Phytochemicals of Cocculus hirsutus deciphered SARS-CoV-2 inhibition by targeting main proteases in molecular docking, simulation, and pharmacological analyses

Abstract

The COVID-19 pandemic is spreading rapidly due to the outbreak of novel coronavirus SARS-CoV-2 across the globe. Anti-COVID-19 drugs are urgently required in this situation. In this regard, the discovery of promising new anti-COVID-19 moieties is expected from traditional medicine. The study is aimed to discover phytochemicals of Cocculus hirsutus having anti-COVID-19 activity via inhibiting main proteases of SARS-CoV-2. Main proteases (M^pro) of SARS-CoV-2 serve as a protuberant target for anti-COVID-19 drug discovery because it is a key enzyme of coronaviruses and has a pivotal role in mediating viral replication and transcription that makes it an attractive drug target. Recent studies indicated the utility of C. hirsutus in the treatment of viral disorders like Dengue. Phytochemicals from C. hirsutus were docked against SARS-CoV-2 main proteases (6LU7, 5R7Y, 5R7Z, 5R80, 5R81, 5R82) using the PyRx virtual screen tool and discovery studio visualizer. Further, molecular dynamics simulations were performed (for 100 ns) to see conformational stability for all complexes. Pharmacokinetic properties and drug-likeness prediction of selected C. hirsutus phytoconstituents were also performed. Betulin, coclaurine, and quinic acid of C. hirsutus were found promising with significant binding affinity to SARS-CoV-2 M^pro in comparison to control. They have shown stable interactions with the amino acid residues present on the active site of most of the SARS-CoV-2 M^pro and were found as promising anti-COVID-19 candidates. These compounds could be potential leads for the development of target-specific anti-COVID-19 therapeutics while ethnomedicinal uses of this herb could further needed for its detailed antiviral therapeutic exploration.

Communicated by Ramaswamy H. Sarma

Keywords:

• SARS-CoV-2
• Main proteases
• Cocculus hirsutus
• Phytochemicals
• MD simulation
• lead Anti-COVID-19 agent

Acknowledgment

We sincerely acknowledge all the institutions involved in this study.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Funding

The author(s) reported there is no funding associated with the work featured in this article.

Authors’ contributions

MR: Design, Experiment, writing draft manuscript; SP: Experiment, writing draft manuscript JSP: Experiment, writing draft manuscript; NSC: Analysis and draft writing; PG: Conceptualization, Design, Analysis, Draft writing; AK: Conceptualization, Design, Analysis, Finalizing manuscript.