Clinical effectiveness of molnupiravir in patients with COVID-19 undergoing haemodialysis.

BACKGROUND: Molnupiravir is an essential oral antiviral agent against coronavirus disease 2019 (COVID-19); however, its real-world effectiveness has not been evaluated in patients undergoing haemodialysis (HD). METHODS: This multi-centre retrospective study, involving 225 patients undergoing HD with initially mild or asymptomatic COVID-19, was conducted to compare the risks of 30-day COVID-19-related acute care visits between patients receiving and not receiving molnupiravir. Patients who received molnupiravir were stratified by rapid antigen detection (RAD) test results on day 7 after disease onset to assess whether rapid molnupiravir introduction accelerated viral clearance. RESULTS: Thirty-day COVID-19-related acute care visits were reported in 9.41% and 21.74% of the molnupiravir and control groups, respectively, and use of molnupiravir markedly reduced the risk of acute care visits after adjusting for baseline characteristics via propensity score weighting [hazard ratio 0.218, 95% confidence interval (CI) 0.074-0.642; P=0.006]. The tolerability of molnupiravir in the enrolled patients was generally acceptable, with only 11.88% of molnupiravir users reporting mild adverse events. Moreover, rapid initiation of molnupiravir within 1 day of COVID-19 onset was an independent predictor of conversion to a negative RAD test result on day 7 after disease onset (odds ratio 6.207, 95% CI 2.509-15.358; P<0.001). CONCLUSIONS: Molnupiravir is well tolerated and decreases the medical needs in patients with COVID-19 undergoing HD. Furthermore, the rapid initiation of molnupiravir accelerates viral clearance in patients with COVID-19 undergoing HD. These findings highlight the therapeutic role of molnupiravir for this vulnerable population.

Hypothesis of a potential antiviral drug

The approval of mRNA vaccine technique against COVID-19 opens a door to research and the creation of new drugs against different infectious pathologies or even cancer, since for several diseases the therapeutic options are limited, and different viral diseases are treated only symptomatically. For these reasons, this study proposed a hypothesis supported by biological studies, that it provides a theoretical basis for the possible development of a drug that used the mRNA technique and the ribonucleolytic action of a ribonuclease for a possible antiviral therapy, and analyzed a future perspective of this technique in order to provide a bibliographic basis on this hypothesis and motivate researchers to carry out biological studies on this topic.Copyright © 2022, Health Biotechnology and Biopharma. All rights reserved.

A Review of Marine Natural Product Resources with Potential Bioactivity Against SARS-COV-2

The emergence of new pathogenic viruses and the constant outbreak of viral diseases have created an upsurge in novel antiviral agents. Marine natural products are the most unexplored reservoir of novel, biologically active, chemically diverse compounds. A systematic literature review was conducted using PRISMA guidelines, accessing four major databases;PubMed, Science Direct, Scopus, and Google Scholar. Numerous studies supported the robust antiviral activity of marine resources against drug-resistant viruses such as SARS, Ebola, Influenza, and HIV. However, adequate research on marine resources for developing anti-covid therapy is lacking. The aim of the review was to explore the marine resources and their compounds that could lead to developing an effective antiviral drug. We also highlighted the current status of novel compounds against different species of corona family and discussed the future prospects of marine resources against COVID-19 management.Copyright © 2023 the authors.

A Double-Blind, Randomized, Placebo-Controlled, Phase II Clinical Study To Evaluate the Efficacy and Safety of Camostat Mesylate (DWJ1248) in Adult Patients with Mild to Moderate COVID-19.

