New Chalcone Derivatives as Effective Anti-SARS-CoV-2 Agents.

Duran, Nizami; Polat, M Fatih; Aktas, Derya Anil; Alagoz, M Abdullah; Ay, Emrah; Cimen, Funda; Tek, Erhan; Anil, Baris; Burmaoglu, Serdar; Algul, Oztekin

AIMS Flavonoids and related compounds, such as quercetin-based antiviral drug Gene-Eden-VIR/Novirin, inhibit the protease of severe acute respiratory syndrome coronavirus (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 The current study aimed to determine the potent antiviral activity of newly synthesized chalcone derivatives against SARS-CoV-2 by calculating the RT-PCR cycling threshold (Ct) values. RESULTS Antiviral activities of the compounds varied due to being dose dependent. Compound 6, 7, 9 and 16 were highly effective against SARS-CoV-2 at concentrations of 1.60 µg/mL. Structure-based virtual screening was carried out against the most important druggable SARS-CoV-2 targets, viral RNA-dependent RNA polymerase (RdRp), to identify putative inhibitors that could facilitate the development of potential anti-COVID-19 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.