Remdesivir is a broad-spectrum antiviral developed by Gilead Sciences. Remdesivir is a prodrug, and upon entry into cells, it is metabolized into the nuceotide triphosphate GS-441524.
Remdesivir was investigated for activity for Ebola virus, but it was found to have activity against the coronavirus (CoV) family of viruses including severe acute repiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome (MERS-CoV), and in vitro activity against SARS-CoV2.
|Mechanism of Action||Remdesivir is a prodrug that is converted in vivo into GS-441524 monophosphate, a ribonucleotide analog, via actions of esterases and phosphoramidase. This in turn is futher phosphorylated to it active metabolite triphosphate by nucleoside-phosphate kinases. The active metabolite of Remdesivir interferes with the action of viral RNA-dependent RNA polymerase and evades proofreading by viral exoribonuclease (ExoN), causing a decrease in viral RNA production. For the RNA-Dependent RNA Polymerase of MERS-CoV, SARS-CoV-1, and SARS-CoV-2 arrest of RNA synthesis occurs after incorporation of three additional nucleotide, thus Remdesivir is classified as a delayed chain terminator. |
Remdesivir is highly effective in the control of 2019-nCoV (COVID-19) infection in vitro.
|Spectrum||Remdesivir was found to have activity against the coronavirus (CoV) family of viruses including severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome (MERS-CoV), and in vitro activity against SARS-CoV2.|
|Microbiology Applications||Remedesivir has EC50s of 74 nM for SARS-CoV and MERS-CoV in HAE cells, and 30 nM for murine hepatitis virus in delayed brain tumor cells.|
|References||Agostini ML (2018) Coronavirus susceptibility to the antiviral Remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. mBio 9 (2) e00221-18 |
Wang M et et al (2020) Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro.
Warren TK et al (2016) Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature. 531(7594): 381–5