Predicting anti-COVID-19 potential: in silico analysis of Mauritine compound from Ziziphus-spina christi as a promising papain-like protease (PLpro) inhibitor

Abstract

The COVID-19 pandemic caused by the SARS-CoV-2 virus, recognized by the World Health Organization (WHO), has led to 164,523,894 confirmed cases and 3,412,032 deaths globally as of May 20, 2021. SARS-CoV-2 encodes crucial proteases for its replication cycle, including the papain-like protease (PLpro), presenting a potential target for developing COVID-19 treatments. Mauritine, a cyclopeptide alkaloid found in the Ziziphus-spina christi plant, exhibits antiviral properties and was investigated for its affinity and toxicity towards PLpro using molecular docking through MGLTools 1.5.6 with Autodock Tools 4.2. Preceding this, toxicity and ADME prediction were performed via Toxtree 3.1.0 software and SwissADME servers. Results from molecular docking revealed free binding energy values of −8.58; −7.73; −8.36; −6.07; −6.67; −7.83; −7.67; −7.40; and −6.87 Kcal/mol for Mauritine-A, Mauritine-B, Mauritine-C, Mauritine-D, Mauritine-F, Mauritine-H, Mauritine-J, Mauritine-L, and Mauritine-M, respectively. Correspondingly, inhibition constants were 0.51724; 2.14; 0.7398; 35.43; 12.95; 1.83; 2.38; 3.80; and 9.17 µM, respectively. Interactions observed included hydrogen bonds, hydrophobic interactions, and electrostatic interactions between the Mauritine compounds and the receptor. Mauritine-A and Mauritine-C emerged as a promising anti-COVID-19 candidate due to its superior affinity compared to other derivatives, as indicated by research findings. Interestingly, Mauritine-A and Mauritine-C exhibits notable stability as depicted by the RMSD and RMSF graphs, along with a considerable MM-PBSA binding free energy value of −162.431 and −137.500 kJ/mol, respectively.

Communicated by Ramaswamy H. Sarma

Keywords:

• In silico approach
• papain-like protease (PLpro)
• COVID-19
• Mauritine
• Ziziphus-spina christi

Acknowledgment

The author extends gratitude to the Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Islam Bandung, for their financial support granted through the 2020 Independent Research program under No. 03/PEN-PKM/I/2021.

Disclosure statement

The authors declare no conflict of interest.

Author contributions

Conceptualization, T.M.F., F.D., and D.S.F.R.; methodology, T.M.F., D.S.F.R., and T.A.Y.; software, T.M.F., D.S.F.R., A.F.H., A.D.R., and T.A.Y.; validation, R.A., and S.P.; formal analysis, R.A., and S.P.; investigation, R.A., and S.P.; resources, R.A., and S.P.; data curation, R.A., and S.P.; writing—original-draft preparation, R.A., and S.P.; writing—review and editing, T.M.F., F.D., D.S.F.R., A.F.H., A.D.R., and T.A.Y.; visualization, R.A., and S.P.; supervision, T.M.F., F.D., D.S.F.R., and T.A.Y.; All authors have read and agreed to the published version of the manuscript.

Additional information

Funding

This research received no external funding.