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Advances in Antiviral Agents against SARS-CoV-2 and Its Variants 2nd...
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Advances in Antiviral Agents against SARS-CoV-2 and Its Variants 2nd Edition

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: closed (17 January 2024) | Viewed by 18549

Special Issue Editor

Prof. Dr. Francesca Esposito

E-Mail Website
Guest Editor
Dipartimento di Scienze della Vita e dell’Ambiente, University of Cagliari, Monserrato, 09042 Cagliari, CA, Italy
Interests: severe acute respiratory syndrome coronaviruses (SARS-CoV-2, SARS-CoV-1); Middle East respiratory syndrome coronaviruses (MERS-CoV); human immunodeficiency virus (HIV-1); hepatitis C virus; ebola virus; endogenous retroviruses; viral enzymes; inhibition and characterization of the mechanism of action of different viral targets
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with 610 million reported cases and 6.5 million deaths, represents the worst pandemic in the last 100 years. Since 2020, in order to find effective treatments that can contain and limit infections, the scientific community has stepped up efforts to identify cures for COVID-19 at an unprecedented speed, with huge achievements being made in molecular virology, biological screening platforms, and drug discovery. In parallel with the search for drugs, several vaccines have been validated, which have proven effective in containing the spread of the pandemic. Despite the doses of vaccines, most of the population has been infected with the virus, often showing mild or severe symptoms of the infection. The third dose of the vaccine was needed to counter the emerging viral variants. Although part of the SARS-CoV-2 biology has been characterized in these two years and some drugs have been approved for treatment, progress should continue to be made, with regard to antiviral agents against SARS-CoV-2 and its variants, for any infections caused by emerging and re-emerging viruses.

Researchers have been following different antiviral strategies targeting viral or host factors. The viral main protease and polymerase are currently the most known viral enzymes that, being highly conserved, hold promise for broad-spectrum inhibitors. Moreover, other nonstructural proteins essential for viral replication are still underexploited, such as the nsp13 helicase/NTPase, the nsp14/nsp16 methyltransferase, and the papain-like protease. In parallel, entry inhibitors targeting spike-mediated viral fusion or host endosomal, or membrane proteases, have demonstrated promising results in a preclinical setting. In general, the field of host-targeting agents represents a research area worthy of being explored.

This Special Issue is focused on Advances in Antiviral Agents against SARS-CoV-2 and its Variants and the development of new therapies, including antivirals and vaccine development.

Prof. Dr. Francesca Esposito
Guest Editor

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
  • antiviral agents
  • viral variants
  • therapies

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Published Papers (8 papers)