Although several antiviral agents have become available for coronavirus disease 2019 (COVID-19) treatment, oral drugs are still limited. Camostat mesylate, an orally bioavailable serine protease inhibitor, has been used to treat chronic pancreatitis in South Korea, and it has an in vitro inhibitory potential against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study was a double-blind, randomized, placebo-controlled, multicenter, phase 2 clinical trial in mild to moderate COVID-19 patients. We randomly assigned patients to receive either camostat mesylate (DWJ1248) or placebo orally for 14 days. The primary endpoint was time to clinical improvement of subject symptoms within 14 days, measured using a subjective 4-point Likert scale. Three hundred forty-two patients were randomized. The primary endpoint was nonsignificant, where the median times to clinical improvement were 7 and 8 days in the camostat mesylate group and the placebo group, respectively (hazard ratio [HR] = 1.09; 95% confidence interval [CI], 0.84 to 1.43; P = 0.50). A post hoc analysis showed that the difference was greatest at day 7, without reaching significance. In the high-risk group, the proportions of patients with clinical improvement up to 7 days were 45.8% (50/109) in the camostat group and 38.4% (40/104) in the placebo group (odds ratio [OR] = 1.33; 95% CI, 0.77 to 2.31; P = 0.31); the ordinal scale score at day 7 improved in 20.0% (18/90) of the camostat group and 13.3% (12/90) of the placebo group (OR = 1.68; 95% CI, 0.75 to 3.78; P = 0.21). Adverse events were similar in the two groups. Camostat mesylate was safe in the treatment of COVID-19. Although this study did not show clinical benefit in patients with mild to moderate COVID-19, further clinical studies for high-risk patients are needed. (This trial was registered with ClinicalTrials.gov under registration no. NCT04521296).

Antiviral Activity of Micafungin and Its Derivatives against SARS-CoV-2 RNA Replication.

Echinocandin antifungal drugs, including micafungin, anidulafungin, and caspofungin, have been recently reported to exhibit antiviral effects against various viruses such as flavivirus, alphavirus, and coronavirus. In this study, we focused on micafungin and its derivatives and analyzed their antiviral activities against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The micafungin derivatives Mi-2 and Mi-5 showed higher antiviral activity than micafungin, with 50% maximal inhibitory concentration (IC50) of 5.25 and 6.51 µM, respectively (3.8 to 4.7-fold stronger than micafungin) and 50% cytotoxic concentration (CC50) of >64 µM in VeroE6/TMPRSS2 cells. This high anti-SARS-CoV-2 activity was also conserved in human lung epithelial cell-derived Calu-3 cells. Micafungin, Mi-2, and Mi-5 were suggested to inhibit the intracellular virus replication process; additionally, these compounds were active against SARS-CoV-2 variants, including Delta (AY.122, hCoV-19/Japan/TY11-927/2021), Omicron (BA.1.18, hCoV-19/Japan/TY38-873/2021), a variant resistant to remdesivir (R10/E796G C799F), and a variant resistant to casirivimab/imdevimab antibody cocktail (E406W); thus, our results provide basic evidence for the potential use of micafungin derivatives for developing antiviral agents.

Efficacy of copper blend coatings in reducing SARS-CoV-2 contamination.

SARS-CoV-2 is a highly infectious virus and etiologic agent of COVID-19, which is spread by respiratory droplets, aerosols, and contaminated surfaces. Copper is a known antiviral agent, and has resulted in successful reduction of pathogens and infections by 83-99.9% when coated on surfaces in intensive care units. Additionally, copper has been shown to inactivate pathogens such as Coronavirus 226E, a close relative of SARS-CoV-2. Here, we examine the ability of two copper blends with differing compositions to inactivate SARS-CoV-2 virus at different time points. Copper Blend 2 (75.07% pure copper) was found to significantly reduce (over 50%) the viability of SARS-CoV-2 at 5 min of contact, with at least 98% reduction in recovered virus at 20 min (vs. plastic control). However, Copper Blend 1 (48.26% pure copper), was not found to significantly reduce viability of SARS-CoV-2 at any time point when compared to plastic. This may indicate that there is an important percentage of copper content in materials that is needed to effectively inactivate SARS-CoV-2. Overall, this study shows that over the course of 20 min, coatings made of copper materials can significantly reduce the recovery of infectious SARS-CoV-2 compared to uncoated controls, indicating the effective use of copper for viral inactivation on surfaces. Furthermore, it may suggest higher copper content has stronger antiviral properties. This could have important implications when short turnaround times are needed for cleaning and disinfecting rooms or equipment, especially in strained healthcare settings which are struggling to keep up with demand.

Evaluation of Antiviral Activity of Gemcitabine Derivatives against Influenza Virus and Severe Acute Respiratory Syndrome Coronavirus 2.

