Molecular docking and simulation studies of natural compounds of Vitex negundo L. against papain-like protease (PL^pro) of SARS CoV-2 (coronavirus) to conquer the pandemic situation in the world

Abstract

The severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) is β-coronavirus that is responsible for the pandemic coronavirus disease 2019 (COVID-19) all over the world. The rapid spread of the novel SARS CoV-2 worldwide is raising a significant global public health issue with nearly 61.86 million people infected and 1.4 million deaths. To date, no specific drugs are available for the treatment of COVID-19. The inhibition of proteases essential for the proteolytic treatment of viral polyproteins is a conventional therapeutic strategy for conquering viral infections. In the study, molecular docking approach was used to screen potential drug compounds among the phytochemicals of Vitex negundo L. against COVID-19 infection. Molecular docking analysis showed that oleanolic acid forms a stable complex and other phyto-compounds ursolic acid, 3β-acetoxyolean-12-en-27-oic acid and isovitexin of V. negundo natural compounds form a less-stable complex. When compared with the control the synergistic interaction of these compounds shows inhibitory activity against papain-like protease (PL^pro) of SARS CoV-2 (COVID-19). The molecular dynamics (MD) simulation (50 ns) were performed on the complexes of PL^pro and the phyto-compounds viz. oleanolic acid, ursolic acid, 3β-acetoxyolean-12-en-27-oic acid and isovitexin followed by the binding free energy calculations using MM-GBSA and these molecules have stable interactions with PL^pro protein binding site. The MD simulation study provides more insight into the functional properties of the protein-ligand complex and suggests that these molecules can be considered as a potential drug molecule against COVID-19. In this pandemic situation, these herbal compounds provide a rich resource to produce new antivirals against COVID-19.

Communicated by Ramaswamy H. Sarma

Graphical Abstract

(V. negundo plant photo: B. Mahakur, Department of Botany and Biotechnology garden, Ravenshaw University, India)

Keywords:

• Vitex negundo
• compounds
• molecular dynamics
• PL^pro
• SARS CoV-2

Acknowledgements

The authors are thankful to Raiganj University, Graphic Era (Deemed to be University), Ravenshaw University, NGF College of Engineering and Technology, Gautam Buddha University, Proteininsights, ICAR – National Rice Research Institute and Gauhati University for the support. The first author (D. Mitra) are grateful to Government of West Bengal, India for Swami Vivekananda Merit Cum Means Ph.D. Scholarship (WBP191584588825). The authors are grateful to Prof. Ramaswamy H. Sarma, Editor-in-Chief, JBSD; Prof. Vsevolod Makeev, Associate Editor, JBSD and reviewers for their valuable suggestions to increase the scientific quality of the manuscript.

Disclosure statement

The authors declare that there is no conflict of interest.

Additional information

Funding

BM and DPB are grateful to the Department of Science & Technology (DST), Govt. of Odisha, India and giving grants (DST-MRP/RU/BOT/04, DST-MRP Project) for this research work.