Comparative molecular investigation of the potential inhibitors against SARS-CoV-2 main protease: a molecular docking study

Abstract

Recent outbreak of novel coronavirus and its rapid pandemic escalation in all over the world has drawn the attention to urgent need for effective drug development. However, due to prolonged vaccine and drug development procedure against a newly emerged devastating SARS-CoV-2 virus pathogen, repurposing of existing potential pertinent drug molecules would be preferable strategy to reduce mortality immediately and further development of new drugs to combat overall global Covid-19 crisis in all over the world. Herein, we have filtered 23 prospective drug candidates through literature review. Assessing evidences from molecular docking studies, it was clearly seen that, Epirubicin, Vapreotida, and Saquinavir exhibited better binding affinity against SARS-CoV-2 Main Protease than other drug molecules among the 23 potential inhibitors. However, 50 ns molecular dynamics simulation indicated the less mobile nature of the docked complex maintaining structural integrity. Our overall prediction findings indicate that Epirubicin, Vapreotida, and Saquinavir may inhibit COVID-19 by synergistic interactions in the active cavity and those results can pave the way in drug discovery although it has to be further validated by in-vitro and in-vivo investigations.

Virtual screening and molecular dynamics simulation study of plant-derived compounds to identify potential inhibitors of main protease from SARS-CoV-2

“…Although several clinical trials have been undergoing, the drug development methods are time-consuming and costly, there is a need for fast and effective development of active antiviral agents. Conversely, computer-aided drug design may assist the researcher to find the new therapeutic agent against SARS-CoV-2 due to its rapid and accurate screening capability from a vast small molecule library [ 50–52 ]. Due to having a large impact on the function of SARS-CoV-2, the M pro has become the best target for different therapeutic tactics.…”

A molecular modelling approach for identifying antiviral selenium-containing heterocyclic compounds that inhibit the main protease of SARS-CoV-2: an in silico investigation

“…Finally, the simulation was performed for 100 ns, and after every 100 ps, the simulation trajectories were saved. The simulation trajectories were analysed to calculate root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA) and hydrogen bonds ( 58–60 ).…”

Efficacy of Phytochemicals Derived from Avicennia officinalis for the Management of COVID-19: A Combined In Silico and Biochemical Study

“…The crystal structure of the SARS-CoV-2 main protease (M pro ) was recently submitted to the Protein Data Bank (PDB) [ 7 ], revealing 11 putative sites of injection, consisting of type-I (Chymotrypsin), type-II (Picornavirus), and type-III domains. The type-I and type-II domains consist of six-stranded antiparallel β-barrels containing H-41 and C-145 active sites [ 10 ], whereas the type-III domain contains α-helices [ 11 ]. The SARS-CoV-2 life cycle depends on M pro activity, and the absence of the M pro protein in humans makes this protein a promising target for vaccine development [ 12 , 13 , 14 ].…”