Gemcitabine is a nucleoside analogue of deoxycytidine and has been reported to be a broad-spectrum antiviral agent against both DNA and RNA viruses. Screening of a nucleos(t)ide analogue-focused library identified gemcitabine and its derivatives (compounds 1, 2a, and 3a) blocking influenza virus infection. To improve their antiviral selectivity by reducing cytotoxicity, 14 additional derivatives were synthesized in which the pyridine rings of 2a and 3a were chemically modified. Structure-and-activity and structure-and-toxicity relationship studies demonstrated that compounds 2e and 2h were most potent against influenza A and B viruses but minimally cytotoxic. It is noteworthy that in contrast to cytotoxic gemcitabine, they inhibited viral infection with 90% effective concentrations of 14.5-34.3 and 11.4-15.9 µM, respectively, maintaining viability of mock-infected cells over 90% at 300 µM. Resulting antiviral selectivity was comparable to that of a clinically approved nucleoside analogue, favipiravir. The cell-based viral polymerase assay proved the mode-of-action of 2e and 2h targeting viral RNA replication and/or transcription. In a murine influenza A virus-infection model, intraperitoneal administration of 2h not only reduced viral RNA level in the lungs but also alleviated infection-mediated pulmonary infiltrates. In addition, it inhibited replication of severe acute respiratory syndrome virus 2 infection in human lung cells at subtoxic concentrations. The present study could provide a medicinal chemistry framework for the synthesis of a new class of viral polymerase inhibitors.

Molecular docking, molecular dynamics simulation and MM-GBSA studies of the activity of glycyrrhizin relevant substructures on SARS-CoV-2 RNA-dependent-RNA polymerase.

SARS-CoV-2 is the causative agent of Coronavirus Disease (COVID-19), which is a life-threatening disease. The World Health Organization has classified COVID-19 as a severe worldwide public health pandemic due to its high death rate, quick transmission, and lack of medicines. To counteract the recurrence of the severe acute respiratory syndrome, active antiviral medications are urgently required. Glycyrrhizin was documented with activity on different viral proteins, including SARS-CoV-2; in this study, the activity of glycyrrhizin and its substructures (604 molecules) were screened on SARS-CoV-2 RNA-dependent-RNA polymerase using molecular docking, molecular dynamic (MD) simulation, and MM/GBSA. Sixteen molecules exhibited docking energy higher than -7 kcal/mol; four compounds (10772603, 101088272, 154730753 and glycyrrhizin) showed the highest binding energy, and good stability during MD simulation. The glycyrrhizin compound exhibited favorable docking energy (-7.9 kcal/mol), and it was the most stable complex during MD simulation. The predicted binding free energy of the glycyrrhizin complex was -57 ± 8 kcal/mol. These findings suggest that this molecule, after more validation, could become a good candidate for developing and manufacturing an anti-SARS-CoV-2 medication.Communicated by Ramaswamy H. Sarma.

Hypothesis of a potential antiviral drug

The approval of mRNA vaccine technique against COVID-19 opens a door to research and the creation of new drugs against different infectious pathologies or even cancer, since for several diseases the therapeutic options are limited, and different viral diseases are treated only symptomatically. For these reasons, this study proposed a hypothesis supported by biological studies, that it provides a theoretical basis for the possible development of a drug that used the mRNA technique and the ribonucleolytic action of a ribonuclease for a possible antiviral therapy, and analyzed a future perspective of this technique in order to provide a bibliographic basis on this hypothesis and motivate researchers to carry out biological studies on this topic. Copyright © 2022, Health Biotechnology and Biopharma. All rights reserved.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and nucleotide analog GS-441524 conjugates with potent in vivo efficacy against coronaviruses.

Coronaviruses (CoVs) infect a broad range of hosts, including humans and various animals, with a tendency to cross the species barrier, causing severe harm to human society and fostering the need for effective anti-coronaviral drugs. GS-441524 is a broad-spectrum antiviral nucleoside with potent anti-CoVs activities. However, its application is limited by poor oral bioavailability. Herein, we designed and synthesized several conjugates via covalently binding NSAIDs to 5'-OH of GS-441524 through ester bonds. The ibuprofen conjugate, ATV041, exhibited potent in vitro anti-coronaviral efficacy against four zoonotic coronaviruses in the alpha- and beta-genera. Oral-dosed ATV041 resulted in favorable bioavailability and rapid tissue distribution of GS-441524 and ibuprofen. In MHV-A59 infected mice, ATV041 dose-dependently decreased viral RNA replication and significantly reduced the proinflammatory cytokines in the liver and the lung at 3 dpi. As a result, the MHV-A59-induced lung and liver inflammatory injury was significantly alleviated. Taken together, this work provides a novel drug conjugate strategy to improve oral PK and offers a potent anti-coronaviral lead compound for further studies.

