Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Specifically, Coronavirus is one of the main pathogens that mainly target the human respiratory system. The lower respiratory tract is the main target of sars-cov-2 infection. Besides, the early stage of COVID-19 often shows a significant decrease in CD4⁺ and CD8⁺ T cell subsets. Moreover, due to the rapid replication of the virus, proinflammatory cytokines, chemokine responses, and inflammatory cell infiltration increased dramatically in 7-10 days. Furthermore, Remdesivir is a promising antiviral drug and works by inhibiting the activity of RNA dependent RNA polymerase (RdRp). GS-441524 is a feline infectious peritonitis virus (FIPV) inhibitor and a predominant metabolite of Remdesivir that is superior to Remdesivir against COVID-19.

GS-441524, a FIPV inhibitor, is a predominant metabolite of Remdesivir and superior to Remdesivir against COVID-19.

But, how does GS-441524 protect against COVID-19? Let’s discuss it in detail. In the beginning, GS-441524 is a predominant metabolite of Remdesivir and superior to Remdesivir against COVID-19. Meanwhile, GS-441524 shows comparable efficacy in cell-based models of primary human lung and cat cells infected with the coronavirus. GS-441524 could strongly inhibit feline infectious peritonitis virus (FIPV), with an EC₅₀of 0.78 μM.

In the second place, Remdesivi of IV injection in NHP results in GS-441524 being present in serum at concentrations 1000-fold higher than Remdesivir throughout a 7-day treatment course. Nonetheless, different from Remdesivir, the concentration of GS-441524 in serum was higher than the EC50 value required for anti-SARS-CoV infected hae cells.

Last but not the least, GS-441524 is capable of treating cats suffering from feline infectious peritonitis (FIP) with a 96% cure rate. Importantly, coupled with the robust antiviral activity of GS-441524 against FIP, these data compel further investigations into the therapeutic and prophylactic utility of GS-441524 against SARS-CoV-2.

All in all, GS-441524, a FIPV inhibitor, is a predominant metabolite of Remdesivir and superior to Remdesivir against COVID-19.

References:

Victoria C. Yan, et al. ACS Med. Chem. Lett. 2020.