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Research

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26 pages, 451 KiB  
Article
Why Certain Repurposed Drugs Are Unlikely to Be Effective Antivirals to Treat SARS-CoV-2 Infections
by Selwyn J. Hurwitz, Ramyani De, Julia C. LeCher, Jessica A. Downs-Bowen, Shu Ling Goh, Keivan Zandi, Tamara McBrayer, Franck Amblard, Dharmeshkumar Patel, James J. Kohler, Manoj Bhasin, Brian S. Dobosh, Vikas Sukhatme, Rabindra M. Tirouvanziam and Raymond F. Schinazi
Viruses 2024, 16(4), 651; https://doi.org/10.3390/v16040651 - 22 Apr 2024
Cited by 2 | Viewed by 2511
Abstract
Most repurposed drugs have proved ineffective for treating COVID-19. We evaluated median effective and toxic concentrations (EC50, CC50) of 49 drugs, mostly from previous clinical trials, in Vero cells. Ratios of reported unbound peak plasma concentrations, (Cmax)/EC [...] Read more.
Most repurposed drugs have proved ineffective for treating COVID-19. We evaluated median effective and toxic concentrations (EC50, CC50) of 49 drugs, mostly from previous clinical trials, in Vero cells. Ratios of reported unbound peak plasma concentrations, (Cmax)/EC50, were used to predict the potential in vivo efficacy. The 20 drugs with the highest ratios were retested in human Calu-3 and Caco-2 cells, and their CC50 was determined in an expanded panel of cell lines. Many of the 20 drugs with the highest ratios were inactive in human Calu-3 and Caco-2 cells. Antivirals effective in controlled clinical trials had unbound Cmax/EC50 ≥ 6.8 in Calu-3 or Caco-2 cells. EC50 of nucleoside analogs were cell dependent. This approach and earlier availability of more relevant cultures could have reduced the number of unwarranted clinical trials. Full article
(This article belongs to the Special Issue Advances in Antiviral Agents against SARS-CoV-2 and Its Variants 2nd Edition)
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15 pages, 2819 KiB  
Article
Fluoxetine and Sertraline Potently Neutralize the Replication of Distinct SARS-CoV-2 Variants
by Laura Thümmler, Nadine Beckmann, Carolin Sehl, Matthias Soddemann, Peer Braß, Maren Bormann, Leonie Brochhagen, Carina Elsner, Nicolas Hoertel, Céline Cougoule, Sandra Ciesek, Marek Widera, Ulf Dittmer, Monika Lindemann, Peter A. Horn, Oliver Witzke, Stephanie Kadow, Markus Kamler, Erich Gulbins, Katrin Anne Becker and Adalbert Krawczykadd Show full author list remove Hide full author list
Viruses 2024, 16(4), 545; https://doi.org/10.3390/v16040545 - 30 Mar 2024
Cited by 1 | Viewed by 2613
Abstract
The pandemic caused by SARS-CoV-2 is still a major health problem. Newly emerging variants and long-COVID-19 represent a challenge for the global health system. In particular, individuals in developing countries with insufficient health care need easily accessible, affordable and effective treatments of COVID-19. [...] Read more.
The pandemic caused by SARS-CoV-2 is still a major health problem. Newly emerging variants and long-COVID-19 represent a challenge for the global health system. In particular, individuals in developing countries with insufficient health care need easily accessible, affordable and effective treatments of COVID-19. Previous studies have demonstrated the efficacy of functional inhibitors of acid sphingomyelinase against infections with various viruses, including early variants of SARS-CoV-2. This work investigated whether the acid sphingomyelinase inhibitors fluoxetine and sertraline, usually used as antidepressant molecules in clinical practice, can inhibit the replication of the former and recently emerged SARS-CoV-2 variants in vitro. Fluoxetine and sertraline potently inhibited the infection with pseudotyped virus-like particles and SARS-CoV-2 variants D614G, alpha, delta, omicron BA.1 and omicron BA.5. These results highlight fluoxetine and sertraline as priority candidates for large-scale phase 3 clinical trials at different stages of SARS-CoV-2 infections, either alone or in combination with other medications. Full article
(This article belongs to the Special Issue Advances in Antiviral Agents against SARS-CoV-2 and Its Variants 2nd Edition)
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15 pages, 2398 KiB  
Article
Evaluation of the Polysaccharide “Immeran” Activity in Syrian hamsters’ Model of SARS-CoV-2
by Liubov Viktorovna Generalova, Denis Pavlovich Laryushkin, Irina Anatolievna Leneva, Anna Valerievna Ivanina, Galina Vladimirovna Trunova, Sergei Vladimirovich Dolinnyi and Evgenii Aleksandrovich Generalov
Viruses 2024, 16(3), 423; https://doi.org/10.3390/v16030423 - 9 Mar 2024
Viewed by 1264
Abstract
COVID-19 is a highly contagious respiratory disease with a high number of lethal cases in humans, which causes the need to search for new therapeutic agents. Polysaccharides could be one of the prospective types of molecules with a large variety of biological activities, [...] Read more.
COVID-19 is a highly contagious respiratory disease with a high number of lethal cases in humans, which causes the need to search for new therapeutic agents. Polysaccharides could be one of the prospective types of molecules with a large variety of biological activities, especially antiviral. The aim of this work was to study the specific antiviral activity of the drug “Immeran” on a model of a new coronavirus infection SARS-CoV-2 in hamsters. Based on the second experiment, intraperitoneal treatment with the drug according to a treatment regimen in doses of 500 and 1000 μg/kg (administration after an hour, then once a day every other day, a total of 3 administrations) was effective, reliably suppressing the replication of the virus in the lungs and, at a dose of 1000 μg/kg, prevented weight loss in animals. In all cases, the treatment stimulated the formation of virus-neutralizing antibodies to the SARS-CoV-2 virus, which suggests that the drug possesses adjuvant properties. Full article
(This article belongs to the Special Issue Advances in Antiviral Agents against SARS-CoV-2 and Its Variants 2nd Edition)
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12 pages, 2337 KiB  
Article
In Vitro Combinatorial Activity of Direct Acting Antivirals and Monoclonal Antibodies against the Ancestral B.1 and BQ.1.1 SARS-CoV-2 Viral Variants
by Lia Fiaschi, Camilla Biba, Ilenia Varasi, Niccolò Bartolini, Chiara Paletti, Federica Giammarino, Francesco Saladini, Maurizio Zazzi and Ilaria Vicenti
Viruses 2024, 16(2), 168; https://doi.org/10.3390/v16020168 - 23 Jan 2024
Viewed by 1856
Abstract
Combination antiviral therapy may be helpful in the treatment of SARS-CoV-2 infection; however, no clinical trial data are available, and combined use of direct-acting antivirals (DAA) and monoclonal antibodies (mAb) has been reported only anecdotally. To assess the cooperative effects of dual drug [...] Read more.
Combination antiviral therapy may be helpful in the treatment of SARS-CoV-2 infection; however, no clinical trial data are available, and combined use of direct-acting antivirals (DAA) and monoclonal antibodies (mAb) has been reported only anecdotally. To assess the cooperative effects of dual drug combinations in vitro, we used a VERO E6 cell-based in vitro system with the ancestral B.1 or the highly divergent BQ.1.1 virus to test pairwise combinations of the licensed DAA, including nirmatrelvir (NRM), remdesivir (RDV) and the active metabolite of molnupiravir (EIDD-1931) as well the combination of RDV with four licensed mAbs (sotrovimab, bebtelovimab, cilgavimab, tixagevimab; tested only with the susceptible B.1 virus). According to SynergyFinder 3.0 summary and weighted scores, all the combinations had an additive effect. Within DAA/DAA combinations, paired scores with the B.1 and BQ.1.1 variants were comparable. In the post hoc analysis weighting synergy by concentrations, several cases of highly synergistic scores were detected at specific drug concentrations, both for DAA/DAA and for RDV/mAb combinations. This was supported by in vitro confirmation experiments showing a more than a linear shift of a drug-effective concentration (IC50) at increasing concentrations of the companion drug, although the effect was prominent with DAA/DAA combinations and minimal or null with RDV/mAb combinations. These results support the cooperative effects of dual drug combinations in vitro, which should be further investigated in animal models before introduction into the clinic. Full article
(This article belongs to the Special Issue Advances in Antiviral Agents against SARS-CoV-2 and Its Variants 2nd Edition)
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7 pages, 969 KiB  
Communication
Comparing the Infectivity of Recent SARS-CoV-2 Omicron Sub-Variants in Syrian Hamsters
by Rana Abdelnabi, Ria Lassaunière, Piet Maes, Birgit Weynand and Johan Neyts
Viruses 2024, 16(1), 122; https://doi.org/10.3390/v16010122 - 14 Jan 2024
Cited by 2 | Viewed by 2233
Abstract
Since the emergence of the first omicron SARS-CoV-2 variant at the end of 2021, several sub-variants have evolved and become predominant in the human population, showing enhanced transmissibility and ability to (partly) escape the adaptive immune response. The XBB sub-variants (e.g., EG.5.1) have [...] Read more.
Since the emergence of the first omicron SARS-CoV-2 variant at the end of 2021, several sub-variants have evolved and become predominant in the human population, showing enhanced transmissibility and ability to (partly) escape the adaptive immune response. The XBB sub-variants (e.g., EG.5.1) have become globally dominant. Besides the XBB sub-variants, a phylogenetically distinct variant, i.e., BA.2.86, is also circulating; it carries several mutations in the spike protein as compared to its parental BA.2 variant. Here, we explored the infectivity of the BA.2.86 and EG.5.1 sub-variants compared to the preceding BA.5 sub-variant in Syrian hamsters. Such preclinical models are important for the evaluation of updated vaccine candidates and novel therapeutic modalities. Following intranasal infection with either variant, throat swabs and lung samples were collected on days 3 and 4 post infection. No significant differences in viral RNA loads in throat swabs were observed between these sub-variants. However, the infectious virus titers in the lungs of EG.5.1- and BA.2.86-infected animals were significantly lower compared to the BA.5-infected ones. The lung pathology scores of animals infected with EG.5.1 and BA.2.86 were also markedly lower than that of BA.5 sub-variant. Together, we show that EG.5.1 and BA.2.86 sub-variants exhibit an attenuated replication in hamsters’ lungs as compared to the BA.5 sub-variant. Full article
(This article belongs to the Special Issue Advances in Antiviral Agents against SARS-CoV-2 and Its Variants 2nd Edition)
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Review

