Identification of a New Potential SARS-COV-2 RNA-Dependent RNA Polymerase Inhibitor via Combining Fragment-Based Drug Design, Docking, Molecular Dynamics, and MM-PBSA Calculations

Frontiers in Chemistry
Mahmoud A El HassabWagdy M Eldehna

Abstract

The world has recently been struck by the SARS-Cov-2 pandemic, a situation that people have never before experienced. Infections are increasing without reaching a peak. The WHO has reported more than 25 million infections and nearly 857,766 confirmed deaths. Safety measures are insufficient and there are still no approved drugs for the COVID-19 disease. Thus, it is an urgent necessity to develop a specific inhibitor for COVID-19. One of the most attractive targets in the virus life cycle is the polymerase enzyme responsible for the replication of the virus genome. Here, we describe our Structure-Based Drug Design (SBDD) protocol for designing of a new potential inhibitor for SARS-COV-2 RNA-dependent RNA Polymerase. Firstly, the crystal structure of the enzyme was retrieved from the protein data bank PDB ID (7bv2). Then, Fragment-Based Drug Design (FBDD) strategy was implemented using Discovery Studio 2016. The five best generated fragments were linked together using suitable carbon linkers to yield compound MAW-22. Thereafter, the strength of the binds between compound MAW-22 and the SARS-COV-2 RNA-dependent RNA Polymerase was predicted by docking strategy using docking software. MAW-22 achieved a high docking score, even more ...Continue Reading

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Citations

Mar 23, 2021·International Journal of Peptide Research and Therapeutics·M A SiddiqaM V R Rao
Jun 2, 2021·International Journal of Biological Macromolecules·Galal MagdyAhmed M Abdel-Megied
Aug 31, 2021·Frontiers in Molecular Biosciences·Edward KingRay Luo

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Software Mentioned

gmx genion
discovery Studio
Discovery
MmPbSaStat
GROningen MAchine for Chemical Simulations ( GROMACS
MCSS ( Multiple Copy Simultaneous Search )
Preadmet
mmpbsa
PBSA
Discovery studio visualizer

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