Molecular and structural insights of β-boswellic acid and glycyrrhizic acid as potent SARS-CoV-2 Envelope protein inhibitors

Syeda Warisul Fatima; Shahenvaz Alam; Sunil K Khare

doi:10.1016/j.phyplu.2022.100241

Molecular and structural insights of β-boswellic acid and glycyrrhizic acid as potent SARS-CoV-2 Envelope protein inhibitors

Phytomed Plus. 2022 May;2(2):100241. doi: 10.1016/j.phyplu.2022.100241. Epub 2022 Feb 12.

Authors

Syeda Warisul Fatima¹, Shahenvaz Alam¹, Sunil K Khare¹

Affiliation

¹ Enzyme and Microbial Biochemistry Laboratory,Department of Chemistry,Indian Institute of Technology Delhi, New Delhi 110016, India.

Abstract

Background: Over million people have been infected with SARS-CoV-2 virus worldwide, with around 3% reported deaths till date. A few conventional antiviral treatments have been tried to mitigate the coronavirus. However, many alternative therapeutics are being evaluated worldwide. In the present study, we investigated traditional Indian medicinal compounds antiviral potencies as an effective drug for targeting SARS-CoV-2E. SARS-CoV-2 E protein plays a key role in coronavirus life cycle and is an interesting target for the development of anti-SARS-CoV-2 E drugs.

Methods: Molecular docking studies of medicinal compounds possessing wide range of pharmacological and antiviral activities against enveloped viruses were evaluated with the computer-aided drug design screening software; PyRx. Twelve medicinal compounds isolated from plants were screened and visualized on Biovia Discovery-Studio. Moreover, SARS-CoV-2 E protein's secondary structural insights were deciphered using Swiss Model and ProFunc web server.

Results: Glycyrrhizic acid, triterpene glycoside isolated from plants of Glycyrrhiza (licorice) showed interactions with envelope protein at chain A: Arg 61, chain B: Phe 23, chain B: Tyr 57, and chain C: Val 25. β- boswellic acid, an ayurvedic herb (pentacyclic terpenoid are produced by Boswellia) represented direct interactions and indirect binding with chain C. Their pharmacological aspects and drug-likeness properties were deduced by DruLiTo. Toxicological assessment, along with their ADME profiling, was validated using vNNADMET. The findings showed that ligands, β-boswellic acid, and glycyrrhizic acid possessed the best bindings, with the target having binding affinity (-9.1 kcal/mol) amongst compounds tested against SARS-CoV-2 E. In-vitro studies reveals the promising effect as potent SARS-CoV-2 E inhibitors. Functionality loss and structural disruptions with ∼90% were observed by UV-spectra and fluorescent based analyses.

Conclusion: The study demonstrated that β-boswellic acid, and glycyrrhizic acid are strong SARS-CoV-2 E protein inhibitors. In addition, the work linked GA antiviral activity to its effect on SARS-CoV- 2 E protein that can pave the way for designing antiviral therapeutics.

Keywords: Coronavirus; Envelope protein; Indian medicinal plants; Inhibitors; Molecular docking; SARS-CoV-2 E.