What is Remdesivir?
Remdesivir (or GS-5734) is a nucleoside analogue with antiviral activity developed by Gilead Sciences. It inhibits viral RNA replication by incorporating itself in the nascent viral RNA chain. It was originally developed for the treatment of Ebola virus infection, for which it was judged to be less effective than the monoclonal antibody treatments such as REGN-EB3 and mAb114. It is not currently available for commercial use anywhere in the world.
Remdesivir for Covid 19?
- Despite promising in vitro studies, and encouraging evidence from the compassionate use of remdesivir suggesting a potentially important role in the treatment of severe Covid-19, robust evidence from an RCT is lacking. There are many RCTs now underway whose findings will allow health officials and clinicians to make evidence-based treatment decisions for their patients.
- Remdesivir has demonstrated robust in vitro and in vivo activity on the replication of SARS-CoV and MERS-CoV. In mice infected with SARS-CoV, remdesivir administered therapeutically or prophylactically lead to an improvement in respiratory function with a decrease in pulmonary viral load.
- The RNA-dependent RNA polymerase of SARS-CoV-2, which shares ~97% of its sequence with SARS-CoV was modeled, validated and targeted effectively by remdesivir and several other antiviral drugs (ribavirin, sofosbuvir, galidesivir and tenofovir) in a molecular docking study.
- Remdesivir and chloroquine were also shown to potently block the 2019-nCoV from infecting Vero-E6 cells (monkey kidney lineage-cells) in vitro. Several others, including nafamostat also showed promising inhibitive activity against the 2019-nCoV.
- In patients hospitalized with severe Covid-19, with a median symptom duration of 12 days, and with more than half on mechanical ventilation, IV remdesivir (compassionate use) was started. Outcomes were evaluated 18 days after remdesivir treatment onset (total of 53 patients evaluated).
- There was a 68% improvement in oxygen-support class, and 57% of patients on mechanical ventilation were extubated. There was an overall mortality of 13% and 18% for those on mechanical ventilation.
Remdesivir was available through a compassionate program in mechanically ventilated patients with Covid-19 not meeting any of the exclusion criteria. Gilead suspended the availability of Remdesivir through the compassionate program, and is now available only through their expanded access program.
- Grein J et al. Compassionate use of remdesivir for patients with severe Covid-19. N Engl J Med 2020 Apr 10; [e-pub]. (https://doi.org/10.1056/NEJMoa2007016)
- Wang M, Cao R, Zhang L, et coll. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020. DOI: 10.1038/s41422-020-0282-0
- Agostini ML, Andres EL, Sims AC, et coll. Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease. mBio. 2018 Mar 6;9(2). DOI: 10.1128/mBio.00221-18. https://mbio.asm.org/content/9/2/e00221-18.executive-summary
- A.A. Elfiky, Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study, Life Sciences (2020), https://doi.org/10.1016/j.lfs.2020.117592