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 (M
pro
) 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 M
pro
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 M
pro
.
The viral disease dengue is transmitted by the Aedes mosquito and is commonly seen to occur in the tropical and subtropical regions of the world. It is a growing public health concern. To date, other than supportive treatments, there are no specific antiviral treatments to combat the infection. Therefore, finding potential compounds that have antiviral activity against the dengue virus is essential. The NS2B-NS3 dengue protease plays a vital role in the replication and viral assembly. If the functioning of this protease were to be obstructed then viral replication would be halted. As a result, this NS2B-NS3 proves to be a promising target in the process of anti-viral drug design. Through this study, we aim to provide suggestions for compounds that may serve as potent inhibitors of the dengue NS2B-NS3 protein. Here, a ligand-based pharmacophore model was generated and the ZINC database was screened through ZINCPharmer to identify molecules with similar features. 2D QSAR model was developed and validated using reported 4-Benzyloxy Phenyl Glycine derivatives and was utilized to predict the IC50 values of unknown compounds. Further, the study is extended to molecular docking to investigate interactions at the active pocket of the target protein. ZINC36596404 and ZINC22973642 showed a predicted pIC50 of 6.477 and 7.872, respectively. They also showed excellent binding with NS3 protease as is evident from their binding energy of −8.3and −8.1 kcal/mol, respectively. ADMET predictionsofcompounds have shown high drug-likeness. Finally, the molecular dynamic simulations integrated with MM-PBSA binding energy calculations confirmedboth identified ZINC compounds as potential hit moleculeswith good stability.
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