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Emerging Viruses and Antiviral Drugs

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A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Virology".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 22228

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Special Issue Editors

Dr. Veronica Soloveva

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Guest Editor

Department of Quantitative Biosciences, Merck, Boston, MA, USA
Interests: antiviral drug discovery; phenotypic drug discovery; HCI
Special Issues, Collections and Topics in MDPI journals

Dr. Miguel A. Martín-Acebes

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Guest Editor

Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), 28040 Madrid, Spain
Interests: virus; arbovirus; flavivirus; dengue; West Nile; Zika; zoonoses; lipid; virus–host interaction; sphingolipids; fatty acids; metabolism; antivirals; vaccines
Special Issues, Collections and Topics in MDPI journals

Dr. Sina Bavari

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Guest Editor

CSO, Co-Founder of Healion Bio, Frederick, MD, USA
Interests: virology; oncology; drug discovery; drug development

Special Issue Information

Dear Colleagues,

Emerging viruses are a very broad category that includes not only newly discovered viruses but also re-emerging variants of known viruses. These viruses continue to cause mass disruption by creating constant threat to public health. In the last 20 years, we have observed a variety of viral outbreaks, such as severe acute respiratory symptom (SARS), H1N1 influenza, Ebola virus, Middle East respiratory syndrome coronavirus (MERS-CoV), Rift Valley fever, Crimean Congo hemorrhagic fever, Nipah and Hendra viruses, severe fever with thrombocytopenia syndrome virus (SFTSV), yellow fever virus (YFV), Zika virus, and the ongoing SARS-CoV-2. The globalization of the economies and quick-paced traveling patterns of human populations, combined with climate change, are creating ample opportunities for mass spread of viral infections. The multiple surges of SARS-CoV-2 variants have quickly exposed the challenges and limitations of vaccines and various antiviral treatments. For example, SARS-CoV-2 virus transmission has proven difficult to manage with current vaccines and therapeutic approaches. There is a strong need to position immune modulating modalities and other novel antivirals to suppress viral transmission and infection by inhibiting cellular pathways essential for viral infection. The development of broad-spectrum antiviral drugs can provide an additional level of defense while specific antivirals are being developed. This approach has shown some indication of success against SARS-CoV-2 and may be appropriate to be implemented for future emerging viruses. This Special Issue, “Emerging Viruses and Antiviral Drugs”, focuses on various antiviral approaches to manage emerging and re-emerging viruses and will include antiviral drug discovery, discovery of the mechanism of actions, new targets, and upcoming and established technologies used for discovery and development of antiviral drugs.

Dr. Veronica Soloveva
Dr. Miguel A. Martín-Acebes
Dr. Sina Bavari
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.

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 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

emerging viruses
antiviral therapies
antiviral drugs
drug discovery and development
mechanism of action

Published Papers (10 papers)

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Research

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16 pages, 2609 KiB

Open AccessArticle

Humoral Immunity of Unvaccinated COVID-19 Recovered vs. Naïve BNT162b2 Vaccinated Individuals: A Prospective Longitudinal Study

by Gili Joseph, Carmit Cohen, Carmit Rubin, Havi Murad, Victoria Indenbaum, Keren Asraf, Yael Weiss-Ottolenghi, Gabriella Segal-Lieberman, Yitshak Kreiss, Yaniv Lustig and Gili Regev-Yochay

Microorganisms 2023, 11(7), 1628; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms11071628 - 22 Jun 2023