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27 pages, 1245 KiB  
Review
Treating COVID-19 with Medicinal Plants: Is It Even Conceivable? A Comprehensive Review
by Hadi Al-Jamal, Sara Idriss, Rabih Roufayel, Ziad Abi Khattar, Ziad Fajloun and Jean-Marc Sabatier
Viruses 2024, 16(3), 320; https://doi.org/10.3390/v16030320 - 20 Feb 2024
Cited by 2 | Viewed by 5354
Abstract
In 2020, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) challenged the world with a global outbreak that led to millions of deaths worldwide. Coronavirus disease 2019 (COVID-19) is the symptomatic manifestation of this virus, which can range from flu-like symptoms to utter clinical complications [...] Read more.
In 2020, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) challenged the world with a global outbreak that led to millions of deaths worldwide. Coronavirus disease 2019 (COVID-19) is the symptomatic manifestation of this virus, which can range from flu-like symptoms to utter clinical complications and even death. Since there was no clear medicine that could tackle this infection or lower its complications with minimal adverse effects on the patients’ health, the world health organization (WHO) developed awareness programs to lower the infection rate and limit the fast spread of this virus. Although vaccines have been developed as preventative tools, people still prefer going back to traditional herbal medicine, which provides remarkable health benefits that can either prevent the viral infection or limit the progression of severe symptoms through different mechanistic pathways with relatively insignificant side effects. This comprehensive review provides scientific evidence elucidating the effect of 10 different plants against SARS-CoV-2, paving the way for further studies to reconsider plant-based extracts, rich in bioactive compounds, into more advanced clinical assessments in order to identify their impact on patients suffering from COVID-19. Full article
(This article belongs to the Special Issue Advances in Antiviral Agents against SARS-CoV-2 and Its Variants 2nd Edition)
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Other

