Currently, remdesivir is the only antiviral drug approved to treat COVID-19. Its effects on the course of disease are moderate. Many viral diseases, such as HIV and hepatitis C, are treated with drug cocktails. Existing antiviral drugs might make remdesivir more effective in combination.
Two research teams recently screened for antiviral drugs that might increase the effectiveness of remdesivir.
Lo et al. screened a library of drugs for its ability to reduce SARS-CoV-2 viral load in kidney epithelial cells. They found that simeprevir reduces viral load in vitro. Simeprevir is a protease inhibitor that is often combined with sofosbuvir to treat hepatitis C. Simeprevir was even more effective in the in vitro experiment when combined with remdesivir.
Nguyenla et al. added remdesivir to cell cultures of kidney epithelial cells and human lung cells and infected these cells with SARS-CoV-2. They used this remdesivir-treated culture to screen a large library of FDA-approved drugs for compounds that reduce a proxy measure of viral load. The team chose the twenty most promising drugs to validate in human lung cell culture, which they tested for viral load.
The drugs velpatasvir and elbasvir reduced viral load. Both velpatasvir and elbasvir are used as parts of drug cocktails to treat hepatitis C. Velpatasvir is used with sofosbuvir and elbasvir is used with grazoprevir. The research team then tested the velpatasvir/sofosbuvir and elbasvir/grazoprevir cocktails with remdesivir in lung cell culture; the three-drug cocktails were even more effective that the pairs.
These results support the idea that COVID-19 could be better treated with cocktails of antiviral drugs.
Lo HS, Hui KPY, Lai HM, et al. Simeprevir potently suppresses SARS-CoV-2 replication and synergizes with remdesivir. ACS Central Science. 2021 May 26;7(5): 792-802. doi: 10.1021/acscentsci.0c01186. PMID: 34075346
Nguyenla X, Wehri E, Dis EV, et al. Discovery of SARS-CoV-2 antiviral synergy between remdesivir and approved drugs in human lung cells. BiorXiv. Preprint. 2020 Sept. http://doi.org/10.1101/2020.09.18.302398