Natural derivatives with dual binding potential against SARS-CoV-2 main protease and human ACE2 possess low oral bioavailability: a brief computational analysis

The world is witnessing severe health meltdown due to COVID-19. Generic antiviral drug remdesivir has been found to reduce time to clinical recovery but with insignificant clinical benefits and the antimalarial drug, hydroxychloroquine has been red flagged by USFDA for use as a prophylactic measure due to its cardiotoxicity. There is an acute requirement for a drug candidate that has significant clinical benefit with minimal to no side effects. With restricted access to wet laboratory techniques, an alternative approach is to engage in computational screening of lead molecules that could inhibit SARS-CoV-2 at different stages of its infectious cycle. Severalin silicostudies on natural derivatives, especially that present in daily refreshments (tea and fruit juices), staple food (black rice, red onions, soy beans etc) and traditional medicines (extracts of herbs, leaves and flowers) have been identified as potential drug candidates that bind efficiently with the key viral proteins. However, oral bioavailability of these nutriments is considerably low due to either poor permeability or loss of structure and function due to digestion in the gastrointestinal tract. Here we discuss few natural secondary metabolites (Delphinidin 3,5-diglucoside, Scutellarein 7-glucoside, Avicularin and 3,5-Di-O-galloylshikimic acid) that showed encouraging binding affinity against coronavirus main protease (M-pro) and human ACE2 receptor with MM-GBSA energies up to -74.0 Kcal/mol and -79.5 Kcal/mol, respectively. However, their Abbott bioavailability score (ABS) of 0.11 or 0.17 predicts poor oral bioavailability. This study could trigger interest to engineer potential natural products in managing present or future pandemics. Communicated by Ramaswamy H. Sarma

Automated summary

The world is in the midst of a health crisis due to COVID-19, prompting the search for a drug candidate with significant clinical benefits and minimal side effects. Computational screening of molecules that can inhibit SARS-CoV-2 at different stages of its infectious cycle is being explored as an alternative approach.