In Silico Screening of Bioactive Compounds from Garcinia mangostana L. Against SARS-CoV-2 via Tetra Inhibitors

The global COVID-19 pandemic caused by SARS-CoV-2 has been the resulted of massive human deaths since early 2020. The purpose of this study was to determine the potential of mangosteen (Garcinia mangostana L.) as an inhibitor of RBD spike, helicase, Mpro, and RdRp activity of SARS-CoV-2 with an in silico approach. The samples were obtained from PubChem and RCSB PDB. Analysis of the similarity of the drug was carried out with the Swiss ADME on the basis of Lipinski rule of five. Prediction of antivirus probabilities was carried out using PASS Online. Molecular screening was performed using PyRx through molecular docking. Discovery Studio was used for visualization. The bioactive compounds with the highest antiviral potential were indicated with the lowest binding affinity to the targeted proteins RBD spike, helicase, Mpro, and RdRp of SARS-CoV-2. The results indicated that mangiferin has the greatest potential as a potential antiviral. However, more research is required to validate the results of these computational predictions. Copyright © 2022 Phcogj.Com.

A bovine antibody possessing an ultralong complementarity-determining region CDRH3 targets a highly conserved epitope in sarbecovirus spike proteins.

Broadly neutralizing antibodies have huge potential as novel antiviral therapeutics due to their ability to recognize highly conserved epitopes that are seldom mutated in viral variants. A subset of bovine antibodies possess an ultralong complementarity-determining region (CDR)H3 that is highly adept at recognizing such conserved epitopes, but their reactivity against Sarbecovirus Spike proteins has not been explored previously. Here, we use a SARS-naïve library to isolate a broadly reactive bovine CDRH3 that binds the receptor-binding domain of SARS-CoV, SARS-CoV-2, and all SARS-CoV-2 variants. We show further that it neutralizes viruses pseudo-typed with SARS-CoV Spike, but this is not by competition with angiotensin-converting enzyme 2 (ACE2) binding. Instead, using differential hydrogen-deuterium exchange mass spectrometry, we demonstrate that it recognizes the major site of vulnerability of Sarbecoviruses. This glycan-shielded cryptic epitope becomes available only transiently via interdomain movements of the Spike protein such that antibody binding triggers destruction of the prefusion complex. This proof of principle study demonstrates the power of in vitro expressed bovine antibodies with ultralong CDRH3s for the isolation of novel, broadly reactive tools to combat emerging pathogens and to identify key epitopes for vaccine development.

Antivirals based on nanomaterials against SARS-CoV-2

In this chapter the use of nanomaterials (e.g., graphene oxide, quantum dots, silver, zinc oxide, and gold nanoparticles) to combat COVID-19 is presented. This chapter does not include nanomaterials used for the release of drugs or antiviral molecules where the nanomaterial is not a part of the antiviral effect. The nanomaterials presented somehow interact with the virus, therefore, having an antiviral effect per se. The chapter first reviews the updated efforts conducted evaluating nanomaterials against SARS-CoV-2. Later, the chapter reviews nanomaterials that have been evaluated against enveloped viruses (e.g., the feline coronavirus, influenza A virus, pseudorabies virus, herpes simplex virus, and respiratory syncytial virus), which could be tested against SARS-CoV-2. Most of the nanomaterials studied thus far are effective at inhibiting viruses when contacting them with the virus before infection. Incipient studies address the use of nanomaterials in therapeutic approaches. Similarly, most studies of nanomaterials against viruses have only been evaluated in vitro. Few studies have been conducted in vivo using mice. Virus inactivation is generally achieved by the interaction of the nanomaterial and the virus through electrostatic, hydrophobic, and affinity interactions. A combination of these interactions could arise depending on the properties of the nanomaterial. In few stances the nanomaterial studied responds to an external stimulation, such as near-infrared irradiation, to inactivate the virus. Finally, some works evaluate or envision the nanomaterials as antiviral agents of surfaces or components of personal protection equipment. © 2022 Elsevier Inc. All rights reserved.

