Repurposing of anti-lung cancer drugs as multi-target inhibitors of SARS-CoV-2 proteins: An insight from molecular docking and MD-simulation study.

Herein we have selected seventeen anti-lung cancer drugs to screen against Mpro, PLpro and spike glycoproteins of SARS-CoV-2to ascertain the potential therapeutic agent against COVID-19. ADMET profiling were employed to evaluate their pharmacokinetic properties. Molecular docking studies revealed that Capmatinib (CAP) showed highest binding affinity against the selected proteins of SARS-CoV-2. Molecular Dynamics (MD) simulation and the analysis of RMSD, RMSF, and binding energy confirmed the abrupt conformational changes of the proteins due to the presence of this drug. These findings provide an opportunity for doing advanced experimental research to evaluate the potential drug to combat COVID-19.

Inhibitory effect of anti-HIV compounds extracted from Indian medicinal plants to retard the replication and transcription process of SARS-CoV-2: an insight from molecular docking and MD-simulation studies.

Outbreak of Coronavirus (SARS-CoV-2) has thrown a big challenge to the globe by snatching millions of human lives from the world. In this study, inhibitory efficiency of ten anti-HIV compounds from different Indian medicinal plant parts have been virtually screened against Mpro, PLpro and RdRp proteins of SARS-CoV-2. The molecular docking study reflected that among these compounds, Proptine (PTP) has the highest binding affinity for the three cases. Introduction of PTP molecules within the binding pocket of these proteins showed a large structural and conformational changes on the structure of proteins which is revealed from molecular dynamics (MD) simulation studies. RMSD, RMSF and analysis of thermodynamic parameters also revealed that PTP makes a huge impact on the structures of the respective proteins which will pave an opportunity for doing advanced experimental research to evaluate the potential drug to combat COVID-19. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13721-021-00309-3.

Inhibitory efficacy of RNA virus drugs against SARS-CoV-2 proteins: An extensive study.

Herein we have made a comprehensive analysis of inhibitory efficacy of 16 RNA virus drugs against RdRp, Mpro and PLpro proteins of SARS-CoV-2. Analysis of docked conformation revealed that Baloxavir marboxil (BMX) corresponds to the highest binding energy. Analysis of residue confirmed that BMX strongly interact with these three proteins involving H-bonding, ionic as well as hydrophobic interactions. Molecular dynamics simulation and analysis of parameters like RMSD, RMSF, binding energy confirmed noticeable conformational alternation with these proteins with makeable effect on RdRp. The potentially inhibitory action of BMX against these three proteins suggests the inhibition of overall transcription process of SARS-CoV-2. These observation along with the recently observed inhibitory action of BMX on influenza with clinically proven no side effects emphasizes to uncover the role of BMX by in-vitro and in-vivo analysis.

Inhibitory efficiency of potential drugs against SARS-CoV-2 by blocking human angiotensin converting enzyme-2: Virtual screening and molecular dynamics study.

Till date millions of people are infected by SARS-CoV-2 throughout the world, while no potential therapeutics or vaccines are available to combat this deadly virus. Blocking of human angiotensin-converting enzyme 2 (ACE-2) receptor, the binding site of SARS-CoV-2 spike protein, an effective strategy to discover a drug for COVID-19. Herein we have selected 24 anti-bacterial and anti-viral drugs and made a comprehensive analysis by screened them virtually against ACE-2 receptor to find the best blocker by molecular docking and molecular dynamics studies. Analysis of results revealed that, Cefpiramide (CPM) showed the highest binding affinity of -9.1 kcal/mol. Furthermore, MD study for 10 ns and evaluation of parameters like RMSD, RMSF, radius of gyration, solvent accessible surface area analysis confirmed that CPM effectively binds and blocks ACE-2 receptor efficiently.

Screening of potential drug from Azadirachta Indica (Neem) extracts for SARS-CoV-2: An insight from molecular docking and MD-simulation studies.

Azadirachta Indica (Neem) extracts have been known for their anti-bacterial and other effects since ancient times. The present work examines the inhibitory activity of Neem extracts on Papain like protease (PLpro) of the novel coronavirus SARS-CoV-2. The activity is analysed by molecular docking study along with molecular dynamics simulation. All the studied Neem compounds showed decent level of inhibitory activity against PLpro of SARS-CoV-2. Among them, desacetylgedunin (DCG) found in Neem seed showed the highest binding affinity towards PLpro. Furthermore, MD-simulation studies supported by standard analysis (e.g. root mean square deviation and fluctuation (RMSD, RMSF), radius of gyration, solvent accessible surface area (SASA)) showed large impact on the structure of PLpro by DCG. We believe that the significant effect of DCG on PLpro may help in therapeutic efforts against SARS-CoV-2.