Broad-Spectrum Antivirals of Coronaviruses Replication

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 December 2021) | Viewed by 39965

Special Issue Editor


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Guest Editor
Max von Pettenkofer-Institute, Ludwig-Maximilians-University Munich, 80336 Munich, Germany
Interests: coronaviruses; broad-spectrum antivirals; cyclophilin/calcineurin inhibitors; intraviral and virus-host interactome; coronavirus replication

Special Issue Information

Dear Colleagues,

In light of the emergence of SARS-CoV-2 and, consequently, the COVID-19 pandemic, the scientific world has been unified and relentless in its fight against the disease. This has been illustrated by the unprecedented speed at which vaccinations have been developed and approved. Prophylaxis alone, however, does not spell the end of a pandemic. Now, more than ever, it is imperative that we continue our remarkable progress by developing safe, accessible, and cost-effective methods for treating SARS-CoV-2 infections. Sadly, the countless lives lost to the disease have underlined the glaring lack of tried-and-true treatment options easily available today. Biologics, such as specific commercial antibody cocktails, are largely efficacious, but their accessibility is severely restricted by their costs of production.

The main stages of the SARS-CoV-2 lifecycle comprise the S-protein docking to host receptors, viral entry, gene translation/replication, virion packaging, and shedding. These stages are mirrored and mechanistically conserved in other highly virulent coronaviruses such as SARS-CoV and MERS-CoV. Each of these stages can be therapeutically targeted, and by building upon the already existing knowledge of coronaviruses, drugs can be developed and/or repurposed for the treatment of SARS-CoV-2 and other coronaviruses alike, past, present, or future.

In this Special Issue, we invite researchers around the globe to submit their work on broad-spectrum coronavirus inhibitors. These may comprise directly acting antivirals (S-protein blockers, viral polymerase/protease inhibitors, etc.) or drugs targeting host proteins and pathways relevant to the viral lifecycle. Naturally, such drugs’ effects could extend beyond mildly and highly virulent coronaviruses into other virus families, lending them further value. All manner of work on these topics is welcomed, from proof-of-principle studies to clinical trial data, as well as expert reviews on the topic.

Dr. Albrecht von Brunn
Guest Editor

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Keywords

  • SARS-CoV-2
  • coronaviruses
  • viral entry
  • S-protein
  • anti-CoV biologicals
  • broad-spectrum coronavirus inhibitors
  • antiviral drugs
  • antivirals
  • therapeutics

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Published Papers (6 papers)

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Research

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6 pages, 593 KiB  
Communication
Antiviral Effect of Budesonide against SARS-CoV-2
by Natalie Heinen, Toni Luise Meister, Mara Klöhn, Eike Steinmann, Daniel Todt and Stephanie Pfaender
Viruses 2021, 13(7), 1411; https://doi.org/10.3390/v13071411 - 20 Jul 2021
Cited by 15 | Viewed by 9971
Abstract
Treatment options for COVID-19, a disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, are currently severely limited. Therefore, antiviral drugs that efficiently reduce SARS-CoV-2 replication or alleviate COVID-19 symptoms are urgently needed. Inhaled glucocorticoids are currently being [...] Read more.
Treatment options for COVID-19, a disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, are currently severely limited. Therefore, antiviral drugs that efficiently reduce SARS-CoV-2 replication or alleviate COVID-19 symptoms are urgently needed. Inhaled glucocorticoids are currently being discussed in the context of treatment for COVID-19, partly based on a previous study that reported reduced recovery times in cases of mild COVID-19 after inhalative administration of the glucocorticoid budesonide. Given various reports that describe the potential antiviral activity of glucocorticoids against respiratory viruses, we aimed to analyze a potential antiviral activity of budesonide against SARS-CoV-2 and circulating variants of concern (VOC) B.1.1.7 (alpha) and B.1.351 (beta). We demonstrate a dose-dependent inhibition of SARS-CoV-2 that was comparable between all viral variants tested while cell viability remains unaffected. Our results are encouraging as they could indicate a multimodal mode of action of budesonide against SARS-CoV-2 and COVID-19, which could contribute to an improved clinical performance. Full article
(This article belongs to the Special Issue Broad-Spectrum Antivirals of Coronaviruses Replication)
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18 pages, 2616 KiB  
Article
Antiviral Activity of Vitis vinifera Leaf Extract against SARS-CoV-2 and HSV-1
by Carla Zannella, Rosa Giugliano, Annalisa Chianese, Carmine Buonocore, Giovanni Andrea Vitale, Giuseppina Sanna, Federica Sarno, Aldo Manzin, Angela Nebbioso, Pasquale Termolino, Lucia Altucci, Massimiliano Galdiero, Donatella de Pascale and Gianluigi Franci
Viruses 2021, 13(7), 1263; https://doi.org/10.3390/v13071263 - 29 Jun 2021
Cited by 59 | Viewed by 7681
Abstract
Vitis vinifera represents an important and renowned source of compounds with significant biological activity. Wines and winery bioproducts, such as grape pomace, skins, and seeds, are rich in bioactive compounds against a wide range of human pathogens, including bacteria, fungi, and viruses. However, [...] Read more.
Vitis vinifera represents an important and renowned source of compounds with significant biological activity. Wines and winery bioproducts, such as grape pomace, skins, and seeds, are rich in bioactive compounds against a wide range of human pathogens, including bacteria, fungi, and viruses. However, little is known about the biological properties of vine leaves. The aim of this study was the evaluation of phenolic composition and antiviral activity of Vitis vinifera leaf extract against two human viruses: the Herpes simplex virus type 1 (HSV-1) and the pandemic and currently widespread severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). About 40 phenolic compounds were identified in the extract by HPLC-MS/MS analysis: most of them were quercetin derivatives, others included derivatives of luteolin, kaempferol, apigenin, isorhamnetin, myricetin, chrysoeriol, biochanin, isookanin, and scutellarein. Leaf extract was able to inhibit both HSV-1 and SARS-CoV-2 replication in the early stages of infection by directly blocking the proteins enriched on the viral surface, at a very low concentration of 10 μg/mL. These results are very promising and highlight how natural extracts could be used in the design of antiviral drugs and the development of future vaccines. Full article
(This article belongs to the Special Issue Broad-Spectrum Antivirals of Coronaviruses Replication)
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Review

