Evaluation of acridinedione analogs as potential SARS-CoV-2 main protease inhibitors and their comparison with repurposed anti-viral drugs

Computers in Biology and Medicine
Vijay Kumar BhardwajRituraj Purohit

Abstract

The main protease (Mpro) of SARS-CoV-2 is involved in the processing of vital polypeptides required for viral genome replication and transcription and is one of the best-characterized targets to inhibit the progression of SARS-CoV-2 in infected individuals. We screened a set of novel classes of acridinediones molecules to efficiently bind and inhibit the activity of the SARS-CoV-2 by targeting the Mpro. The repurposed FDA-approved antivirals were taken as standard molecules for this study. Long term (1.1 μs) MD simulations were performed to analyze the conformational space of the binding pocket of Mpro bound to the selected molecules. The molecules DSPD-2 and DSPD-6 showed more favorable MM-PBSA interaction energies and were seated more deeply inside the binding pocket of Mpro than the topmost antiviral drug (Saquinavir). Moreover, DSPD-5 also exhibited comparable binding energy to Saquinavir. The analysis of per residue contribution energy and SASA studies indicated that the molecules showed efficient binding by targeting the S1 subsite of the Mpro binding pocket. The DSPD-2, DSPD-6, and DSPD-5 could be developed as potential inhibitors of SARS-CoV-2. Moreover, we suggest that targeting molecules to bind effectively to the S1 ...Continue Reading

Citations

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Methods Mentioned

BETA
in-silico methods

Software Mentioned

PBSA
ADMET
CDOCKER
Komputer Assisted Technology ( TOPKAT )
SASA
Discovery
MM
ADMET Prediction by
GlycoBioChem PRODRG2
Discovery Studio

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