Screening of plant-based natural compounds as a potential COVID-19 main protease inhibitor: anin silicodocking and molecular dynamics simulation approach

Abstract

A new strain of coronavirus (CoV) has been identified as SARS-CoV-2, which is responsible for the recent COVID-19 pandemic. Currently, there is no approved vaccine or drug available to combat the pandemic. COVID-19 main protease (M pro) is a key CoV enzyme, which plays an important role in triggering viral replication and transcription, turns it into an attractive target. Therefore, we aim to screen natural products library to find out potential COVID-19 M pro inhibitors. Plant-based natural compounds from Sigma-Aldrich plant profiler chemical library have been screened through virtual molecular docking and molecular dynamics simulation to identify potential inhibitors of COVID M pro. Our virtual molecular docking results have shown that there are twenty-eight natural compounds with a greater binding affinity toward the COVID-19 M pro inhibition site as compared to the co-crystal native ligand Inhibitor N3 (-7.9 kcal/mol). Also, molecular dynamics simulation results have confirmed that Peonidin 3-O-glucoside, Kaempferol 3-Ob-rutinoside, 4-(3,4-Dihydroxyphenyl)-7-methoxy-5-[(6-O-b-D-xylopyranosyl-b-D-glucopyranosyl)oxy]-2H-1benzopyran-2-one, Quercetin-3-D-xyloside, and Quercetin 3-O-a-L-arabinopyranoside (selected based on the docking score) possess a significant amount of dynamic properties such as stability, flexibility and binding energy. Our In silco results suggests that all the above mention natural compounds have the potential to be developed as a COVID-19 M pro inhibitor. But before that, it must go through under the proper preclinical and clinical trials for further scientific validation.

Pomegranate Peel Extract as an Inhibitor of SARS-CoV-2 Spike Binding to Human ACE2 Receptor (in vitro): A Promising Source of Novel Antiviral Drugs

“…The activity of plants secondary metabolites against SARS-CoV-2 infection and replication has been extensively reviewed in the last months (da Silva Antonio et al, 2020;Sayed et al, 2020;Weng, 2020) and many studies, based on in silico approaches, suggested some of them as potential drug candidates for COVID-19 treatment (Majumder and Mandal, 2020;Singh et al, 2020). Both viral structural proteins, like Spike, and non-structural proteins, such as 3CLpro, PLpro, and RdRp, have been proposed as valuable targets for anti-SARS-CoV-2 therapeutic strategies.…”

A pomegranate peel extract as inhibitor of SARS-CoV-2 Spike binding to human ACE2 (in vitro): a promising source of novel antiviral drugs

“…The activity of plant secondary metabolites against SARS-CoV-2 infection and replication has been extensively reviewed in the last months 55-58 and many studies, based on in silico approaches, suggested some of them as potential drug candidates for COVID-19 treatment 59 . Both viral structural proteins, like Spike, and non-structural proteins, such as 3CL pro , PL pro and RdRp, have been proposed as valuable targets for anti-SARS-CoV-2 therapeutic strategies.…”

Natural and Nature-Derived Products Targeting Human Coronaviruses

“…Regarding 3CL pro , recent efforts, have identified potential inhibitors among: alkaloids [ 133 , 134 , 135 , 136 , 137 , 138 ], and especially indole alkaloids [ 139 , 140 , 141 , 142 , 143 , 144 ]; terpenoids [ 138 ], and especially diterpenes [ 133 , 145 ]; sesquiterpenes [ 134 , 146 , 147 ], sesquiterpene lactones [ 148 ], and triterpenes [ 133 , 136 , 140 , 149 ]; anthocyanins [ 150 , 151 ] and proanthocyanidins [ 152 , 153 ]; ellagitannins [ 153 , 154 ]; flavonoids [ 133 , 137 , 140 , 144 , 147 , 148 , 152 , 155 , 156 , 157 , 158 , 159 , 160 , 161 ], biflavonoids [ 162 ], and macrocyclic flavonoids [ 148 ]; isoflavones [ 144 , 148 ]; chalcones […”