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11 pages, 2297 KiB  
Review
Mutations and Evolution of the SARS-CoV-2 Spike Protein
by Nicholas Magazine, Tianyi Zhang, Yingying Wu, Michael C. McGee, Gianluca Veggiani and Weishan Huang
Viruses 2022, 14(3), 640; https://doi.org/10.3390/v14030640 - 19 Mar 2022
Cited by 126 | Viewed by 13059 | Correction
Abstract
The SARS-CoV-2 spike protein mediates target recognition, cellular entry, and ultimately the viral infection that leads to various levels of COVID-19 severities. Positive evolutionary selection of mutations within the spike protein has led to the genesis of new SARS-CoV-2 variants with greatly enhanced [...] Read more.
The SARS-CoV-2 spike protein mediates target recognition, cellular entry, and ultimately the viral infection that leads to various levels of COVID-19 severities. Positive evolutionary selection of mutations within the spike protein has led to the genesis of new SARS-CoV-2 variants with greatly enhanced overall fitness. Given the trend of variants with increased fitness arising from spike protein alterations, it is critical that the scientific community understand the mechanisms by which these mutations alter viral functions. As of March 2022, five SARS-CoV-2 strains were labeled “variants of concern” by the World Health Organization: the Alpha, Beta, Gamma, Delta, and Omicron variants. This review summarizes the potential mechanisms by which the common mutations on the spike protein that occur within these strains enhance the overall fitness of their respective variants. In addressing these mutations within the context of the SARS-CoV-2 spike protein structure, spike/receptor binding interface, spike/antibody binding, and virus neutralization, we summarize the general paradigms that can be used to estimate the effects of future mutations along SARS-CoV-2 evolution. Full article
(This article belongs to the Special Issue Broad-Spectrum Antivirals of Coronaviruses Replication)
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11 pages, 435 KiB  
Review
Cellular Uptake and Intracellular Phosphorylation of GS-441524: Implications for Its Effectiveness against COVID-19
by Henrik Berg Rasmussen, Gesche Jürgens, Ragnar Thomsen, Olivier Taboureau, Kornelius Zeth, Poul Erik Hansen and Peter Riis Hansen
Viruses 2021, 13(7), 1369; https://doi.org/10.3390/v13071369 - 14 Jul 2021
Cited by 12 | Viewed by 3568
Abstract
GS-441524 is an adenosine analog and the parent nucleoside of the prodrug remdesivir, which has received emergency approval for treatment of COVID-19. Recently, GS-441524 has been proposed to be effective in the treatment of COVID-19, perhaps even being superior to remdesivir for treatment [...] Read more.
GS-441524 is an adenosine analog and the parent nucleoside of the prodrug remdesivir, which has received emergency approval for treatment of COVID-19. Recently, GS-441524 has been proposed to be effective in the treatment of COVID-19, perhaps even being superior to remdesivir for treatment of this disease. Evaluation of the clinical effectiveness of GS-441524 requires understanding of its uptake and intracellular conversion to GS-441524 triphosphate, the active antiviral substance. We here discuss the potential impact of these pharmacokinetic steps of GS-441524 on the formation of its active antiviral substance and effectiveness for treatment of COVID-19. Available protein expression data suggest that several adenosine transporters are expressed at only low levels in the epithelial cells lining the alveoli in the lungs, i.e., the alveolar cells or pneumocytes from healthy lungs. This may limit uptake of GS-441524. Importantly, cellular uptake of GS-441524 may be reduced during hypoxia and inflammation due to decreased expression of adenosine