Special Issue "Recent Advances in Antivirals for Emerging Viruses"

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Antimicrobial Agents and Resistance".

Deadline for manuscript submissions: closed (28 February 2021).

Special Issue Editors

Dr. Keivan Zandi
Website
Guest Editor
School of Medicine, Department of Pediatrics, Emory University, Atlanta, United States
Interests: antiviral research; arbovirology; molecular virology; natural products for drug discovery; infectious disease; molecular epidemiology; cancer research
Dr. James J. Kohler
Website
Guest Editor
School of Medicine, Department of Pediatrics, Emory University, Atlanta, United States

Special Issue Information

Dear Colleagues,

The emergence of Covid-19 is a reminder that new transmissible viruses have a potential global social, health, and economic impact. Current biological tools (including rapid and efficient cloning and sequencing) have advanced basic scientific efforts to identify viral enzymes of important novel and re-emerging human viruses (e.g., Dengue, West Nile, Zika, Chikungunya, Influenza, and now Coronaviruses). At the same time, drug discovery has exponentially expanded, resulting in vast libraries of compounds for screening direct antiviral activity. This Special issue will highlight recent advances in antiviral drug developments, including:

1) direct acting antivirals;

2) modifiers of immune activation;

3) inhibitors of specific cell activation pathways.

Dr. Keivan Zandi
Dr. James J. Kohler
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 papers will be 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. Microorganisms 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 2000 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

  • antiviral agents
  • broad-spectrum antivirals
  • antiviral response
  • emerging and re-emerging viral diseases
  • antiviral strategies
  • druggable antiviral targets
  • direct acting antivirals
  • host-directed antivirals
  • drug-resistant viruses

Published Papers (4 papers)

