In silico preliminary evaluation of bioactive compounds from five Unani drugs as potential SARS-CoV-2 inhibitors

Abstract

COVID-19, although on the decline currently with the role of vaccines, still impose public health challenges due to the quick evolution of SARS-CoV-2 into several variants and periodic surge in cases. Identifying therapeutic interventions that can effectively target virulence, boost immune response, and protect target organs is of paramount importance. Behi dana (Cydonia oblonga), Unnab (Zizyphusjujuba), Sapistan (Cordia myxa), Banafsha (Viola odorata), and Aslassus (Glycyrrhiza glabra) are the most commonly prescribed drugs in Unani Medicine for upper respiratory tract infections and have been shown to have antiviral, antimicrobial, immunomodulatory, anti-inflammatory, and antioxidant activities. The current study investigated the inhibitory response of phytocompounds contained in these drugs on putative SARS-CoV-2 drug targets. Phytocompounds structures were retrieved from PubChem database, with some being constructed using Marvin Sketch. 3CLpro and SARS-CoV-2 S glycoprotein were chosen as the target proteins. To determine the binding affinities and predict top-ranking poses with the highest scores, AutoDock Vina was utilized. The results of molecular docking indicated that the phytoconstituents of these drugs interacted well with 3CLpro and S glycoprotein with strong binding affinities. Zijusesquilignan A, Zijusesquilignan B, Emetine, Glycyrrhizin and 3,4-Dicaffeoylquinic acid, Vicenin-2, Isoschaftoside, Schaftoside, Zijusesquilignan A & C, Emetine, Glycyrrhizin were shown to be intriguing candidates with the capability of interacting with spike glycoprotein and 3CLpro, respectively and preventing the virus from replicating and infecting the host. Molecular simulation results showed the structural stability of the docked complexes. To conclude, the combination of these drugs may be useful in the development of novel remedial candidates for COVID-19; however, additional in vitro and in vivo investigations are required to ascertain this claim.