Wednesday, March 25, 2020

COVID-19: Remdesivir (GS-5734)

Here is a short post about Remdesivir (GS-5734).

A '-cyano-substituted adenosine nucleotide analog prodrug.

Mechanism of action:
It interferes with the action of viral RNA polymerase and evades proofreading by viral exoribonuclease (ExoN), causing a decrease in viral RNA production. It is unknown whether it terminates RNA chains or causes mutations in them. [1]

It has broad-spectrum antiviral activity against several RNA viruses including -
Severe acute respiratory syndrome coronavirus (SARS-CoV)
The Middle East respiratory syndrome (MERS-CoV)
West African Ebola virus in the epidemic of 2013–2016.
Remdesivir is now a part of several clinical trials for SARS-CoV-2

Compassionate use: In addition to clinical trials, remdesivir was allowed for compassionate use for a brief period of time (Allow use the unapproved drug, outside of participation in a formal clinical trial). What lead to this? Read the NEJM article. [2]
On 23 March 2020, access to remdesivir was suspended for compassionate use (excepting cases of critically ill children and pregnant women), for reasons related to supply, citing the need to continue to provide the agent for testing in clinical trials.


[1] Agostini ML, Andres EL, Sims AC, et al. Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease. mBio. 2018;9(2):e00221-18. Published 2018 Mar 6. doi:10.1128/mBio.00221-18
[2] Holshue, M. L. et al. First Case of 2019 Novel coronavirus in the United States. N. Engl. J. Med. (2020).

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