Remdisivir – Mechanism of action against viruses

covid 19, coronavirus, remdisivir

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.*

*affiliate link

Usman Zafar Paracha

Usman Zafar Paracha is a sort of entrepreneur. He is the author of "Color Atlas of Statistics", and the owner of an Android game "Faily Rocket."

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