Cited by 1 | Viewed by 1017

Abstract

To study the differences in the immune response to SARS-CoV-2 infection compared to the response to vaccination, we characterized the humoral immune kinetics of these situations. In this prospective longitudinal study, we followed unvaccinated COVID-19-recovered individuals (n = 130) and naïve, two-dose BNT162b2-vaccinated individuals (n = 372) who were age- and BMI-matched for six months during the first pandemic year. Anti-RBD-IgG, neutralizing antibodies (NAbs), and avidity were assessed monthly. For recovered patients, data on symptoms and the severity of the disease were collected. Anti-RBD-IgG and NAbs titers at peak were higher after vaccination vs. after infection, but the decline was steeper (peak log IgG: 3.08 vs. 1.81, peak log NAbs: 5.93 vs. 5.04, slopes: −0.54 vs. −0.26). Peak anti-RBD-IgG and NAbs were higher in recovered individuals with BMI > 30 and in older individuals compared to individuals with BMI < 30, younger population. Of the recovered, 42 (36%) experienced long-COVID symptoms. Avidity was initially higher in vaccinated individuals compared with recovered individuals, though with time, it increased in recovered individuals but not among vaccinated individuals. Here, we show that while the initial antibody titers, neutralization, and avidity are lower in SARS-CoV-2-recovered individuals, they persist for a longer duration. These results suggest differential protection against COVID-19 in recovered-unvaccinated vs. naïve-vaccinated individuals. Full article

(This article belongs to the Special Issue Emerging Viruses and Antiviral Drugs)

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11 pages, 1548 KiB

Open AccessArticle

Viral Fitness of Baloxavir-Resistant Recombinant Influenza B/Victoria- and B/Yamagata-like Viruses Harboring the I38T PA Change, In Vitro, Ex Vivo and in Guinea Pigs

by Amel Saim-Mamoun, Julie Carbonneau, Chantal Rhéaume, Yacine Abed and Guy Boivin

Microorganisms 2023, 11(5), 1095; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms11051095 - 22 Apr 2023

Viewed by 1317

Abstract

Seasonal influenza A and B viruses may cause severe infections requiring therapeutic interventions. Baloxavir, the latest antiviral drug approved against those infections, targets the endonuclease activity encoded by the polymerase acidic (PA) protein. While appearing effective at cessation of viral shedding, baloxavir demonstrated a low barrier of resistance. Herein, we aimed to assess the impact of PA-I38T substitution, a major marker of baloxavir-resistance, on the fitness of contemporary influenza B viruses. Recombinant wild-type (WT) influenza B/Phuket/2073/13 (B/Yamagata/16/88-like) and B/Washington/02/19 (B/Victoria/2/87-like) viruses and their respective PA-I38T mutants were used to evaluate replication kinetics in vitro, using A549 and Calu3 cells, and ex vivo, using nasal human airway epithelium (HAE) cells. Infectivity was also assessed in guinea pigs. In the B/Washington/02/19 background, there were no major differences between the recombinant WT virus and its I38T mutant when viral replication kinetics were evaluated in human lung cell lines and HAE as well as in nasal washes of experimentally infected guinea pigs. By contrast, the I38T mutation moderately impacted the B/Phuket/2073/13 viral fitness. In conclusion, contemporary influenza B viruses that may acquire baloxavir-resistance through the PA-I38T substitution could retain a significant level of fitness, highlighting the importance of monitoring the emergence of such variant. Full article

(This article belongs to the Special Issue Emerging Viruses and Antiviral Drugs)

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17 pages, 2777 KiB

Open AccessArticle

Comparative Molecular and Epidemiological Analyses of Israeli Bluetongue Viruses Serotype 1 and 9 Causing Outbreaks in 2018–2020

by Natalia Golender, Eyal Klement, Anita Kovtunenko, Boris Even-Tov, Lior Zamir, Eitan Tiomkin, Gabriel Kenigswald and Bernd Hoffmann

Microorganisms 2023, 11(2), 366; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms11020366 - 01 Feb 2023

Cited by 1 | Viewed by 1301

Abstract

Israel is endemic to bluetongue virus (BTV). The introduction of novel-for-the-region arboviruses have been recorded annually in recent years. In 2019, previously non-reported in-the-country BTV-1 and BTV-9 were identified. BTV-1 caused a single-season outbreak, probably linked to mild infection in ruminants. BTV-9 was retrospectively detected in the field samples collected from August 2018 until 2020. It was the dominant serotype in 2019, out of the six serotypes recorded during that calendar year. Clinical manifestation of the disease in cases diagnosed with BTV-9 were compared to those in cases determined to have BTV-1. BLAST and phylogenetic analyses of BTV-1 showed that the nucleotide (nt) sequence coding the viral outer protein 1 (VP2) determining the serotype is closely related to BTV-1 isolated in Sudan in 1987, and the coding sequence of the outer protein 2 (VP5) is related to South African BTV-1 from 2017. A probable common ancestor with Libyan BTV-9 strains isolated in 2008 was seen in an analysis of Israeli BTV-9 nt sequences. Notably, the outbreak-caused BTV-9 strains collected in 2019 exhibited a distinct level of genetic reassortment with local Israeli strains compared to BTV-9 strains registered in 2018 and 2020. Full article

