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Mechanism of Action: RNA-dependent RNA polymerase (RdRp) inhibition

Remdesivir, is an antiviral medication being developed by Gilead Sciences for the treatment for Ebola virus disease. Animal studies have found it to be active against SARS and MERS viruses. Post the outbreak of COVID-19 pandemic in China, Gilead began laboratory testing of Remdesivir against SARS-CoV-2 in January 2020. Currently, phase-3 clinical trials are underway for Remdesivir to treat COVID-19 patients. The pro-drug (Remdesivir) is metabolized to active molecule (GS-441524). GS-441524, is an adenosine nucleotide analog. Ebola virus studies have shown, Remdesivir inhibited the viral RNA-dependent RNA polymerase (RdRp) enzyme to stop viral genome replication and viral RNA production. Remdesivir is Highly selective for Ebola Virus RdRp as compared to human mitochondrial RNA polymerase. Thus, specific targeting of RdRp can be an effective way to neutralize the SARS-CoV-2 infection.

Excelra’s open-access COVID-19 Drug Repurposing Database is a synoptic compilation of ‘Approved’ small molecules and biologics, which can rapidly enter either Phase 2 or 3, or may even be used directly in clinical settings against COVID-19. The database additionally includes information on promising drug candidates that are in various ‘clinical, pre-clinical and experimental’ stages of drug discovery and development.

Supported with referenced literature, we provide mechanistic insights into SARS-CoV-2 biology and disease pathogenesis. We hope that these drug repositioning approaches can help the global biotech and pharma community develop treatments to combat COVID-19.