outbreak has drawn global attention, affecting millions, disrupting economies and healthcare modalities. With its high infection rate, COVID-19 has caused a colossal health crisis worldwide. While information on the comprehensive nature of this infectious agent, SARS-CoV-2, still [...] Read more.
The recent coronavirus disease 2019 (COVID-19) outbreak has drawn global attention, affecting millions, disrupting economies and healthcare modalities. With its high infection rate, COVID-19 has caused a colossal health crisis worldwide. While information on the comprehensive nature of this infectious agent, SARS-CoV-2, still remains obscure, ongoing genomic studies have been successful in identifying its genomic sequence and the presenting antigen. These may serve as promising, potential therapeutic targets in the effective management of COVID-19. In an attempt to establish herd immunity, massive efforts have been directed and driven toward developing vaccines against the SARS-CoV-2 pathogen. This review, in this direction, is aimed at providing the current scenario and future perspectives in the development of vaccines against SARS-CoV-2. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
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19 pages, 358 KiB  
Review
Potential Prophylactic Treatments for COVID-19
by Noam Ben-Zuk, Ido-David Dechtman, Itai Henn, Libby Weiss, Amichay Afriat, Esther Krasner and Yoav Gal
Viruses 2021, 13(7), 1292; https://0-doi-org.brum.beds.ac.uk/10.3390/v13071292 - 02 Jul 2021
Cited by 13 | Viewed by 5673
Abstract
The World Health Organization declared the SARS-CoV-2 outbreak a Public Health Emergency of International Concern at the end of January 2020 and a pandemic two months later. The virus primarily spreads between humans via respiratory droplets, and is the causative agent of Coronavirus [...] Read more.
The World Health Organization declared the SARS-CoV-2 outbreak a Public Health Emergency of International Concern at the end of January 2020 and a pandemic two months later. The virus primarily spreads between humans via respiratory droplets, and is the causative agent of Coronavirus Disease 2019 (COVID-19), which can vary in severity, from asymptomatic or mild disease (the vast majority of the cases) to respiratory failure, multi-organ failure, and death. Recently, several vaccines were approved for emergency use against SARS-CoV-2. However, their worldwide availability is acutely limited, and therefore, SARS-CoV-2 is still expected to cause significant morbidity and mortality in the upcoming year. Hence, additional countermeasures are needed, particularly pharmaceutical drugs that are widely accessible, safe, scalable, and affordable. In this comprehensive review, we target the prophylactic arena, focusing on small-molecule candidates. In order to consolidate a potential list of such medications, which were categorized as either antivirals, repurposed drugs, or miscellaneous, a thorough screening for relevant clinical trials was conducted. A brief molecular and/or clinical background is provided for each potential drug, rationalizing its prophylactic use as an antiviral or inflammatory modulator. Drug safety profiles are discussed, and current medical indications and research status regarding their relevance to COVID-19 are shortly reviewed. In the near future, a significant body of information regarding the effectiveness of drugs being clinically studied for COVID-19 is expected to accumulate, in addition to information regarding the efficacy of prophylactic treatments. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
24 pages, 1701 KiB  
Review
Long-COVID and Post-COVID Health Complications: An Up-to-Date Review on Clinical Conditions and Their Possible Molecular Mechanisms
by Bruno Silva Andrade, Sérgio Siqueira, Wagner Rodrigues de Assis Soares, Fernanda de Souza Rangel, Naiane Oliveira Santos, Andria dos Santos Freitas, Priscila Ribeiro da Silveira, Sandeep Tiwari, Khalid J Alzahrani, Aristóteles Góes-Neto, Vasco Azevedo, Preetam Ghosh and Debmalya Barh
Viruses 2021, 13(4), 700; https://0-doi-org.brum.beds.ac.uk/10.3390/v13040700 - 18 Apr 2021
Cited by 219 | Viewed by 30566
Abstract
The COVID-19 pandemic has infected millions worldwide, leaving a global burden for long-term care of COVID-19 survivors. It is thus imperative to study post-COVID (i.e., short-term) and long-COVID (i.e., long-term) effects, specifically as local and systemic pathophysiological outcomes of other coronavirus-related diseases (such [...] Read more.
