New chalcone derivatives as effective against SARS-CoV-2 agent

Aims Flavonoids and related compounds, such as quercetin-based antiviral drug Gene-Eden-VIR/Novirin, inhibit the protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The alkylated chalcones isolated from Angelica keiskei inhibit SARS-CoV proteases. In this study, we aimed to compare the anti-SARS CoV-2 activities of both newly synthesized chalcone derivatives and these two drugs. Methods Determination of the potent antiviral activity of newly synthesized chalcone derivatives against SARS-CoV-2 by calculating the RT-PCR cycling threshold (C-t) values. Results Antiviral activities of the compounds varied because of being dose dependent. Compound 6, 7, 9, and 16 were highly effective against SARS-CoV-2 at the concentration of 1.60 mu g/mL. Structure-based virtual screening was carried out against the most important druggable SARS-CoV-2 targets, viral RNA-dependent RNA polymerase, to identify putative inhibitors that could facilitate the development of potential anti-coronavirus disease-2019 drug candidates. Conclusions Computational analyses identified eight compounds inhibiting each target, with binding affinity scores ranging from -4.370 to -2.748 kcal/mol along with their toxicological, ADME, and drug-like properties.

Automated summary

The study compared the anti-SARS CoV-2 activities of newly synthesized chalcone derivatives and two drugs, finding that certain compounds were highly effective against SARS-CoV-2 at specific concentrations. Computational analyses identified potential inhibitors targeting SARS-CoV-2, assisting in the development of potential anti-coronavirus disease-2019 drug candidates.