Bioactive Compounds from Purslane (Portulaca oleracea L.) and Star Anise (Illicium verum Hook) as SARS-CoV-2 Antiviral Agent via Dual Inhibitor Mechanism: In Silico Approach

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the COVID-19 pandemic that infects humans and attacks the body's immune system. The purpose of the study was to identify the potential of bioactive compounds in purslane (Portulaca oleracea L.) and star anise (Illicium verum Hook) via a dual inhibitor mechanism against SARS-CoV-2 proteases with an in silico approach. The samples were obtained from PubChem and RSCB PDB. Antivirus probability prediction was performed on PASS Online. Virtual screening was performed with PyRx via molecular docking. Visualization was used by PyMol and Discovery Studio. Compounds with the best antiviral potential are indicated by the low binding affinity value to the target proteins, namely SARS-CoV-2 TMPRSS2 and PLpro. The results showed that purslane luteolin has the best antiviral potential. However, further studies are required to validate this computational prediction. © 2022 Phcogj.Com.

Nutraceutical prospects of Houttuynia cordata against the infectious viruses.

The novel enveloped ß-coronavirus SARS-CoV-2 (COVID-19) has offered a surprising health challenge all over the world. It develops severe pneumonia leading to acute respiratory distress syndrome (ARDS). Like SARS-COV-2, other encapsulated viruses like HIV, HSV, and influenza have also offered a similar challenge in the past. In this regard, many antiviral drugs are being explored with varying degrees of success to combat the associated pathological conditions. Therefore, upon scientific validation & development, these antiviral phytochemicals can attain a futuristic nutraceutical prospect in managing different encapsulated viruses. Houttuynia cordata (HC) is widely reported for activities such as antioxidant, anti-inflammatory, and antiviral properties. The major antiviral bioactive components of HC include essential oils (methyl n-nonyl ketone, lauryl aldehyde, capryl aldehyde), flavonoids (quercetin, rutin, hyperin, quercitrin, isoquercitrin), and alkaloids (norcepharadione B) & polysaccharides. HC can further be explored as a potential nutraceutical agent in the therapy of encapsulated viruses like HIV, HSV, and influenza. The review listed various conventional and green technologies that are being employed to extract potent phytochemicals with diverse activities from the HC. It was indicated that HC also inhibited molecular targets like 3C-like protease (3CLPRO) and RNA-dependent RNA polymerase (RdRp) of COVID-19 by blocking viral RNA synthesis and replication. Antioxidant and hepatoprotective effects of HC have been evident in impeding complications from marketed drugs during antiviral therapies. The use of HC as a nutraceutical is localized within some parts of Southeast Asia. Further technological advances can establish it as a nutraceutical-based functional food against pathogenic enveloped viruses like COVID 19.

Collaborative Referral Model to Achieve Hepatitis C Micro-Elimination in Methadone Maintenance Treatment Patients during the COVID-19 Pandemic.

Although hepatitis C virus (HCV) prevails in patients receiving methadone maintenance treatment (MMT), most do not receive anti-HCV therapy. This single-center observational study aimed to achieve HCV micro-elimination at an MMT center during the COVID-19 pandemic using a collaborative referral model, which comprised a referral-for-diagnosis stage (January 2020 to August 2020) and an on-site-diagnosis stage (September 2020 to January 2021). A multidisciplinary team was established and all MMT center patients were enrolled. HCV micro-elimination was defined as >90% of HCV-infected patients diagnosed and >80% of HCV-viremic patients treated. A total of 305 MMT patients, including 275 (90.2%) anti-HCV seropositive patients, were enrolled. Among 189 HCV-infected patients needing referral, the accumulative percentage receiving HCV RNA testing increased from 93 (49.2%) at referral-for-diagnosis stage to 168 (88.9%) at on-site-diagnosis stage. Among 138 HCV-viremic patients, the accumulative percentage receiving direct-acting antiviral (DAA) therapy increased from 77 (55.8%) at referral-for-diagnosis stage to 129 (93.5%) at on-site-diagnosis stage. We achieved an HCV RNA testing rate of 92.4% (254/275), an HCV treatment rate of 95.8% (203/212) and a sustained virological response rate of 94.1% (191/203). The collaborative referral model is highly effective in HCV RNA testing and HCV treatment uptake among MMT patients, achieving HCV micro-elimination.