The COVID-19 pandemic has infected millions worldwide, leaving a global burden for long-term care of COVID-19 survivors. It is thus imperative to study post-COVID (i.e., short-term) and long-COVID (i.e., long-term) effects, specifically as local and systemic pathophysiological outcomes of other coronavirus-related diseases (such as Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS)) were well-cataloged. We conducted a comprehensive review of adverse post-COVID health outcomes and potential long-COVID effects. We observed that such adverse outcomes were not localized. Rather, they affected different human systems, including: (i) immune system (e.g., Guillain–Barré syndrome, rheumatoid arthritis, pediatric inflammatory multisystem syndromes such as Kawasaki disease), (ii) hematological system (vascular hemostasis, blood coagulation), (iii) pulmonary system (respiratory failure, pulmonary thromboembolism, pulmonary embolism, pneumonia, pulmonary vascular damage, pulmonary fibrosis), (iv) cardiovascular system (myocardial hypertrophy, coronary artery atherosclerosis, focal myocardial fibrosis, acute myocardial infarction, cardiac hypertrophy), (v) gastrointestinal, hepatic, and renal systems (diarrhea, nausea/vomiting, abdominal pain, anorexia, acid reflux, gastrointestinal hemorrhage, lack of appetite/constipation), (vi) skeletomuscular system (immune-mediated skin diseases, psoriasis, lupus), (vii) nervous system (loss of taste/smell/hearing, headaches, spasms, convulsions, confusion, visual impairment, nerve pain, dizziness, impaired consciousness, nausea/vomiting, hemiplegia, ataxia, stroke, cerebral hemorrhage), (viii) mental health (stress, depression and anxiety). We additionally hypothesized mechanisms of action by investigating possible molecular mechanisms associated with these disease outcomes/symptoms. Overall, the COVID-19 pathology is still characterized by cytokine storm that results to endothelial inflammation, microvascular thrombosis, and multiple organ failures. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
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19 pages, 1510 KiB  
Review
Target Product Profile Analysis of COVID-19 Vaccines in Phase III Clinical Trials and Beyond: An Early 2021 Perspective
by Colin D. Funk, Craig Laferrière and Ali Ardakani
Viruses 2021, 13(3), 418; https://0-doi-org.brum.beds.ac.uk/10.3390/v13030418 - 05 Mar 2021
Cited by 44 | Viewed by 15059
Abstract
The coronavirus SARS-CoV-2, which causes Coronavirus disease 2019 (COVID-19), has infected more than 100 million people globally and caused over 2.5 million deaths in just over one year since its discovery in Wuhan, China in December 2019. The pandemic has evoked widespread collateral [...] Read more.
The coronavirus SARS-CoV-2, which causes Coronavirus disease 2019 (COVID-19), has infected more than 100 million people globally and caused over 2.5 million deaths in just over one year since its discovery in Wuhan, China in December 2019. The pandemic has evoked widespread collateral damage to societies and economies, and has destabilized mental health and well-being. Early in 2020, unprecedented efforts went into the development of vaccines that generate effective antibodies to the SARS-CoV-2 virus. Teams developing twelve candidate vaccines, based on four platforms (messenger RNA, non-replicating viral vector, protein/virus-like particle, and inactivated virus) had initiated or announced the Phase III clinical trial stage by early November 2020, with several having received emergency use authorization in less than a year. Vaccine rollout has proceeded around the globe. Previously, we and others had proposed a target product profile (TPP) for ideal/optimal and acceptable/minimal COVID-19 vaccines. How well do these candidate vaccines stack up to a harmonized TPP? Here, we perform a comparative analysis in several categories of these candidate vaccines based on the latest available trial data and highlight the early successes as well as the hurdles and barriers yet to be overcome for ending the global COVID-19 pandemic. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
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14 pages, 948 KiB  
Review
Pharmacogenetics Approach for the Improvement of COVID-19 Treatment
by Ingrid Fricke-Galindo and Ramcés Falfán-Valencia
Viruses 2021, 13(3), 413; https://0-doi-org.brum.beds.ac.uk/10.3390/v13030413 - 05 Mar 2021
Cited by 20 | Viewed by 8203
Abstract
The treatment of coronavirus disease 2019 (COVID-19) has been a challenge. The efficacy of several drugs has been evaluated and variability in drug response has been observed. Pharmacogenetics could explain this variation and improve patients’ outcomes with this complex disease; nevertheless, several disease-related [...] Read more.
