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

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.

Glycyrrhizin and boswellic acids, the golden nutraceuticals: multitargeting for treatment of mild–moderate COVID-19 and prevention of post-COVID cognitive impairment

“…Recently, the activity of BAs, GR and several natural compounds was determined by studying molecular docking to measure the binding of these compounds to the SARS-CoV-2 E protein. BAs and GR were found to have strong antiviral activities against enveloped viruses because they are inhibitors of the SARS-CoV-2 E protein (Fatima et al 2022 ). Data from other bioinformatics studies suggested that BAs possess antiviral properties because BAs target SARS-CoV-2 viruses at an atomic scale on three functional proteins, which are responsible for human cell adhesion (spikes of the virus) or viral RNA replication (main proteins of SARS-CoV-2, Mpro) (Caliebe et al 2021 ; Kadhim et al 2021 ; Roy and Menon 2022).…”

Identification of new pharmacophore against SARS-CoV-2 spike protein by multi-fold computational and biochemical techniques

“…Acetyl 11-keto-β-boswellic acid has been recognized as a potential natural product for the treatment of various viral illnesses 26 , 92 . Boswellia plays a crucial role in various diseases, for instance, its serrata gum resin is already reported in inflammation, chikungunya, and vesicular stomatitis and β-boswellic acids are also reported against HSV-1, HIV, and herpes virus 93 – 96 . In the recent COVID-19 pandemic, boswellic acids with glycyrrhizin (GR) combination displayed successful actions against COVID-19 97 , 98 .…”

SARS-CoV-2 E protein: Pathogenesis and potential therapeutic development

“…Fatima et al [70] The results show that glycyrrhizic acid interacts with E protein at Arg61, Phe23, Tyr57 and Val25, and so does β-boswellic acid with E protein at Leu34, Leu37, Arg38 and Leu39, thus resulting in the structural destruction of E protein. Glycyrrhizic acid and β-boswellic acid show their strong affinity with E protein in the screened compounds.…”