In silico analysis of phytochemicals as potential inhibitors of proteases involved in SARS-CoV-2 infection

Abstract

In silico analysis of six phytochemicals, flabelliferin, marmelosin, piperine, ocimin, curcumin and leucoanthocyanin, along with three drug compounds, nelfinavir, remdesivir and hydroxychloroquine, as positive control against drug targets of one SARS-CoV-2 viral protease, COVID-19 main protease (SARS CoV-2 3CL pro /M pro ), two coronavirus proteases, SARS-CoV main peptidase (SARS CoV M pro ), SARS-CoV main proteinase (SARS CoV 3CL pro ), and one human cellular transmembrane serine proteinase (TMPRSS2), was carried out. Except leucoanthocyanin all other phytochemicals proved better than all three positive control drugs against SARS-CoV main peptidase, whereas, flabelliferin was found to be the potential inhibitor for SARS-CoV main proteinase out performing all the positive control drugs and phytochemicals. Amongst the compounds studied, the best inhibitor for COVID-19 main protease was nelfinavir followed by flabelliferin and ocimin. Flabelliferin was found to the best promising inhibitor of human cellular transmembrane serine proteinase, followed by nelfinavir, curcumin, piperine and marmelosin. The result on the inhibition of human cellular transmembrane serine proteinase against COVID-19 has a stable therapeutic advantage as mutation may quickly occur on viral drug targets. Hence, all the phytochemicals tested in the present study are the potential inhibitors of the all the four drug targets and can form a part of therapeutics against COVID-19 with further clinical studies.

Molecular dynamics and docking studies on potentially active natural phytochemicals for targeting SARS-CoV-2 main protease

“…Moreover, the corresponding binding energies are also found to be greater than 7. [43] reported a binding energy value of -7.2 kcal/mol for Imperatorin-M pro complex (also known as Marmelosin) obtained from autodock which is lower than that obtained from the current study (-8.39 kcal/mol). Aegelinoside B, an alpha glucosidase inhibitor, is the phytochemical that can be extracted from the leaves of Aegle marmelos.…”

In Silico Analysis Using SARS-CoV-2 Main Protease and a Set of Phytocompounds to Accelerate the Development of Therapeutic Components against COVID-19

“…Many phytocompounds have been used in traditional medicine to treat ailments possibly caused by viruses [62][63][64]. Several studies evaluated the pharmacological nature of the phytocompounds and COVID-19 proteins [65][66][67].…”

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

“…Inhibition of protease (chymotrypsin-like protease, 3CLpro or main protease, Mpro) ( Joshi et al, 2020 ; Rudrapal et al, 2020 ; Umadevi et al, 2020 , Sepay et al, 2020 , Chowdhury, 2020 , Gowrishankar et al, 2021 ), and RNA-dependent RNA polymerase (RdRp) polymerase ( Motiwale et al, 2020 , Bhat, 2021 , Naik et al, 2021 , Ishola et al, 2021 , Shree et al, 2020 , Schoeman and Fielding, 2019 ) enzymes has been attributed to be crucial for blocking maturation of viral particles, viral replication and further infection. Several research related to the development of natural products as inhibitors of protease and polymerase enzymes have already been reported using computational modeling and approaches (Prajapat et al, 2020; Motiwale et al, 2020 ; Schoeman and Fieldin, 2019).…”