Current knowledge about the antivirals remdesivir (GS-5734) and GS-441524 as therapeutic options for coronaviruses

Abstract

Recent international epidemics of coronavirus-associated illnesses underscore the urgent medical and public health need for vaccine development and regulatory body approved therapies. In particular, the current coronavirus disease 2019 (COVID-19) pandemic has quickly intensified interest in developing treatment options to mitigate impact on human life. Remdesivir (GS-5734™) is a broad-spectrum antiviral drug that is now being tested as a potential treatment for COVID-19 in international, multi-site clinical trials. Currently available evidence about the antiviral effects of remdesivir against coronaviruses is primarily based on in vitro and in vivo studies (including some on a chemically related compound, GS-441524™), which have demonstrated largely favorable findings. As the pandemic progresses, information from human compassionate use cases will continue to accumulate before the clinical trials are concluded. It is imperative for public health practitioners and the One Health community to stay up to date on the most promising potential therapeutic options that are under investigation. Thus, the purpose of this review is to synthesize the knowledge to date about remdesivir as a therapeutic option for coronaviruses, with a special focus on information relevant to the One Health community.

Discovery of potential multi-target-directed ligands by targeting host-specific SARS-CoV-2 structurally conserved main protease

“…RdRp is a primary target for nucleotide analog antiviral inhibitors such as Remdesivir, a drug under evaluation for SARS-CoV2 infection in clinics Imbert et al, 2006). Remdesivir, a nucleotide analog, has shown broad-spectrum antiviral activities, and preclinical studies have also shown promising human safety data (Amirian & Levy, 2020;Dong et al, 2020). Recently, a report suggested that the significant inhibition of RdRp of SARS-CoV-2 by Remdesivir, and clinical studies for the same are ongoing to evaluate the efficacy of this molecule in the COVID-19 patients (www.clinicaltrials.gov;Study No: NCT04280705).…”

Development of Remdesivir as a Dry Powder for Inhalation by Thin Film Freezing

“…Remdesivir is a monophosphoramide prodrug that is intracellularly metabolized into an adenosine analog (GS-441524) [4]. Both GS-441524 and remdesivir are metabolized into the active nucleoside triphosphate (GS-443902) by the host [5]. The adenosine nucleoside analog can inhibit viral RNA polymerases, evade proofreading by viral exonucleases, and subsequently decreases viral RNA production [4].…”

Remdesivir in covid-19

“…Coronaviruses enter host cells by binding to and fusing with cell membranes. Once inside, they subvert the host cell’s machinery to replicate, using the virus’s RNA dependent RNA polymerase (RdRp) 2. This non-structural protein is highly conserved among different strains, making it a potentially attractive drug target.…”