Phytomolecules having flavone and napthofuran nucleus exhibited better binding G-score against protease and SPIKE protein of novel corona virus COVID-19

Rajan, Karthik Aravinda Muthusamy VS Ramanathan M.

The present study aims to screen the different phytoconstituents and drugs for potential treatment of the corona virus COVID-19 and for specificity through virtual screening. The plant molecules selected were based upon traditional knowledge and are prescribed in the Indian system of medicine for infectious/ respiratory conditions. The three target proteins selected for the study are 3CLpro, PLpro, and SPIKE. These proteins have defined pathological roles in disease transmission. The virtual screening was carried out in these proteins using the GLIDE Schrödinger Maestro software version 11.9.011. The efficacy was assessed by the calculated G-score of the ligand interaction with the amino acid side chains of the ligand binding domain. Molecules such as saponarin, mangiferin, and hesperidin exhibited better G-score with 3CLpro and PLpro. Similarly, diphyllin and tuberculatin exhibited better G-score for SPIKE protein. The reference anti malarial drug hydroxychloroquine showed better interactions with 3CLpro and PLpro. Similarly, protease inhibitors and antiviral drugs have shown interaction with 3CLpro specific protease protein. Interestingly, SPIKE protein ligands, diphyllin and tuberculatin from Justicia adhatoda (vasaka), were found to be unique and did not show affinity to protease inhibitor. It can be concluded, that the molecules having flavone scaffolds show better binding affinity with protease proteins 3CLpro and PLpro. SPIKE protein scaffold is different and showed better binding affinity with molecules having naptho-furan ring. The traditionally used plant phytoconstituents did not exhibit good binding affinity;however, we believe that a combination of these herbs might induce human immune system against microbial infection.