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2 pages, 171 KiB  
Reply
Reply to Taylor et al. Comment on “Manna et al. SARS-CoV-2 Inactivation in Aerosol by Means of Radiated Microwaves. Viruses 2023, 15, 1443”
by Antonio Manna, Davide De Forni, Marco Bartocci, Nicola Pasculli, Barbara Poddesu, Florigio Lista, Riccardo De Santis, Donatella Amatore, Giorgia Grilli, Filippo Molinari, Alberto Sangiovanni Vincentelli and Franco Lori
Viruses 2023, 15(10), 2111; https://doi.org/10.3390/v15102111 - 18 Oct 2023
Cited by 1 | Viewed by 867
Abstract
SARS-CoV-2 is inactivated in aerosol (its primary mode of transmission) by means of radiated microwaves at frequencies that have been experimentally determined. Such frequencies are best predicted by the mathematical model suggested by Taylor, Margueritat and Saviot. The alignment between such mathematical prediction [...] Read more.
SARS-CoV-2 is inactivated in aerosol (its primary mode of transmission) by means of radiated microwaves at frequencies that have been experimentally determined. Such frequencies are best predicted by the mathematical model suggested by Taylor, Margueritat and Saviot. The alignment between such mathematical prediction and the outcomes of our experiments serves to reinforce the efficacy of the radiated microwave technology and its promise in mitigating the transmission of SARS-CoV-2 in its naturally airborne state. Full article
(This article belongs to the Special Issue Advances in Antiviral Agents against SARS-CoV-2 and Its Variants 2nd Edition)
5 pages, 465 KiB  
Comment
Comment on Manna et al. SARS-CoV-2 Inactivation in Aerosol by Means of Radiated Microwaves. Viruses 2023, 15, 1443
by Gavin J. Taylor, Jérémie Margueritat and Lucien Saviot
Viruses 2023, 15(10), 2110; https://doi.org/10.3390/v15102110 - 18 Oct 2023
Cited by 1 | Viewed by 1224
Abstract
In a recent article published in Viruses by Manna et al. [...] Full article
(This article belongs to the Special Issue Advances in Antiviral Agents against SARS-CoV-2 and Its Variants 2nd Edition)
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