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Research

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Open AccessArticle
Combination Regimens of Favipiravir Plus Interferon Alpha Inhibit Chikungunya Virus Replication in Clinically Relevant Human Cell Lines
Microorganisms 2021, 9(2), 307; https://doi.org/10.3390/microorganisms9020307 - 02 Feb 2021
Abstract
Chikungunya virus (CHIKV) is an alphavirus associated with a broad tissue tropism for which no antivirals or vaccines are approved. This study evaluated the antiviral potential of favipiravir (FAV), interferon-alpha (IFN), and ribavirin (RBV) against CHIKV as mono- and combination-therapy in cell lines [...] Read more.
Chikungunya virus (CHIKV) is an alphavirus associated with a broad tissue tropism for which no antivirals or vaccines are approved. This study evaluated the antiviral potential of favipiravir (FAV), interferon-alpha (IFN), and ribavirin (RBV) against CHIKV as mono- and combination-therapy in cell lines that are clinically relevant to human infection. Cells derived from human connective tissue (HT-1080), neurons (SK-N-MC), and skin (HFF-1) were infected with CHIKV and treated with different concentrations of FAV, IFN, or RBV. Viral supernatant was sampled daily and the burden was quantified by plaque assay on Vero cells. FAV and IFN were the most effective against CHIKV on various cell lines, suppressing the viral burden at clinically achievable concentrations; although the degree of antiviral activity was heavily influenced by cell type. RBV was not effective and demonstrated substantial toxicity, indicating that it is not a feasible candidate for CHIKV. The combination of FAV and IFN was then assessed on all cell lines. Combination therapy enhanced antiviral activity in HT-1080 and SK-N-MC cells, but not in HFF-1 cells. We developed a pharmacokinetic/pharmacodynamic model that described the viral burden and inhibitory antiviral effect. Simulations from this model predicted clinically relevant concentrations of FAV plus IFN completely suppressed CHIKV replication in HT-1080 cells, and considerably slowed down the rate of viral replication in SK-N-MC cells. The model predicted substantial inhibition of viral replication by clinical IFN regimens in HFF-1 cells. Our results highlight the antiviral potential of FAV and IFN combination regimens against CHIKV in clinically relevant cell types. Full article
(This article belongs to the Special Issue Recent Advances in Antivirals for Emerging Viruses)
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Open AccessCommunication
SARS-CoV-2 Inhibition by Sulfonated Compounds
Microorganisms 2020, 8(12), 1894; https://doi.org/10.3390/microorganisms8121894 - 30 Nov 2020
Cited by 1
Abstract
Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) depends on angiotensin converting enzyme 2 (ACE2) for cellular entry, but it might also rely on attachment receptors such as heparan sulfates. Several groups have recently demonstrated an affinity of the SARS-CoV2 spike protein for heparan [...] Read more.
Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) depends on angiotensin converting enzyme 2 (ACE2) for cellular entry, but it might also rely on attachment receptors such as heparan sulfates. Several groups have recently demonstrated an affinity of the SARS-CoV2 spike protein for heparan sulfates and a reduced binding to cells in the presence of heparin or heparinase treatment. Here, we investigated the inhibitory activity of several sulfated and sulfonated molecules, which prevent interaction with heparan sulfates, against vesicular stomatitis virus (VSV)-pseudotyped-SARS-CoV-2 and the authentic SARS-CoV-2. Sulfonated cyclodextrins and nanoparticles that have recently shown broad-spectrum non-toxic virucidal activity against many heparan sulfates binding viruses showed inhibitory activity in the micromolar and nanomolar ranges, respectively. In stark contrast with the mechanisms that these compounds present for these other viruses, the inhibition against SARS-CoV-2 was found to be simply reversible. Full article
(This article belongs to the Special Issue Recent Advances in Antivirals for Emerging Viruses)
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Open AccessArticle
Identification of an Antiviral Compound from the Pandemic Response Box that Efficiently Inhibits SARS-CoV-2 Infection In Vitro
Microorganisms 2020, 8(12), 1872; https://doi.org/10.3390/microorganisms8121872 - 26 Nov 2020
Abstract
With over 50 million currently confirmed cases worldwide, including more than 1.3 million deaths, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has a major impact on the economy and health care system. Currently, limited prophylactic or therapeutic intervention options are available [...] Read more.
With over 50 million currently confirmed cases worldwide, including more than 1.3 million deaths, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has a major impact on the economy and health care system. Currently, limited prophylactic or therapeutic intervention options are available against SARS-CoV-2. In this study, 400 compounds from the antimicrobial “pandemic response box” library were screened for inhibiting properties against SARS-CoV-2. An initial screen on Vero E6 cells identified five compounds that inhibited SARS-CoV-2 replication. However, validation of the selected hits in a human lung cell line highlighted that only a single compound, namely Retro-2.1, efficiently inhibited SARS-CoV-2 replication. Additional analysis revealed that the antiviral activity of Retro-2.1 occurs at a post-entry stage of the viral replication cycle. Combined, these data demonstrate that stringent in vitro screening of preselected compounds in multiple cell lines refines the rapid identification of new potential antiviral candidate drugs targeting SARS-CoV-2. Full article
(This article belongs to the Special Issue Recent Advances in Antivirals for Emerging Viruses)
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Review

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Open AccessReview
Convalescent Plasma against COVID-19: A Broad-Spectrum Therapeutic Approach for Emerging Infectious Diseases
Microorganisms 2020, 8(11), 1733; https://doi.org/10.3390/microorganisms8111733 - 05 Nov 2020
Abstract
In the lack of an effective vaccine and antiviral treatment, convalescent plasma (CP) has been a promising therapeutic approach in past pandemics. Accumulating evidence in the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic corroborates the safety of CP therapy and preliminary [...] Read more.
In the lack of an effective vaccine and antiviral treatment, convalescent plasma (CP) has been a promising therapeutic approach in past pandemics. Accumulating evidence in the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic corroborates the safety of CP therapy and preliminary data underline the potential efficacy. Recently, the Food and Drug Administration (FDA) permitted CP therapy for coronavirus disease 2019 (COVID-19) patients under the emergency use authorization, albeit additional clinical studies are still needed. The imminent threat of a second or even multiple waves of COVID-19 has compelled health authorities to delineate and calibrate a feasible preparedness algorithm for deploying CP as an immediate therapeutic intervention. The success of preparedness programs depends on the interdisciplinary actions of multiple actors in politics, science, and healthcare. In this review, we evaluate the current status of CP therapy for COVID-19 patients and address the challenges that confront the implementation of CP. Finally, we propose a pandemic preparedness framework for future waves of the COVID-19 pandemic and unknown pathogen outbreaks. Full article
(This article belongs to the Special Issue Recent Advances in Antivirals for Emerging Viruses)
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