Remdesivir (GS-5734)

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Background

Remdesivir (GS-5734) is an antiviral nucleoside analogue that inhibits murine hepatitis virus (MHV) with similar EC50 as SARS-CoV and MERS-CoV.
Coronaviruses (CoVs) are positive-sense, single-stranded RNA viruses that infect a wide range of animal hosts. In humans, CoVs were recognized as typically causing colds and pneumonia until the emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 from zoonotic sources.
GS-5734 is the monophosphoramidate prodrug of the C-adenosine nucleoside analogue GS-441524. In delayed brain tumor (DBT) cells infected with MHV, GS-5734 inhibited MHV more potently than GS-441524, with a GS-5734 EC50 of 0.03 μM. Furthermore, EC50 values were determined after treatment with GS-441524 and GS-5734 in SARS-CoV- and MERS-CoV-infected primary human airway epithelial cell (HAE) cultures. Mean EC50 values for both viruses were approximately 0.86 μM for GS-441524 and 0.074 μM for GS-5734.
In vivo, GS-5734-resistant SARS-CoV is attenuated in its ability to cause disease and replicates less efficiently than WT virus in robust mouse models of human SARS-CoV disease. Moreover, Remdesivir (GS-5734) is in clinical trail for the treatment of people with Ebola Virus disease.

Reference:
Agostini ML, Andres EL, Sims AC, Graham RL, Sheahan TP, Lu X, Smith EC, Case JB, Feng JY, Jordan R, Ray AS, Cihlar T, Siegel D, Mackman RL, Clarke MO, Baric RS, Denison MR. Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease. mBio. 2018 Mar 6;9(2). PMID: 29511076.