The treatment of coronavirus disease 2019 (COVID-19) has been a challenge. The efficacy of several drugs has been evaluated and variability in drug response has been observed. Pharmacogenetics could explain this variation and improve patients’ outcomes with this complex disease; nevertheless, several disease-related issues must be carefully reviewed in the pharmacogenetic study of COVID-19 treatment. We aimed to describe the pharmacogenetic variants reported for drugs used for COVID-19 treatment (remdesivir, oseltamivir, lopinavir, ritonavir, azithromycin, chloroquine, hydroxychloroquine, ivermectin, and dexamethasone). In addition, other factors relevant to the design of pharmacogenetic studies were mentioned. Variants in CYP3A4, CYP3A5, CYP2C8, CY2D6, ABCB1, ABCC2, and SLCO1B1, among other variants, could be included in pharmacogenetic studies of COVID-19 treatment. Besides, nongenetic factors such as drug–drug interactions and inflammation should be considered in the search for personalized therapy of COVID-19. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
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16 pages, 3299 KiB  
Review
Domains and Functions of Spike Protein in SARS-Cov-2 in the Context of Vaccine Design
by Xuhua Xia
Viruses 2021, 13(1), 109; https://0-doi-org.brum.beds.ac.uk/10.3390/v13010109 - 14 Jan 2021
Cited by 189 | Viewed by 21422
Abstract
The spike protein in SARS-CoV-2 (SARS-2-S) interacts with the human ACE2 receptor to gain entry into a cell to initiate infection. Both Pfizer/BioNTech’s BNT162b2 and Moderna’s mRNA-1273 vaccine candidates are based on stabilized mRNA encoding prefusion SARS-2-S that can be produced after the [...] Read more.
The spike protein in SARS-CoV-2 (SARS-2-S) interacts with the human ACE2 receptor to gain entry into a cell to initiate infection. Both Pfizer/BioNTech’s BNT162b2 and Moderna’s mRNA-1273 vaccine candidates are based on stabilized mRNA encoding prefusion SARS-2-S that can be produced after the mRNA is delivered into the human cell and translated. SARS-2-S is cleaved into S1 and S2 subunits, with S1 serving the function of receptor-binding and S2 serving the function of membrane fusion. Here, I dissect in detail the various domains of SARS-2-S and their functions discovered through a variety of different experimental and theoretical approaches to build a foundation for a comprehensive mechanistic understanding of how SARS-2-S works to achieve its function of mediating cell entry and subsequent cell-to-cell transmission. The integration of structure and function of SARS-2-S in this review should enhance our understanding of the dynamic processes involving receptor binding, multiple cleavage events, membrane fusion, viral entry, as well as the emergence of new viral variants. I highlighted the relevance of structural domains and dynamics to vaccine development, and discussed reasons for the spike protein to be frequently featured in the conspiracy theory claiming that SARS-CoV-2 is artificially created. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
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18 pages, 779 KiB  
Review
Lead SARS-CoV-2 Candidate Vaccines: Expectations from Phase III Trials and Recommendations Post-Vaccine Approval
by Ebenezer Tumban
Viruses 2021, 13(1), 54; https://0-doi-org.brum.beds.ac.uk/10.3390/v13010054 - 31 Dec 2020
Cited by 54 | Viewed by 11462
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted primarily through respiratory droplets/aerosols and it causes COVID-19. The virus infects epithelial cells by using the spike protein on its surface to bind to angiotensin-converting enzyme 2 receptor on the cells. Thus, candidate vaccines [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted primarily through respiratory droplets/aerosols and it causes COVID-19. The virus infects epithelial cells by using the spike protein on its surface to bind to angiotensin-converting enzyme 2 receptor on the cells. Thus, candidate vaccines targeting the spike protein are currently being developed to prevent against infections. Approximately 44 