Screening of natural compounds from Cyperus rotundus Linn against SARS-CoV-2 main protease (Mpro): An integrated computational approach

Coronavirus disease 2019 (COVID-19) is a viral respiratory disease that has been spreading across the globe. The World Health Organization (WHO) declared it as a public health emergency. The treatment of COVID-19 has been hampered due to the lack of effective therapeutic efforts. Main Protease (Mpro) is a key enzyme in the viral replication cycle and its non-specificity to human protease makes it a potential drug target. Cyperus rotundus Linn, which belongs to the Cyperaceae family, is a traditional herbal medicine that has been widely studied for its antiviral properties. In this study, a computational approach was used to screen natural compounds from C. rotundus Linn using BIOVIA Discovery Suite and novel potential molecules against Mpro of SARS-CoV-2 were predicted. Molecular docking was performed using LibDock protocol and selected ligands were further subjected to docking analysis by CDOCKER. The docking scores of the selected ligands were compared with standard antiretroviral drugs such as lopinavir and ritonavir to assess their binding potentials. Interaction pharmacophore analysis was then performed for the compounds exhibiting good binding scores to evaluate their protein–ligand interactions. The selected protein–ligand complexes were subjected to molecular dynamics simulation for 50 ns. Results of binding free energy analysis revealed that two compounds—β-amyrin and stigmasta-5,22-dien-3-ol—exhibited the best binding interactions and stability. Finally, absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies were performed to understand the pharmacokinetic properties and safety profile of the compounds. The overall results indicate that the phytochemicals from Cyperus rotundus Linn, namely β-amyrin and stigmasta-5,22-dien-3-ol, can be screened as potential inhibitors of SARS-CoV-2 Mpro. [Display omitted] •Phytoconstituents from Cyperus rotundus Linn were retrieved to study as SARS-CoV-2 Mpro inhibitors.•Compounds were investigated for binding affinity and stability by docking and molecular dynamics approach.•Results identified β-amyrin and stigmasta-5,22-dien-3-ol as hit molecules.•Identified hit molecules were predicted for ADMET and drug likeness properties.