In silico screening of phytopolyphenolics for the identification of bioactive compounds as novel protease inhibitors effective against SARS-CoV-2

Identification of bioactive molecules from Triphala (Ayurvedic herbal formulation) as potential inhibitors of SARS-CoV-2 main protease (Mpro) through computational investigations

“…Tannic acid even inhibits both M pro and TMPRSS2 protease, effectively suppressing SARS-CoV-2 ( Wang et al, 2020 ). The catalytic residues of 3CL pro (or M pro in the case of SARS-CoV-2) are Cys145 and His41, which are surrounded by other residues that confer substrate specificity ( Rudrapal et al, 2021 , Singh et al, 2020 ).…”

“…The crystal structure of the Mpro of SARS-CoV-2 bound with non-covalent inhibitor X77 (N-(4-tert-butylphenyl)-N-[(1R)-2-(cyclohexylamino)-2-oxo-1-(pyridin-3-yl) ethyl]-1H-imidazole-4-carboxamide) at a resolution of 2.1 Å (PDB id: 6W63) ( Rudrapal et al, 2021 ) was retrieved from RCSB Protein data bank (https://www.rcsb.org/). The maestro's protein preparation wizard (version 2021-2 Schrodinger suite) was used to prepare proteins by removing all water within 5Å distance from the ligand, filling amino acid side chains, adding missing hydrogen atoms, creating disulfide bonds, and optimizing hydrogen bonds.…”

“…Papain-like protease (PL pro ) is another enzyme similar to M pro ; it generates Nsp1-Nsp3 by breaking at various sites, thereby generating essential proteins that suppress the immune system by speeding up the infection process in the host cell ( Harcourt et al, 2004 ). One of the important targets is RNA-dependent RNA polymerase (RdRp) as the viral genome depends on it for its replication and transcription ( Borgio et al, 2020 , Rudrapal et al, 2021 ). In literature ( Ahmad et al, 2021 ), the possible potential of Indian medicinal plants and formulations against SARS-CoV-2/ COVID-19 has been mentioned based upon the recommendation ( https://www.ayush.gov.in/docs/ayush-Protocol-covid-19.pdf ; https://www.ayush.gov.in/docs/ayurved-guidlines.pdf) of AYUSH (Ayurveda, Yoga, Naturopathy, Unani, Siddha, Sowa-Rigpa and Homoeopathy).The usefulness of Triphala formulation and other Ayurvedic herbal remedies as therapeutic supplements in COVID-19 has also been reported in some recent literature ( Ozah, 2020 ).…”

Repurposing of phytomedicine-derived bioactive compounds with promising anti-SARS-CoV-2 potential: Molecular docking, MD simulation and drug-likeness/ADMET studies

“…Results of drug-likeness revealed that all these fifteen compounds exhibited acceptable drug-like properties. Lipinski’s rule of five ( Rudrapal et al, 2021 ) and Veber rule ( Zhang and Lazim, 2017 ) were obeyed. Compounds with LogPo/w ≤ 5, Mol.…”

“…The disease has led to a catastrophic situation with unprecedented health and economic burden of current times around the world. Infection with SARS-CoV-2 causes mild illness (fever, cough, sore throat) to severe respiratory disease ( Tijjani et al, 2021 , Kumar et al, 2021b , Rasmi et al, 2021 , Rudrapal et al, 2021 ). This devastating infectious disease may even cause fatal systemic complications and eventually deaths.…”