SARS-CoV-2 candidate vaccines are in clinical trials (phase I–III) and an additional 164 candidates are in preclinical stages. The efficacy data from phase I/II trials of lead candidate vaccines look very promising with virus-neutralizing geometric mean antibody titers in the range of 16.6–3906. Most recently, two SARS-CoV-2 candidate vaccines, BNT162b2 and mRNA-1273, have been granted the first emergency use authorization (EUA) in the U.S.; BNT162b2 has also been granted an EUA in the United Kingdom, Canada, and in the European Union. This review assesses whether SARS-CoV-2 candidate vaccines (with approved EUA or in phase III trials) meet the criteria for an ideal SARS-CoV-2 vaccine. The review concludes with expectations from phase III trials and recommendations for phase IV studies (post-vaccine approval). Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
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Other

3 pages, 181 KiB  
Comment
Prominent Efficacy of Amantadine against Human Borna Disease Virus Infection In Vitro and In Vivo. Comment on Fink et al. Amantadine Inhibits SARS-CoV-2 In Vitro. Viruses 2021, 13, 539
by Liv Bode, Detlef E. Dietrich, Carsten W. Spannhuth and Hanns Ludwig
Viruses 2022, 14(3), 494; https://0-doi-org.brum.beds.ac.uk/10.3390/v14030494 - 28 Feb 2022
Cited by 3 | Viewed by 1962
Abstract
Amantadine (1-amino-adamantane) is a versatile antiviral compound which has been licensed for decades against influenza viruses. During the Corona pandemic, its effect to inhibit SARS-CoV-2 in vitro has been investigated. However, an in vivo oral inapplicability was concluded due to ID50 doses [...] Read more.
Amantadine (1-amino-adamantane) is a versatile antiviral compound which has been licensed for decades against influenza viruses. During the Corona pandemic, its effect to inhibit SARS-CoV-2 in vitro has been investigated. However, an in vivo oral inapplicability was concluded due to ID50 doses exceeding eight times the estimated maximum tolerable plasma levels reached by 600 mg orally daily. In contrast, amantadine has been shown to be extraordinarily efficient against human neurotropic Borna disease virus (BoDV-1), presenting with both anti-depressive and anti-viral efficacy against a placebo, achieved by a well-tolerated low oral daily dose of 200 mg amantadine. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
1 pages, 157 KiB  
Retraction
Retraction: Samaha et al. Effects of a Single Dose of Ivermectin on Viral and Clinical Outcomes in Asymptomatic SARS-CoV-2 Infected Subjects: A Pilot Clinical Trial in Lebanon. Viruses 2021, 13, 989
by Ali A. Samaha, Hussein Mouawia, Mirna Fawaz, Hamad Hassan, Ali Salami, Ali Al Bazzal, Hamid Bou Saab, Mohamed Al-Wakeel, Ahmad Alsaabi, Mohamad Chouman, Mahmoud Al Moussawi, Hassan Ayoub, Ali Raad, Ola Hajjeh, Ali H. Eid and Houssam Raad
Viruses 2021, 13(11), 2154; https://0-doi-org.brum.beds.ac.uk/10.3390/v13112154 - 26 Oct 2021
Cited by 13 | Viewed by 14388
Abstract
The journal retracts the article, Effects of a Single Dose of Ivermectin on Viral and Clinical Outcomes in Asymptomatic SARS-CoV-2 Infected Subjects: A Pilot Clinical Trial in Lebanon [...] Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
9 pages, 399 KiB  
Brief Report
Effect of Aprotinin and Avifavir® Combination Therapy for Moderate COVID-19 Patients
by Andrey A. Ivashchenko, Valeria N. Azarova, Alina N. Egorova, Ruben N. Karapetian, Dmitry V. Kravchenko, Natalia V. Krivonos, Vladimir G. Loginov, Stanislav V. Poyarkov, Elena A. Merkulova, Olga S. Rosinkova, Nikolay P. Savchuk, Mikhail A. Topr, Elena N. Simakina, Elena V. Yakubova and Alexandre V. Ivachtchenko
Viruses 2021, 13(7), 1253; https://0-doi-org.brum.beds.ac.uk/10.3390/v13071253 - 27 Jun 2021
Cited by 10 | Viewed by 2884
Abstract
COVID-19 is a contagious multisystem inflammatory disease caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We studied the efficacy of Aprotinin (nonspecific serine proteases inhibitor) in combination with Avifavir® or Hydroxychloroquine (HCQ) drugs, which are recommended by the Russian Ministry [...] Read more.
