Synthesis of indole-based ferulic acid derivatives and in vitro evaluation of antiviral activity against SARS-CoV-2.

The search for an effective small molecule against the severe acute respiratory syndrome related coronavirus 2 (SARS-CoV-2) is a challenge that remains even after the end of the Coronavirus disease 2019 (COVID-19) global health emergency. The indole-based ferulic acid derivatives were synthesized in this work and evaluated for their in vitro cytotoxic profiles and anti-SARS-CoV-2 activity. Compounds 1 and 2 decreased the number of genomic copies of SARS-CoV-2 in a dose-dependent manner, with IC₅₀ values of 70.85 µM and 68.28 µM, respectively, with no significant cytotoxicity up to 100 µM against uninfected Vero cells. In order to search for a possible molecular target of these compounds, their activity against the two SARS-CoV-2 cysteine proteases, M^pro and PL^pro, in addition to the human cysteine protease cathepsin L (hCatL) was investigated. However, they did not display significant activity against any of these proteases and, therefore, their mechanism of action remains unclear. Our findings suggest that the activity may be related to antioxidant properties of 1 and 2, since the presence of a phenolic group is critical for the antiviral activity. [ABSTRACT FROM AUTHOR]