Design and in silico investigation of novel Maraviroc analogues as dual inhibition of CCR-5/SARS-CoV-2 M^pro

Abstract

A sudden increase in life-threatening COVID-19 infections around the world inflicts global crisis and emotional trauma. In current study two druggable targets, namely SARS-COV-2 M^pro and CCR-5 were selected due to their significant nature in the viral life cycle and cytokine molecular storm respectively. The systematic drug repurposing strategy has been utilized to recognize inhibitory mechanism through extensive in silico investigation of novel Maraviroc analogues as promising inhibitors against SARS-CoV-2 M^pro and CCR-5. The dual inhibition specificity approach implemented in present study using molecular docking, molecular dynamics (MD), principal component analysis (PCA), free energy landscape (FEL) and MM/PBSA binding energy studies. The proposed Maraviroc analogues obtained from in silico investigation could be easily synthesized and constructive in developing significant drug against COVID-19 pandemic, with essentiality of their in vivo/in vitro evaluation to affirm the conclusions of this study. This will further fortify the concept of single drug targeting dual inhibition mechanism for treatment of COVID-19 infection and complications.

Graphical Abstract

Communicated by Ramaswamy H. Sarma

Keywords:

• Maraviroc
• CCR-5 antagonist
• SARS-CoV-2 M^pro inhibitor
• anti HIV
• COVID-19
• molecular docking
• molecular dynamics (MD) simulation

Acknowledgements

Authors are thankful to V-life Sciences for providing software & Department of Organic Chemistry, Andhra University. Authors are also thankful to Institute of research and consulting studies at King Khalid University for funding this research through grant number 3-N-20/21.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Authors are thankful to V-life Sciences for providing software & Department of Organic Chemistry, Andhra University. Authors are also thankful to Institute of research and consulting studies at King Khalid University for funding this research through grant number 3-N-20/21.