COVID-19 is a contagious multisystem inflammatory disease caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We studied the efficacy of Aprotinin (nonspecific serine proteases inhibitor) in combination with Avifavir® or Hydroxychloroquine (HCQ) drugs, which are recommended by the Russian Ministry of Health for the treatment therapy of moderate COVID-19 patients. This prospective single-center study included participants with moderate COVID-19-related pneumonia, laboratory-confirmed SARS-CoV-2, and admitted to the hospitals. Patients received combinations of intravenous (IV) Aprotinin (1,000,000 KIU daily, 3 days) and HCQ (cohort 1), inhalation (inh) treatment with Aprotinin (625 KIU four times per day, 5 days) and HCQ (cohort 2) or IV Aprotinin (1,000,000 KIU daily for 5 days) and Avifavir (cohort 3). In cohorts 1–3, the combination therapy showed 100% efficacy in preventing the transfer of patients (n = 30) to the intensive care unit (ICU). The effect of the combination therapy in cohort 3 was the most prominent, and the median time to SARS-CoV-2 elimination was 3.5 days (IQR 3.0–4.0), normalization of the CRP concentration was 3.5 days (IQR 3–5), of the D-dimer concentration was 5 days (IQR 4 to 5); body temperature was 1 day (IQR 1–3), improvement in clinical status or discharge from the hospital was 5 days (IQR 5–5), and improvement in lung lesions of patients on 14 day was 100%. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
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10 pages, 1043 KiB  
Brief Report
Amantadine Inhibits SARS-CoV-2 In Vitro
by Klaus Fink, Andreas Nitsche, Markus Neumann, Marica Grossegesse, Karl-Heinz Eisele and Wojciech Danysz
Viruses 2021, 13(4), 539; https://0-doi-org.brum.beds.ac.uk/10.3390/v13040539 - 24 Mar 2021
Cited by 41 | Viewed by 18442
Abstract
Since the SARS-CoV-2 pandemic started in late 2019, the search for protective vaccines and for drug treatments has become mandatory to fight the global health emergency. Travel restrictions, social distancing, and face masks are suitable counter measures, but may not bring the pandemic [...] Read more.
Since the SARS-CoV-2 pandemic started in late 2019, the search for protective vaccines and for drug treatments has become mandatory to fight the global health emergency. Travel restrictions, social distancing, and face masks are suitable counter measures, but may not bring the pandemic under control because people will inadvertently or at a certain degree of restriction severity or duration become incompliant with the regulations. Even if vaccines are approved, the need for antiviral agents against SARS-CoV-2 will persist. However, unequivocal evidence for efficacy against SARS-CoV-2 has not been demonstrated for any of the repurposed antiviral drugs so far. Amantadine was approved as an antiviral drug against influenza A, and antiviral activity against SARS-CoV-2 has been reasoned by analogy but without data. We tested the efficacy of amantadine in vitro in Vero E6 cells infected with SARS-CoV-2. Indeed, amantadine inhibited SARS-CoV-2 replication in two separate experiments with IC50 concentrations between 83 and 119 µM. Although these IC50 concentrations are above therapeutic amantadine levels after systemic administration, topical administration by inhalation or intranasal instillation may result in sufficient amantadine concentration in the airway epithelium without high systemic exposure. However, further studies in other models are needed to prove this hypothesis. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
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