Predictive medicinal metabolites from Momordica dioica against comorbidity related proteins of SARS-CoV-2 infections.

Momordica dioica have proven medicinal potential of antidiabetic, antiviral and immune stimulating properties. Flavonoids and triterpenoids from M. dioica were more extensively investigated for antiviral, antidiabetic and immunomodulatory activities. In this present study, we have predicted the reported bioactive flavonoids and triterpenoids of the plant against the SARS-CoV-2 main protease, RNA-dependent RNA polymerase (RdRp), spike protein, angiotensin converting enzyme (ACE-2) receptor and dipeptidyl peptidase (DPP4) receptor through molecular docking and in silico ADME predictions methods. According to the binding affinities, the two triterpenoids, hederagenin and oleanolic acid exhibited the best docking scores with these proteins than the catechin and quercetin with compared to standard remdesivir, favipiravir and hydroxychloroquine. The in vitro protein-drug studies have also showed significant interaction of catechin and quercetin compounds than standard drugs. The in silico binding studies correlated with the in silico binding studies. Further, M. dioica being used as antidiabetic and its metabolite had significant interaction with DDP4, a comorbidity protein involved in aiding the viral entry. Out of all the natural ligands, quercetin was reported relatively good and safe for humans with high gastrointestinal tract permeability and poor blood brain barrier crossing abilities. Hence, M. dioica phytocompounds reflects promising therapeutic properties against SARS-CoV-2 infections under comorbid conditions such as diabetes, cardiovascular disease and kidney disorders.Communicated by Ramaswamy H. Sarma.