(This article belongs to the Special Issue Emerging Viruses and Antiviral Drugs)

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10 pages, 828 KiB

Open AccessArticle

The Use of Rapid COVID-19 Antigen Test in the Emergency Department as a Decision-Support Tool

by Lilac Meltzer, Sharon Amit, Mayan Gilboa, Ilana Tal, Bella Mechnik, Avi Irony, Hindi Engelrad, Avi Epstein, Yael Frenkel-Nir, Yuval Levy, Yitshak Kreiss and Gili Regev-Yochay

Microorganisms 2023, 11(2), 284; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms11020284 - 21 Jan 2023

Viewed by 1389

Abstract

The emergency department (ED) is the initial point of contact between hospital staff and patients potentially infected with SARS-CoV-2, thus, prevention of inadvertent exposure to other patients is a top priority. We aimed to assess whether the introduction of antigen-detecting rapid diagnostic tests (Ag-RDTs) to the ED affected the likelihood of unwanted SARS-CoV-2 exposures. In this retrospective single-center study, we compared the rate of unwarranted exposure of uninfected adult ED patients to SARS-CoV-2 during two separate research periods; one before Ag-RDTs were introduced, and one with Ag-RDT used as a decision-support tool. The introduction of Ag-RDTs to the ED significantly decreased the relative risk of SARS-CoV-2-negative patients being incorrectly assigned to the COVID-19 designated site (“red ED”), by 97%. There was no increase in the risk of SARS-CoV-2-positive patients incorrectly assigned to the COVID-19-free site (“green ED”). In addition, duration of ED admission was reduced in both the red and the green ED. Therefore, implementing the Ag-RDT-based triage protocol proved beneficial in preventing potential COVID-19 nosocomial transmission. Full article

(This article belongs to the Special Issue Emerging Viruses and Antiviral Drugs)

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14 pages, 3296 KiB

Open AccessEditor’s ChoiceArticle

In Vitro and In Silico Analysis of the Inhibitory Activity of EGCG-Stearate against Herpes Simplex Virus-2

by James D. Stamos, Lee H. Lee, Calvin Taylor, Tony Elias and Sandra D. Adams

Microorganisms 2022, 10(7), 1462; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10071462 - 20 Jul 2022

Cited by 4 | Viewed by 2430

Abstract

About half a billion people worldwide are infected with herpes simplex virus-2 (HSV-2). Prolonged treatment with acyclovir (ACV) and its analogs leads to the development of resistant strains. The aim of this study was to investigate the antiviral potential of epigallocatechin gallate (EGCG) from Camellia sinensis and a stable analog EGCG-stearate (EGCG-S) against HSV-2 in cultured Vero cells. Cell viability and cell proliferation assays were used to determine the non-cytotoxic concentrations on cultured Vero cells. HSV-2 with a green fluorescent protein (GFP) fusion protein of VP26 virions were treated with non-cytotoxic concentrations of EGCG and EGCG-S. The effects on infectivity and mechanisms were determined by plaque assay, attachment and penetration assays, confocal microscopy, qPCR, and in silico modeling analysis. Our results demonstrate that treatment of HSV-2 virions with EGCG and EGCG-S at a concentration of 75 µM showed greater than 99.9% inhibition by inhibiting the attachment of HSV-2 virions to host cells. The bioinformatic analysis indicated high binding affinity of EGCG-S for glycoprotein D; thus EGCG-S may block fusion of HSV-2 and the cell membrane, preventing entry of HSV-2 into the cell. Full article

(This article belongs to the Special Issue Emerging Viruses and Antiviral Drugs)

