Natural compounds fromClerodendrumspp. as possible therapeutic candidates against SARS-CoV-2: Anin silicoinvestigation

Abstract

The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has rattled global public health, with researchers struggling to find specific therapeutic solutions. In this context, the present study employed an in silico approach to assess the inhibitory potential of the phytochemicals obtained from GC-MS analysis of twelve Clerodendrum species against the imperative spike protein, main protease enzyme M pro and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2. An extensive molecular docking investigation of the phytocompounds at the active binding pockets of the viral proteins revealed promising inhibitory potential of the phytochemicals taraxerol, friedelin and stigmasterol. Decent physicochemical attributes of the compounds in accordance with Lipinski's rule of five and Veber's rule further established them as potential therapeutic candidates against SARS-CoV-2. Molecular mechanics-generalized Born surface area (MM-GBSA) binding free energy estimation revealed that taraxerol was the most promising candidate displaying the highest binding efficacy with all the concerned SARS-CoV-2 proteins included in the present analysis. Our observations were supported by robust molecular dynamics simulations of the complexes of the viral proteins with taraxerol for a timescale of 40 nanoseconds. It was striking to note that taraxerol exhibited better binding energy scores with the concerned viral proteins than the drugs that are specifically targeted against them. The present results promise to provide new avenues to further evaluate the potential of the phytocompound taraxerol in vitro and in vivo towards its successful deployment as a SARS-CoV-2 inhibitor and combat the catastrophic COVID-19.

Anisotine and amarogentin as promising inhibitory candidates against SARS-CoV-2 proteins: a computational investigation

“…The compounds anisotine (1.90 lM), adhatodine (7.35 lM), beta-carotene (5.24 lM), eugenol (4.42 lM), mangiferin (3.16 lM) and beta-amyrin (6.21 lM) were predicted to be potent inhibitors and promising lead compounds based on our observations of inhibition constant values (Table 1). Recently, our group (Kar et al, 2020) conducted an interaction profiling of the drug arbidol, that is commonly targeted against SARS-CoV-2 spike protein to inhibit viral attachment with human ACE2 receptor, and reported a binding energy score of À6.2 kcal/mol with the RBD of SARS-CoV-2 spike protein (Kar et al, 2020;Sanders et al, 2020). It was interesting to note that the compounds anisotine, adhatodine, beta-carotene, eugenol, mangiferin and beta-amyrin exhibited significantly higher binding energy scores (p < 0.01) (Table 1) with respect to the drug arbidol.…”

“…Biological diversity has afforded mankind an invaluable source of molecular entities that have, for centuries, been a resource in the production of traditional and formal pharmaceuticals (Kar et al, 2020 ). The process of drug discovery relies heavily upon phytochemicals as remedies to various ailments.…”

Molecular mechanisms of the novel coronavirus SARS-CoV-2 and potential anti-COVID19 pharmacological targets since the outbreak of the pandemic

“…Enisamium was shown to inhibit the activity of the SARS-CoV-2 RNA polymerase and its active metabolite exhibits similar efficacy with remdesivir triphosphate, it is approved in 11 countries and does not require intravenous administration, unlike remdesivir ( Walker et al, 2020 ). In silico approaches have also been used to identify novel inhibitors, either by screening clinically used polymerase inhibitors, or FDA approved drugs and/or natural compounds ( Kar et al, 2020 ; Pokhrel et al, 2020 ; Ruan et al, 2020 ; Zhang et al, 2020b ).…”

Screening of Natural Products Targeting SARS-CoV-2–ACE2 Receptor Interface – A MixMD Based HTVS Pipeline

“…Chen et al screened Thioflexibilolide A (Binding Energy: −9.2 kcal/mol) and Candidine (Binding Energy: −9.0 kcal/mol) as best compounds from 2000 natural compounds (Chen et al, 2020). Kar et al performed docking study with natural compounds from Clerodendrum spp., and reported that Taraxerol ( G bind prime MM-GBSA = −45.19 kcal/mol) as most promising inhibitory candidate against the SARS-CoV-2 spike protein (Kar et al, 2020). All the above reported compounds have shown to interact with amino acids in the ACE2-RBD interface region.…”