Remdisivir – Mechanism of action against viruses
Remdisivir, an anti-viral medication a.l.*, shows activity against Ebola, Severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome (MERS-CoV), and Covid-19 or SARS-CoV-2 (significantly better than placebo).
In the body, remdisivir transforms into GS-704277 with the help of cellular hydrolases. GS-704277 transforms into GS-441524-MP with the help of phosphoramidase. GS-441524-MP either transforms into GS-441524 with the help of nucleotidase, or into GS-443902 with the help of nucleotide kinases. Both GS-441524 and GS-443902 inhibit Viral RNA-dependent, RNA polymerase (RdRp) leading to inhibition of RNA replication that stops the viruses.
Glossary:
Cellular hydrolases: A hydrolase is an enzyme that breaks a chemical bond using water.
GS-441524: A parent nucleoside analog of remdesivir.
GS-441524-MP: A nucleoside analog monophosphate.
GS-443902: An active triphosphate metabolite – GS-441524 triphosphate.
GS-704277: An intermediate metabolite
Nucleotidase: An enzyme catalyzing the hydrolysis of a nucleotide into a nucleoside and a phosphate.
Nucleotide kinases: Enzymes involved in the production of triphosphates.
Phosphoramidase: An enzyme that cleaves the phosphoramide bond.
Viral RNA-dependent, RNA polymerase (RdRp): An enzyme that catalyzes RNA replication from an RNA template.
Source:
Pruijssers, A. J., George, A. S., Schäfer, A., Leist, S. R., Gralinksi, L. E., Dinnon III, K. H., … & Lu, X. (2020). Remdesivir inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in mice. Cell reports, 107940. DOI:https://doi.org/10.1016/j.celrep.2020.107940
Other Reading:
Dictionary of Pharmacological Agents a.l.*
Molecular Biology of the SARS-Coronavirus (2014-11-14) a.l.*
SARS- and Other Coronaviruses: Laboratory Protocols (Methods in Molecular Biology) a.l.*
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