ABSTRACT
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in severe damage to the respiratory system. With no specific treatment to date, it is crucial to identify potent inhibitors of SARS-CoV-2 Chymotrypsin-like protease (3CLpro) that could also modulate the enzymes involved in the respiratory damage that accompanies SARS-CoV-2 infection. Here, flavones isolated from Scutellaria baicalensis (baicalein, baicalin, wogonin, norwogonin, and oroxylin A) were studied as possible compounds in the treatment of SARS-CoV-2 and SARS-CoV-2-induced acute lung injuries. Methods: We used structural bioinformatics and cheminformatics to (i) identify the critical molecular features of flavones for their binding activity at human and SARS-CoV-2 enzymes;(ii) predict their drug-likeness and leader-likeness features;(iii) calculate their pharmacokinetic profile, with an emphasis on toxicology;(iv) predict their pharmacodynamic profiles, with the identification of their human body targets involved in the respiratory system injuries;and (v) dock the ligands to SARS-CoV-2 3CLpro. Results: All flavones presented appropriate drug-like and kinetics features, except for baicalin. Flavones could bind to SARS-CoV-2 3CLpro at a similar site, but interact slightly differently with the protease. Flavones’pharmacodynamic profiles predict that (i) wogonin strongly binds at the cyclooxygenase2 and nitric oxide synthase;(ii) baicalein and norwogonin could modulate lysine-specific demethylase 4D-like and arachidonate 15-lipoxygenase;and (iii) baicalein, wogonin, norwogonin, and oroxylin A bind to SARS-CoV-2 3CLpro. Conclusions: Our results propose these flavones as possible potent drugs against respiratory damage that occurs during SARS-CoV-2 infections, with a strong recommendation for baicalein.