Anthraquinones: A Promising Multi-target Therapeutic Scaffold To Treat Covid-19

Abstract

The coronavirus disease 19 (Covid-19) pandemic caused by the SARS-CoV-2 virus has become a humanitarian crisis. Considering the severity of the situation we have performed a virtual screening of anthraquinones derivative drugs and phytochemicals targeting simultaneously multiple essential proteins of SARS-CoV-2 namely Mpro, PLpro, RdRp and the spike. Among the 9 screened anthraquinones derivative drugs, valrubicin, idarubicin, daunorubicin, doxorubicin, epirubicin and diacerein were the most potent inhibitors of SARS-CoV-2 Mpro, PLpro, RdRp and Spike simultaneously. Valrubicin has the best affinity towards the spike protein (-9.5 kcal/mol), RdRp (-8.2 kcal/mol) and PLpro (-7.9 kcal/mol) while idarubicin and doxorubicin were the most effective against Mpro (-8.3 kcal/mol). No toxicity measurements are required for these drugs since they were tested prior to their approval by the FDA. Of the 140 screened phytochemicals anthraquinones were the most potent candidates. Hypericin and rhein were able to bind to the active site of all four targets, while chrysophanol, aloesaponarin II, emodine, aloe-emodine, physcion and danthron simultaneously bound to the active site of SARS-CoV-2 Mpro, Spike and RdRp. Hypericin showed the best affinity towards the spike protein (-9.7 kcal/mol), RdRp (-10.2 kcal/mol) and PLpro (-7.8 kcal/mol), while chrysophanol was the most effective one against Mpro (-8.4 kcal/mol). Our overall prediction findings indicate that anthraquinones may inhibit the activity of the four essential proteins of SARS-CoV-2 and those results can pave the way in drug discovery.