Structure-based drug designing for potential antiviral activity of selected natural products from Ayurveda against SARS-CoV-2 spike glycoprotein and its cellular receptor.

Maurya, Vimal K.Kumar, SwatantraPrasad, Anil K.Bhatt, Madan L. B.Saxena, Shailendra K.

10.1007/s13337-020-00598-8

Research curated

Abstract

The recent outbreak of COVID-19 caused by SARS-CoV-2 brought a great global public health and economic concern. SARS-CoV-2 is an enveloped RNA virus, from the genus Betacoronavirus. Although few molecules have been tested and shown some efficacy against SARS-CoV-2 in humans but a safe and cost-effective attachment inhibitors are still required for the treatment of COVID-19. Natural products are gaining attention because of the large therapeutic window and potent antiviral, immunomodulatory, anti-inflammatory, and antioxidant properties. Therefore, this study was planned to screen natural products from Ayurveda that have the potential to modulate host immune system as well as block the virus entry in host cells by interfering its interaction with cellular receptor and may be used to develop an effective and broad-spectrum strategy for the management of COVID-19 as well as other coronavirus infections in coming future. To decipher the antiviral activity of the selected natural products, molecular docking was performed. Further, the drug-likeness, pharmacokinetics and toxicity parameters of the selected natural products were determined. Docking results suggest that curcumin and nimbin exhibits highest interaction with spike glycoprotein (MolDock score − 141.36 and − 148.621 kcal/mole) and ACE2 receptor (MolDock score − 142.647 and − 140.108 kcal/mole) as compared with other selected natural products/drugs and controls. Also, the pharmacokinetics data illustrated that all selected natural products have better pharmacological properties (low molecular weight; no violation of Lipinski rule of five, good absorption profiles, oral bioavailability, good blood–brain barrier penetration, and low toxicity risk). Our study exhibited that curcumin, nimbin, withaferin A, piperine, mangiferin, thebaine, berberine, and andrographolide have significant binding affinity towards spike glycoprotein of SARS-CoV-2 and ACE2 receptor and may be useful as a therapeutic and/or prophylactic agent for restricting viral attachment to the host cells. However, few other natural products like resveratrol, quercetin, luteolin, naringenin, zingiberene, and gallic acid has the significant binding affinity towards ACE2 receptor only and therefore may be used for ACE2-mediated attachment inhibition of SARS-CoV-2.

Source: PMC

Related molecules

Name	Synonyms	Genes
Curcumin
Nimbin
Withaferin
Piperine
mangiferin
Thebaine
Berberine
Andrographolide
Spike glycoprotein	Spike protein, S glycoprotein, S-Protein, S1, S2, S3, Peplomer protein, E2	S, ORF2
Angiotensin-converting enzyme 2	ACE-related carboxypeptidase, ACE2	ACE2
Angiotensin-converting enzyme 2-Spike glycoprotein interface

Related interactions

Target	Drug	Type	Result
Spike glycoprotein	Curcumin	Computational	positive
Angiotensin-converting enzyme 2	Curcumin	Computational	positive
Spike glycoprotein	Nimbin	Computational	positive
Angiotensin-converting enzyme 2	Nimbin	Computational	positive
Spike glycoprotein	Withaferin	Computational	positive
Angiotensin-converting enzyme 2-Spike glycoprotein interface	Withaferin	Computational	positive
Angiotensin-converting enzyme 2-Spike glycoprotein interface	Piperine	Computational	positive
Angiotensin-converting enzyme 2-Spike glycoprotein interface	mangiferin	Computational	positive
Angiotensin-converting enzyme 2-Spike glycoprotein interface	Thebaine	Computational	positive
Angiotensin-converting enzyme 2-Spike glycoprotein interface	Berberine	Computational	positive
Angiotensin-converting enzyme 2-Spike glycoprotein interface	Andrographolide	Computational	positive