Cyanobacterial metabolites as promising drug leads against the M^pro and PL^pro of SARS-CoV-2: an in silico analysis

Abstract

A novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has emerged as the causative agent behind the coronavirus disease 2019 (COVID-19) pandemic. Treatment efforts have been severely impeded due to the lack of specific effective antiviral drugs for the treatment of COVID-associated pathologies. In the present research endeavour the inhibitory prospects of cyanobacterial metabolites were assessed at the active binding pockets of the two vital SARS-CoV-2 proteases namely, main protease (M^pro) and the papain-like protease (PL^pro) that proteolytically process viral polyproteins and facilitate viral replication, employing an in silico molecular interaction-based approach. It was evident from our analysis based on the binding energy scores that the metabolites cylindrospermopsin, deoxycylindrospermopsin, carrageenan, cryptophycin 52, eucapsitrione, tjipanazole, tolyporphin and apratoxin A exhibited promising inhibitory potential against the SARS-CoV-2 M^pro. The compounds cryptophycin 1, cryptophycin 52 and deoxycylindrospermopsin were observed to display encouraging binding energy scores with the PL^pro of SARS-CoV-2. Subsequent estimation of physicochemical properties and potential toxicity of the metabolites followed by robust molecular dynamics simulations and analysis of MM-PBSA energy scoring function established deoxycylindrospermopsin as the most promising inhibitory candidate against both SARS-CoV-2 proteases. Present research findings bestow ample scopes to further exploit the potential of deoxycylindrospermopsin as a successful inhibitor of SARS-CoV-2 in vitro and in vivo and pave the foundation for the development of novel effective therapeutics against COVID-19.

Communicated by Ramaswamy H. Sarma

Keywords:

• SARS-CoV-2
• cyanobacterial metabolites
• molecular docking
• drug-likeness
• molecular dynamics simulations
• MM-PBSA
• deoxycylindrospermopsin

Acknowledgements

AR acknowledges Lovely Professional University, India for providing the necessary infrastructure facility. We also thank the anonymous reviewers for their suggestions which helped to improve the manuscript.

Disclosure statement

The authors wish to declare that there are no conflicts of interest.

Additional information

Funding

The Mangosuthu University of Technology is acknowledged for financial support.