Evaluation of Clove Phytochemicals as Potential Antiviral Drug Candidates Targeting SARS-CoV-2 Main Protease: Computational Docking, Molecular Dynamics Simulation, and Pharmacokinetic Profiling

Arun Chandra Manivannan; Arunkumar Malaisamy; Murugesh Eswaran; Arun Meyyazhagan; Vijaya Anand Arumugam; Kannan R R Rengasamy; Balamuralikrishnan Balasubramanian; Wen-Chao Liu

doi:10.3389/fmolb.2022.918101

Evaluation of Clove Phytochemicals as Potential Antiviral Drug Candidates Targeting SARS-CoV-2 Main Protease: Computational Docking, Molecular Dynamics Simulation, and Pharmacokinetic Profiling

Front Mol Biosci. 2022 Jun 28:9:918101. doi: 10.3389/fmolb.2022.918101. eCollection 2022.

Authors

Arun Chandra Manivannan¹, Arunkumar Malaisamy², Murugesh Eswaran³, Arun Meyyazhagan⁴, Vijaya Anand Arumugam⁵, Kannan R R Rengasamy⁶, Balamuralikrishnan Balasubramanian⁷, Wen-Chao Liu⁸

Affiliations

¹ Department of Microbiology, Alagappa University, Karaikudi, India.
² Integrative Biology Division, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
³ Department of Bioinformatics, Bharathiar University, Coimbatore, India.
⁴ Department of Life Sciences, CHRIST (Deemed to be University), Bengaluru, India.
⁵ Department of Human Genetics and Molecular Biology, Bharathiar University, Coimbatore, India.
⁶ Department of Pharmacology, Centre for Transdisciplinary Research, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, India.
⁷ Department of Food Science and Biotechnology, College of Life Science, Sejong University, Seoul, South Korea.
⁸ Department of Animal Science, College of Coastal Agricultural Sciences, Guangdong Ocean University, Zhanjiang, China.

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus can cause a sudden respiratory disease spreading with a high mortality rate arising with unknown mechanisms. Still, there is no proper treatment available to overcome the disease, which urges the research community and pharmaceutical industries to screen a novel therapeutic intervention to combat the current pandemic. This current study exploits the natural phytochemicals obtained from clove, a traditional natural therapeutic that comprises important bioactive compounds used for targeting the main protease of SARS-CoV-2. As a result, inhibition of viral replication effectively procures by targeting the main protease, which is responsible for the viral replication inside the host. Pharmacokinetic studies were evaluated for the property of drug likeliness. A total of 53 bioactives were subjected to the study, and four among them, namely, eugenie, syzyginin B, eugenol, and casuarictin, showed potential binding properties against the target SARS-CoV-2 main protease. The resultant best bioactive was compared with the commercially available standard drugs. Furthermore, validation of respective compounds with a comprehensive molecular dynamics simulation was performed using Schrödinger software. To further validate the bioactive phytochemicals and delimit the screening process of potential drugs against coronavirus disease 2019, in vitro and in vivo clinical studies are needed to prove their efficacy.

Keywords: SARS-CoV-2; casuarictin; clove; main protease; phytochemicals.