Remdesivir (GS-5734)

L-Alanine, N-[(S)-hydroxyphenoxyphosphinyl]-, 2-ethylbutyl ester, 6-ester with 2-C-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-2,5-anhydro-D-altrononitrile;2-ethylbutyl (2S)-2-[[[(2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxyoxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate

GS 5734, also known as remdesivir is a nucleoside prodrug with broad spectrum antiviral activity against RNA viruses. As remdesivir / GS 5734 is a prodrug, it requires to be triphosphorylated by cellular kinases in order to compete with ATP for incorporation in newly replicated viral RNA. A major benefit of remdesivir in comparison with other antiviral nucleoside analogs is its resistance to proofreading exonucleases, which occur in coronaviruses. This means remdesivir can overcome the repair mechanism and preserve its antiviral activity. Remdesivir was reported to have a therapeutic as well as prophylactic efficacy in a mouse model infected with SARS-CoV-1.  

Remdesivir (CRM) is a certified reference material categorized as an antiviral. Remdesivir is a prodrug form of the antiviral nucleoside analog GS-441524.1,2 Following intravenous dosing in the mouse, it is distributed to the lungs and liver, among other organs. Upon entry into cells, remdesivir is rapidly and completely metabolized into a nucleoside monophosphate form, which is further metabolized to an active nucleoside triphosphate that induces RNA chain termination and inhibits viral polymerases. It reduces the production of severe acute respiratory coronavirus 2 (SARS-CoV-2) in vitro and reduces lung viral titers and lung hemorrhage, as well as improves pulmonary function, in mice infected with a chimeric SARS-CoV encoding the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). Formulations containing remdesivir have been used in the treatment of COVID-19. This product is intended for use in analytical research applications. This product is also available as a general research tool.

Remdesivir is a prodrug form of the antiviral nucleoside analog GS-441524.1,2 Upon entry into cells, remdesivir is metabolized into a nucleoside monophosphate form, which is further metabolized to an active nucleoside triphosphate that induces RNA chain termination and inhibits viral polymerases. Remdesivir reduces viral titers in primary human airway epithelial (HAE) cells infected with Middle East respiratory syndrome coronavirus (MERS-CoV) or severe acute respiratory syndrome CoV (SARS-CoV; EC50s = 0.074 and 0.069 µM, respectively). It reduces infectious virus production in SARS-CoV-2-infected HAE cells (EC50 = 10 nM). In vivo, remdesivir (25 and 50 mg/kg) reduces lung viral titers and prevents weight loss in a mouse model of SARS-CoV infection. Remdesivir (25 mg/kg) also reduces lung viral titers and lung hemorrhage and improves pulmonary function in mice infected with a chimeric SARS-CoV encoding the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). Formulations containing remdesivir have been used in the treatment of COVID-19.

Novel inhibitor of the replication of several taxonomically diverse RNA viruses such as Middle East respiratory syndrome virus, Ebola virus, Lassa fever virus, Junin virus and respiratory syncytial virus, while having low cytotoxicity in a wide-range of cell lines

Remdesivir, or GS-5734, is an adenosine triphosphate analog first described in the literature in 2016 as a potential treatment for Ebola. But it has shown to attenuate viral loads of a number of RNA viruses including respiratory syncytial virus (RSV) and β-coronaviruses such as SARS-CoV, MERS-CoV, and the causative agent of COVID-19, SARS-CoV-2. Remdesivir is metabolized within cells into an alanine metabolite (GS-704277), further processed into the monophosphate derivative and ultimately into the active nucleoside triphosphate derivative. The active triphosphate is in fact a triphosphate of GS-441524 (C-nucleoside, with ribose connected to the nucleobase via a bond formed between two carbons) that is a final product of the remdesivir activation. The main mechanism of the activity of remdesivir is based on the similarity of its active metabolite triphosphate to a natural substrate necessary for RNA synthesis—adenosine triphosphate. The active molecule affects the activity of viral RNA-dependent RNA polymerase in COVID-19-infected cells. Remdesivir inhibits active sites in both COVID-19 enzymes (RNA-dependent RNA polymerase and exonuclease).