Early 3-day course of remdesivir in vaccinated outpatients with SARS-CoV-2 infection. A success story.

A number of treatment options have been evaluated in order to prevent the severe progression of COVID-19 pneumonia eventually in patients with increased risk due to comorbidities. Remdesivir for a 3-day outpatient course has been associated with a significant lower risk of hospitalization or death. A matched-pair retrospective study was conducted in Department of Infectious Diseases of University General Hospital of Alexandroupolis in order to evaluate the role of remdesivir and vaccination in preventing severe clinical outcome. Nonhospitalized vaccinated patients with a 3-day course of remdesivir had a 75% lower possibility of hospitalization and 95% of respiratory failure. Nobody was intubated or died and the duration of hospital stay was limited (4 day s vs. 10 days). Vaccination and a 3-day course of remdesivir in high risk nonhospitalized patients prevented significantly severe clinical progress of COVID-19 pneumonia.

Application of Silver Nanoparticles as a New Alternative Antiviral Agent for SARS-CoV-2: A Review

Background: Today, SARS-CoV-2 (COVID-19), a viral disease caused by the novel coronavirus (a tiny crowned virus), has become one of the threats for human beings all over the world and caused the death of millions of people worldwide. Many vaccines have been developed and administered to people in several countries;however, due to their propensity to create new strains, it appears that curing all corona strains will be challenging. So, it is necessary to identify the structure of the virus, mechanism of action, and its antiviral activities against drugs and other functional materials. Methods: AgNPs have unique physicochemical and antimicrobial properties. This review describes the structure and nature of the virus and the mechanism of action of an antiviral drug such as silver nanoparticles (AgNPs) with the virus. In addition, different methods for synthesis of AgNPs, application of AgNPs as an antiviral agent against influenza virus, human immuno deficiency virus (HIV), herpes simplex virus type 1 (HSV-1), hepatitis B virus (HBV), polio virus, respiratory syncytial virus (RSV), are discussed. Also, the most probable applications and properties of AgNPs that can help prepare it as an antiviral agent are discussed. Results: The use of AgNPs against various viruses, including the coronavirus family, is found to be effective;therefore, it can be considered for the development of antiviral agents, disinfectants, antiviral coated mask, and their therapeutic use against the treatment of novel coronavirus with minimum side effect and great efficiency. Conclusion: AgNPs were successfully used for the treatment of various viral diseases of the coronavirus family such as H1N1, H3N2, influenza, even for SARS and MERS coronaviruses. AgNPs coated masks, disinfectants, fabrics, wipes, and inhalation systems are effective for the inhibition of SARS-CoV-2 infection. Since sanitizers have a temporary effect, the development of some other potential alternatives having low toxicity, ease of use, long lasting efficiency, health cautiousness, minimum side effect, sustainable fabrics is required.

Decavanadate interactions with the elements of the SARS-CoV-2 spike protein highlight the potential role of electrostatics in disrupting the infectivity cycle.

Polyoxidometalates (POMs) exhibit a range of biological properties that can be exploited for a variety of therapeutic applications. However, their potential utility as antivirals has been largely overlooked in the ongoing efforts to identify safe, effective and robust therapeutic agents to combat COVID-19. We focus on decavanadate (V10), a paradigmatic member of the POM family, to highlight the utility of electrostatic forces as a means of disrupting molecular processes underlying the SARS-CoV-2 entry into the host cell. While the departure from the traditional lock-and-key approach to the rational drug design relies on less-specific and longer-range interactions, it may enhance the robustness of therapeutic agents by making them less sensitive to the viral mutations. Native mass spectrometry (MS) not only demonstrates the ability of V10 to associate with the receptor-binding domain of the SARS-CoV-2 spike protein, but also provides evidence that this association disrupts the protein binding to its host cell-surface receptor. Furthermore, V10 is also shown to be capable of binding to the polybasic furin cleavage site within the spike protein, which is likely to decrease the effectiveness of the proteolytic processing of the latter (a pre-requisite for the viral fusion with the host cell membrane). Although in vitro studies carried out with SARS-CoV-2 infected cells identify V10 cytotoxicity as a major factor limiting its utility as an antiviral agent, the collected data provide a compelling stimulus for continuing the search for effective, robust and safe therapeutics targeting the novel coronavirus among members of the POM family.