Evaluation of potency of the selected bioactive molecules from Indian medicinal plants with MPro of SARS-CoV-2 through in silico analysis

Abstract

Background The recent outbreak of novel SARs CoVid-2 across the globe and absence of specific drug against this virus lead the scientific community to look into some alternative indigenous treatments. India as a hub of ayurvedic and medicinal plants can shed light on its treatment using specific active bio-molecules from these plants. Objectives Keeping our herbal resources in mind we were interested to inquire whether some phytochemicals from Indian spices and medicinal plants can be used as alternative therapeutic agents in contrast to synthetic drugs. Materials and methods We used in-silico molecular docking approach to test whether bioactive molecules of herbal origin such as Hyperoside, Nimbaflavone, Ursolic acid, 6-gingerol, 6-shogaol& 6-paradol, Curcumin, Catechins&Epigallocatechin, α-Hederin, Piperine could bind and potentially block theM pro enzyme of Sars-CoV-2 virus. Results Ursolic acid showed the highest docking score (-8.7 kcal/mol) followed by Hyperoside (-8.6kcal/mol), α-Hederin (-8.5 kcal/mol) and Nimbaflavone (-8.0kcal/mol). Epigallocatechin, Catechins, and Curcumin also exhibited high binding affinity (Docking score -7.3, -7.1 and -7.1 kcal/mol) with the M pro . Rest of the tested phytochemicals exhibited moderate binding and inhibitory effects. Conclusion This finding provides a basis for biochemical assay on Sars-CoV-2 virus.

Inhibition of the main protease of SARS-CoV-2 (Mpro) by repurposing/designing drug-like substances and utilizing nature’s toolbox of bioactive compounds

“…Ursolic acid in particular has also been included in several virtual screening studies, often as a constituent of Ocimum sanctum , with binding energies ranging from -8.88 to -8.52 kcal/mol, as provided by Autodock Vina and Autodock 4.2. Binding of the molecule is attributed to the conventional active site of the protease in two studies, designating hydrogen bonds with residues Thr24, Leu141 and Ser144 [129] , [130] . Another study mentiones formation of hydrogen bonds with residues Arg131, Lys137, Asp197, Thr198, Thr199, Tyr237, Asn238, Tyr239, Leu272, Gln273, Gly275, Met276, Leu286 and Leu287, suggesting binding of ursolic to another site [131] .…”

Natural substances and coronavirus: review and potential for the inhibition of SARS-CoV-2

“…Recently numerous researches have shown its potential inhibitory power against SARS-CoV-2 Mpro both in silico and in vitro (A. Halder et al, 2021). In an in vitro study with curcumin and its analogues, the order of inhibitory effects was bisdemethoxycurcumin < curcumin < dimethylcurcumin.…”

“…Curcumin has a variety of antiviral activities against dengue virus, herpes simplex virus, Zika virus and chikungunya virus. CC also inhibits aminopeptidase N (APN) which has been identified as a cellular receptor for alpha CoV (L. Chen et al, 2020;Halder et al, 2021).…”

Bioactive Compounds from the Zingiberaceae Family with Known Antioxidant Activities for Possible Therapeutic Uses

“…CUR was found to bind potently to angiotensin-converting enzyme 2 (ACE2), mutated spikes, and mutated spike–ACE2 complexes, possibly restricting viral entry [ 143 ]. CUR, 6-gingerol, 6-shogaol, and 6-paradol exhibited moderate binding affinity to and demonstrated moderate inhibition of the M-pro enzyme of the SARS-CoV-2 virus [ 144 ]. CUR and 6-gingerol were also found to putatively inhibit cathepsin K, SARS-CoV-2’s main protease, and SARS-CoV 3-C-like protease [ 145 ].…”