Pharmacoinformatics and hypothetical studies on allicin, curcumin, and gingerol as potential candidates against COVID-19-associated proteases

Abstract

Medicinal plants have been known to provide the essential raw material for the majority of antiviral drugs. This study demonstrated the putative inhibitory potential of curcumin, allicin, and gingerol towards cathepsin K, COVID-19 main protease, and SARS-CoV 3 C-like protease. The pharmacokinetic properties were predicted through the SwissADME server while the corresponding binding affinity of the selected phytocompounds towards the proteins was computed using PyRx-Python Prescription 0.8 and the binding free energy were computed based on conventional molecular dynamics using LARMD server. The ADMET properties revealed all the drugs possess drug-like properties. Curcumin has the highest binding affinities with all the selected proteases while allicin has the lowest binding affinities towards the proteases. Moreover, it was observed that curcumin exhibited the highest binding free energy of À17.90 ± 0.23, À18.21 ± 0.25, and À9.67 ± 0.08 kcal/mol for Cathepsin K, COVID-19 main protease, and SARS-CoV 3 C-like protease, respectively. Based on the activities of the phytocompounds against coronavirus target proteases involved in the viral entry as evident from the results, the study, therefore, suggests that these phytocompounds could be valuable for the development of drugs useful for the prevention of coronavirus entry and replication.

COVID-19, cytokines, inflammation, and spices: How are they related?

“…It reported that quercetrin exhibited inhibition against SARS-CoV-2 Mpro in silico [ 183 ]. Curcumin also demonstrated a high binding free energy for the enzymes Cat K, COVID-19 Mpro, and SARS-CoV 3 C-like protease [ 184 ].…”

Repurposing potential of Ayurvedic medicinal plants derived active principles against SARS-CoV-2 associated target proteins revealed by molecular docking, molecular dynamics and MM-PBSA studies

“…Previously, curcumin has been shown to hinder the replication of SARS-coronavirus as well [128] and identified as a constructive inhibitor of protease. There are ample experimental research findings that support the efficiency of curcumin, gingerol and quercetin against the human viruses including SARS-CoV-2 pathogenesis [84] , [85] , [129] . Gingerol and curcumin extract demonstrated 45% and 40% of protease inhibition at 0.2 mg/mL concentration in an in vitro protease inhibitory assay and the result was further corroborated by pharmacokinetic properties [129] .…”

“…There are ample experimental research findings that support the efficiency of curcumin, gingerol and quercetin against the human viruses including SARS-CoV-2 pathogenesis [84] , [85] , [129] . Gingerol and curcumin extract demonstrated 45% and 40% of protease inhibition at 0.2 mg/mL concentration in an in vitro protease inhibitory assay and the result was further corroborated by pharmacokinetic properties [129] . SARS-CoV-2 genomic resemblance with SARS-coronavirus (>80%) and Middle East Respiratory Syndrome-coronavirus (50%) collectively suggests the possibility of curcumin efficacy against COVID-19 [130] .…”

“…Synergistic antiviral effects of quercetin and ascorbic acid have been effective in preventing viral entry and replication [136] . Experimental and computational evidence augment the efficacy of curcumin, gingerol and quercetin as anti-protease activity [86] , [87] , [88] , [129] . The present study demonstrated the repurposing possibilities of curcumin, gingerol and quercetin based on their binding ability with multiple COVID-19 targets.…”

In Silico Studies of the Biomolecular Interactions Between Natural Products and SARS-CoV-2 Main Protease

“…To accelerate the search for molecules with therapeutic potential, many research groups around the world are using techniques like molecular docking in virtual screening (VS) assays from compounds libraries to identify molecules which are most likely to bind to a drug target, and complementing with molecular dynamics simulations (MDS) to analyze the conformational dynamics of proteins under conditions that mimic biological systems (Lin et al, 2020). With this objective, these tools were used to evaluate the inhibitory potential of natural products (NPs) (C et al, 2020;Ibrahim et al, 2020;Majumder & Mandal, 2020;Mazzini et al, 2020;Oso et al, 2020;Rao et al, 2020;Sayed et al, 2020;Sen et al, 2020), approved drugs (Gurung et al, 2020;Jiménez-Alberto et al, 2020;Kandeel & Al-Nazawi, 2020) and both of them (Fischer et al, 2020;Gentile et al, 2020;Kanhed et al, 2020) against M pro . The results of these projects show compounds that could be used for in vitro tests to verify their antiviral activity or optimize their structures to improve their affinity for the enzyme.…”