Computational Repurposing of Potential Dimerization Inhibitors against SARS-CoV-2 Main Protease

Subhomoi      Borkotoky; Archisha      Prakash; Gyan   Prakash   Modi; Vikash   Kumar   Dubey
doi:10.2174/1570180820666230111141203
Abstract

Background: The screening, design, and synthesis of various dimerization inhibitors have been an active area of interest for structure-based drug design efforts. Functionally important dimers, such as human immunodeficiency virus (HIV) protease and surviving, are being targeted for such studies over time. Computational repurposing of potential drug candidates provides a cost and time-efficient way in the drug discovery life cycle.
Objective: Concerning the current coronavirus disease (COVID-19) scenario, the functionally active dimer of SARS-CoV-2 (severe acute respiratory syndrome) main protease (Mpro) is used as a target to screen possible dimerization inhibitors.
Methods: A database of small molecule protein-protein interaction inhibitors was screened for the study. This study used molecular docking, followed by molecular dynamics (MD) simulation and postsimulation binding energy predictions.
Results: From the selected 183 compounds, a diazene-based compound and a salicylic-type compound were identified as possible dimerization inhibitors in this study. These two compounds formed stable complexes with the Mpro during the MD simulations. The complexes formed by these two compounds were also unable to form important salt bridge interactions required for the dimerization of the protomers.
Conclusion: Experimental studies on both compounds were previously conducted as dimerization inhibitors in HIV. The data led to the possibility of exploring the identified compounds as dimerization inhibitors, which could be important for SARS-CoV-2 therapeutics.
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DOI https://dx.doi.org/10.2174/1570180820666230111141203	Print ISSN 1570-1808
Publisher Name Bentham Science Publisher	Online ISSN 1875-628X
Letters in Drug Design & Discovery

Computational Repurposing of Potential Dimerization Inhibitors against SARS-CoV-2 Main Protease

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