MD simulation and MM/PBSA identifies phytochemicals as bifunctional inhibitors of SARS-CoV-2

Abstract

The global spread of SARS-CoV-2 has resulted in millions of fatalities worldwide, making it crucial to identify potent antiviral therapeutics to combat this virus. We employed structure-assisted virtual screening to identify phytochemicals that can target the two proteases which are essential for SARS-CoV-2 replication and transcription, the main protease and papain-like protease. Using virtual screening and molecular dynamics, we discovered new phytochemicals with inhibitory activity against the two proteases. Isoginkgetin, kaempferol-3-robinobioside, methyl amentoflavone, bianthraquinone, podocarpusflavone A, and albanin F were shown to have the best affinity and inhibitory potential among the compounds, and can be explored clinically for use as inhibitors of novel coronavirus SARS-CoV-2.

Communicated by Ramaswamy H. Sarma

Keywords:

• Coronavirus
• main protease
• papain-like protease
• phytochemicals
• virtual screening
• MD simulation
• PCA analysis

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

PK & ST would like to acknowledge Science and Engineering Research Board, Department of Science & Technology, Government of India [DST-SERB IPA/2020/000054] and Department of Biotechnology, Government of India [BT/PR40141/BTIS/137/16/2021]. MS and PD thank to MHRD; JKM, thanks to DBT for providing financial assistance; NN thanks to CSIR. Authors would like to pay sincere thanks to Macromolecular Crystallographic Unit (MCU), a Central Facility at Institute Instrumentation Centre (IIC), IIT Roorkee for providing facilities to carry out the computational work.