Bacterial protein azurin and derived peptides as potential anti-SARS-CoV-2 agents: insights from molecular docking and molecular dynamics simulations

Abstract

The current pandemic SARS-CoV-2 has wreaked havoc in the world, and neither drugs nor vaccine is available for the treatment of this disease. Thus, there is an immediate need for novel therapeutics that can combat this deadly infection. In this study, we report the therapeutic assessment of azurin and its peptides: p18 and p28 against the viral structural S-protein and non-structural 3CL^pro and PL^pro proteins. Among the analyzed complexes, azurin docked relatively well with the S2 domain of S-protein compared to the other viral proteins. The derived peptide p18 bound to the active site domain of the PL^pro protein; however, in other complexes, lesser interactions were recorded. The second azurin derived peptide p28, fared the best among the docked proteins. p28 interacted with all the three viral proteins and the host ACE-2 receptor by forming several electrostatic and hydrogen bonds with the S-protein, 3CL^pro, and PL^pro. MD simulations indicated that p28 exhibited a strong affinity to S-protein and ACE-2 receptor, indicating a possibility of p28 as a protein-protein interaction inhibitor. Our data suggest that the p28 has potential as an anti-SARS-CoV-2 agent and can be further exploited to establish its validity in the treatment of current and future SARS-CoV crisis.

Communicated by Ramaswamy H. Sarma

Keywords:

• SARS-CoV-2
• azurin
• p28
• coronavirus
• molecular dynamic simulation

Acknowledgements

The author SS acknowledges research fellowship from NIT Warangal. CS and SKS thankfully acknowledge RUSA-Phase 2.0 Policy (TNmulti-Gen), Dept. of Edn, Govt. of India (Grant No: F.24-51/2014-U).

Disclosure statement

No potential conflict of interest is reported by the authors.

Author contribution

Santanu Sasidharan: Methodology, Software, Validation and Writing-initial draft preparation. Chandrabose Selvaraj: Software, Validation, Writing-Reviewing and Editing; Sanjeev Kumar Singh: Software, Visualization, Validation, Writing-Reviewing and Editing; Vikash Kumar Dubey: Software, Writing-Reviewing and Editing; Sachin Kumar: Conceptualization, Writing-Reviewing and Editing; Arsénio M Fialho: Conceptualization, Resources, Writing-Reviewing and Editing; Prakash Saudagar: Conceptualization, Visualization, Validation, Supervision, Project administration, Writing-Reviewing, and Editing. All authors contributed their inputs in the writing of the draft.