transporters. Similarly, hypoxia and inflammation may lead to reduced expression of adenosine kinase, which is believed to convert GS-441524 to GS-441524 monophosphate, the perceived rate-limiting step in the intracellular formation of GS-441524 triphosphate. Moreover, increases in extracellular and intracellular levels of adenosine, which may occur during critical illnesses, has the potential to competitively decrease cellular uptake and phosphorylation of GS-441524. Taken together, tissue hypoxia and severe inflammation in COVID-19 may lead to reduced uptake and phosphorylation of GS-441524 with lowered therapeutic effectiveness as a potential outcome. Hypoxia may be particularly critical to the ability of GS-441524 to eliminate SARS-CoV-2 from tissues with low basal expression of adenosine transporters, such as alveolar cells. This knowledge may also be relevant to treatments with other antiviral adenosine analogs and anticancer adenosine analogs as well. Full article
(This article belongs to the Special Issue Broad-Spectrum Antivirals of Coronaviruses Replication)
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12 pages, 2292 KiB  
Review
NSP16 2′-O-MTase in Coronavirus Pathogenesis: Possible Prevention and Treatments Strategies
by Li-Jen Chang and Tsung-Hsien Chen
Viruses 2021, 13(4), 538; https://doi.org/10.3390/v13040538 - 24 Mar 2021
Cited by 26 | Viewed by 3639
Abstract
Several life-threatening viruses have recently appeared, including the coronavirus, infecting a variety of human and animal hosts and causing a range of diseases like human upper respiratory tract infections. They not only cause serious human and animal deaths, but also cause serious public [...] Read more.
Several life-threatening viruses have recently appeared, including the coronavirus, infecting a variety of human and animal hosts and causing a range of diseases like human upper respiratory tract infections. They not only cause serious human and animal deaths, but also cause serious public health problems worldwide. Currently, seven species are known to infect humans, namely SARS-CoV-2, MERS-CoV, SARS-CoV, HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1. The coronavirus nonstructural protein 16 (NSP16) structure is similar to the 5′-end capping system of mRNA used by eukaryotic hosts and plays a vital role in evading host immunity response and protects the nascent viral mRNA from degradation. NSP16 is also well-conserved among related coronaviruses and requires its binding partner NSP10 to activate its enzymatic activity. With the continued threat of viral emergence highlighted by human coronaviruses and SARS-CoV-2, mutant strains continue to appear, affecting the highly conserved NSP16: this provides a possible therapeutic approach applicable to any novel coronavirus. To this end, current information on the 2′-O-MTase activity mechanism, the differences between NSP16 and NSP10 in human coronaviruses, and the current potential prevention and treatment strategies related to NSP16 are summarized in this review. Full article
(This article belongs to the Special Issue Broad-Spectrum Antivirals of Coronaviruses Replication)
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Other

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1 pages, 440 KiB  
Correction
Correction: Magazine et al. Mutations and Evolution of the SARS-CoV-2 Spike Protein. Viruses 2022, 14, 640
by Nicholas Magazine, Tianyi Zhang, Yingying Wu, Michael C. McGee, Gianluca Veggiani and Weishan Huang
Viruses 2023, 15(9), 1787; https://doi.org/10.3390/v15091787 - 23 Aug 2023
Viewed by 844
Abstract
In the original publication [...] Full article
(This article belongs to the Special Issue Broad-Spectrum Antivirals of Coronaviruses Replication)
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