Drugs against SARS‐CoV‐2: What do we know about their mode of action?

Abstract

The health emergency caused by the recent Covid-19 pandemic highlights the need to identify effective treatments against the virus causing this disease (SARS-CoV-2). The first clinical trials have been testing repurposed drugs that show promising anti-SARS-CoV-2 effects in cultured cells. Although more than 2400 clinical trials are already under way, the actual number of tested compounds is still limited to approximately 20, alone or in combination. In addition, knowledge on their mode of action (MoA) is currently insufficient. Their first results reveal some inconsistencies and contradictory results and suggest that cohort size and quality of the control arm are two key issues for obtaining rigorous and conclusive results. Moreover, the observed discrepancies might also result from differences in the clinical inclusion criteria, including the possibility of early treatment that may be essential for therapy efficacy in patients with Covid-19. Importantly, efforts should also be made to test new compounds with a documented MoA against SARS-CoV-2 in clinical trials. Successful treatment will probably be based on multitherapies with antiviral compounds that target different steps of the virus life cycle. Moreover, a multidisciplinary approach that combines artificial intelligence, compound docking, and robust in vitro and in vivo assays will accelerate the development of new antiviral molecules. Finally, large retrospective studies on hospitalized patients are needed to evaluate the different treatments with robust statistical tools and to identify the best treatment for each Covid-19 stage. This review describes different candidate antiviral strategies for Covid-19, by focusing on their mechanism of action. Highlights • SARS-CoV-2 is a major threat to public health in the absence of drugs and vaccines. • The development of antiviral agents is urgently needed to treat patients with Covid-19 and limit SARS-CoV-2 dissemination.

Virtual screenings of the bioactive constituents of tea, prickly chaff, catechu, lemon, black pepper, and synthetic compounds with the main protease (Mpro) and human angiotensin-converting enzyme 2 (ACE 2) of SARS-CoV-2

“…Favipiravir is one of the antiviral drugs tested against several SARS-CoV-2 envelope proteins [ 80 ]. Favipiravir, a pyrazine carboxamide derivative molecule, works as an antiviral molecule that is a prodrug against RNA viruses.…”

A retrospective comparison of drugs against COVID-19

“…( Eslami and Jalili, 2020 ; Roviello and Roviello, 2020 ) To combat COVID-19 infection, several measures are taken to manage the epidemic. ( Valle et al, 2020 ) The development of a vaccine or a new drug against SARS-CoV-2 is time-consuming. ( Ahsan et al, 2020 ; Amanat and Krammer, 2020 ) Some vaccines show superior preventive efficiency, but are not available for the general population before the fulfilment of preclinical evaluations.…”

6′,6′-Difluoro-aristeromycin is a potent inhibitor of MERS-coronavirus replication

“…Thus far, only remdesivir was approved for emergency treatment of COVID-19 patients in the United States of America, Europe, and Japan. Many drug classes currently are under evaluation as inhibitors of CoV replication, including both compounds directly targeting viral functions, like viral proteases and the RNA polymerase, and host factor-targeting inhibitors (reviewed in (9)(10)(11)(12)).…”