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19 pages, 2894 KiB

Open AccessArticle

Riboflavin, a Potent Neuroprotective Vitamin: Focus on Flavivirus and Alphavirus Proteases

by Raphael J. Eberle, Danilo S. Olivier, Marcos S. Amaral, Carolina C. Pacca, Mauricio L. Nogueira, Raghuvir K. Arni, Dieter Willbold and Monika A. Coronado

Microorganisms 2022, 10(7), 1331; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10071331 - 30 Jun 2022

Cited by 4 | Viewed by 2130

Abstract

Several neurotropic viruses are members of the flavivirus and alphavirus families. Infections caused by these viruses may cause long-term neurological sequelae in humans. The continuous emergence of infections caused by viruses around the world, such as the chikungunya virus (CHIKV) (Alphavirus genus), the zika virus (ZIKV) and the yellow fever virus (YFV) (both of the Flavivirus genus), warrants the development of new strategies to combat them. Our study demonstrates the inhibitory potential of the water-soluble vitamin riboflavin against NS2B/NS3^pro of ZIKV and YFV and nsP2^pro of CHIKV. Riboflavin presents a competitive inhibition mode with IC₅₀ values in the medium µM range of 79.4 ± 5.0 µM for ZIKV NS2B/NS3^pro and 45.7 ± 2.9 μM for YFV NS2B/NS3^pro. Against CHIKV nsP2^pro, the vitamin showed a very strong effect (93 ± 5.7 nM). The determined dissociation constants (K_D) are significantly below the threshold value of 30 µM. The ligand binding increases the thermal stability between 4 °C and 8 °C. Unexpectedly, riboflavin showed inhibiting activity against another viral protein; the molecule was also able to inhibit the viral entry of CHIKV. Molecular dynamics simulations indicated great stability of riboflavin in the protease active site, which validates the repurposing of riboflavin as a promising molecule in drug development against the viruses presented here. Full article

(This article belongs to the Special Issue Emerging Viruses and Antiviral Drugs)

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Review

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13 pages, 848 KiB

Open AccessReview

Efficacy and Safety of Two-Drug Regimens That Are Approved from 2018 to 2022 for the Treatment of Human Immunodeficiency Virus (HIV) Disease and Its Opportunistic Infections

by Palanisamy Sivanandy, Jess Ng Yujie, Kanini Chandirasekaran, Ooi Hong Seng and Nur Azrida Azhari Wasi

Microorganisms 2023, 11(6), 1451; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms11061451 - 31 May 2023

Cited by 2 | Viewed by 1618

Abstract

The human immunodeficiency virus (HIV) is a type of virus that targets the body’s immune cells. HIV infection can be divided into three phases: acute HIV infection, chronic HIV infection, and acquired immunodeficiency syndrome (AIDS). HIV-infected people are immunosuppressed and at risk of developing opportunistic infections such as pneumonia, tuberculosis, candidiasis, toxoplasmosis, and Salmonella infection. The two types of HIV are known as HIV-1 and HIV-2. HIV-1 is the predominant and more common cause of AIDS worldwide, with an estimated 38 million people living with HIV-1 while an estimated 1 to 2 million people live with HIV-2. No effective cures are currently available for HIV infection. Current treatments emphasise the drug’s safety and tolerability, as lifelong management is needed to manage HIV infection. The goal of this review is to study the efficacy and safety of newly approved drugs from 2018 to 2022 for the treatment of HIV by the United States Food and Drug Administration (US-FDA). The drugs included Cabotegravir and Rilpivirine, Fostemsavir, Doravirine, and Ibalizumab. From the review, switching to doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) was shown to be noninferior to the continuation of the previous regimen, efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) in virologically suppressed adults with HIV-1. However, DOR/3TC/TDF had shown a preferable safety profile with lower discontinuations due to adverse events (AEs), lower neuropsychiatric AEs, and a preferable lipid profile. Ibalizumab was also safe, well tolerated, and had been proven effective against multiple drug-resistant strains of viruses. Full article

(This article belongs to the Special Issue Emerging Viruses and Antiviral Drugs)

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19 pages, 1152 KiB

Open AccessReview

Influenza Treatment: Limitations of Antiviral Therapy and Advantages of Drug Combination Therapy

by Sania Batool, Santosh Chokkakula and Min-Suk Song

Microorganisms 2023, 11(1), 183; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms11010183 - 11 Jan 2023

Cited by 10 | Viewed by 4474

Abstract

Influenza infection is serious and debilitating for humans and animals. The influenza virus undergoes incessant mutation, segment recombination, and genome reassortment. As a result, new epidemics and pandemics are expected to emerge, making the elimination challenging of the disease. Antiviral therapy has been used for the treatment of influenza since the development of amantadine in the 1960s; however, its use is hampered by the emergence of novel strains and the development of drug resistance. Thus, combinational therapy with two or more antivirals or immunomodulators with different modes of action is the optimal strategy for the effective treatment of influenza infection. In this review, we describe current options for combination therapy, their performance, and constraints imposed by resistance, calling attention to the advantages of combination therapy against severe influenza infections. We also discuss the challenges of influenza therapy and the limitations of approved antiviral drugs. Full article

(This article belongs to the Special Issue Emerging Viruses and Antiviral Drugs)

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23 pages, 422 KiB

Open AccessReview

Viral Infection and Antiviral Treatments in Ocular Pathologies

by Francesco Petrillo, Arianna Petrillo, Francesca Paola Sasso, Antonietta Schettino, Angela Maione and Marilena Galdiero

Microorganisms 2022, 10(11), 2224; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10112224 - 10 Nov 2022

Cited by 3 | Viewed by 2678

Abstract

Ocular viral infections are common and widespread globally. These infectious diseases are a major cause of acute red eyes and vision loss. The eye and its nearby tissues can be infected by several viral agents, causing infections with a short course and limited ocular implications or a long clinical progression and serious consequences for the function and structure of the ocular region. Several surveillance studies underline the increased emergence of drug resistance among pathogenic viral strains, limiting treatment options for these infections. Currently, in the event of resistant infections, topical or systemic corticosteroids are useful in the management of associated immune reactions in the eye, which contribute to ocular dysfunction. Many cases of viral eye infections are misdiagnosed as being of bacterial origin. In these cases, therapy begins late and is not targeted at the actual cause of the infection, often leading to severe ocular compromises, such as corneal infiltrates, conjunctival scarring, and reduced visual acuity. The present study aims at a better understanding of the viral pathogens that cause eye infections, along with the treatment options available. Full article

(This article belongs to the Special Issue Emerging Viruses and Antiviral Drugs)

17 pages, 1279 KiB

Open AccessReview

A Novel Approach of Antiviral Drugs Targeting Viral Genomes

by Phuong Thi Hoang, Quynh Xuan Thi Luong, Ramadhani Qurrota Ayun, Yongjun Lee, Thuy Thi Bich Vo, Taehyun Kim and Sukchan Lee

Microorganisms 2022, 10(8), 1552; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10081552 - 31 Jul 2022

Cited by 1 | Viewed by 2771

Abstract

Outbreaks of viral diseases, which cause morbidity and mortality in animals and humans, are increasing annually worldwide. Vaccines, antiviral drugs, and antibody therapeutics are the most effective tools for combating viral infection. The ongoing coronavirus disease 2019 pandemic, in particular, raises an urgent need for the development of rapid and broad-spectrum therapeutics. Current antiviral drugs and antiviral antibodies, which are mostly specific at protein levels, have encountered difficulties because the rapid evolution of mutant viral strains resulted in drug resistance. Therefore, degrading viral genomes is considered a novel approach for developing antiviral drugs. The current article highlights all potent candidates that exhibit antiviral activity by digesting viral genomes such as RNases, RNA interference, interferon-stimulated genes 20, and CRISPR/Cas systems. Besides that, we introduce a potential single-chain variable fragment (scFv) that presents antiviral activity against various DNA and RNA viruses due to its unique nucleic acid hydrolyzing characteristic, promoting it as a promising candidate for broad-spectrum antiviral therapeutics. Full article

(This article belongs to the Special Issue Emerging Viruses and Antiviral Drugs)

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