Discovery, synthesis and in silico approach of pyrrolo [3,4- c ]pyrroles as SARS-CoV-2 m ^pro inhibitors

Abstract

A new series of pyrrolo [3,2-c] pyrroles were synthesized and characterized using various analytical techniques including FT-IR, UV-Vis and NMR spectroscopic studies. The biological descriptors of the synthesized compounds were investigated using DFT calculation. The mode of binding and reactivity of the target compounds with SARS-CoV-2 main protease (M pro ) were studied using molecular docking and molecular dynamics (MD) simulation. Molecular docking of the compounds (4a and 5a) showed a promising binding a nity towards M pro protein with the binding energy of -8.3 kcal/mol and − 8.0 kcal/mol, respectively. The results of MD simulation and prime MM-GBSA calculation were consistent with molecular docking. The absorption, distribution, metabolism, excretion (ADME) properties of the compounds are in the acceptable range, as they are orally active and obey Lipinski's rule of ve without violation. In addition, in silico toxicity prediction using the Pro-Tox II revealed the non-toxic nature of the compounds. Hence the obtained results suggest that these compounds could be a possible anti-viral candidate and highlight this series of compounds for further drug design and development against SARS-CoV-2.

Assessing the Potential Contribution of In Silico Studies in Discovering Drug Candidates That Interact with Various SARS-CoV-2 Receptors

“…Their biological properties were assessed using DFT calculations and their binding and reactivity with the SARS-CoV-2 main protease (Mpro) was investigated through molecular docking and MD simulations. These findings indicate the potential of these compounds as anti-viral candidates, underscoring their significance for future drug design and development against SARS-CoV-2 [63]. These methods have been applied to study drug-receptor interactions for SARS-CoV-2, with the goal of identifying potential drug candidates to treat COVID-19 [64].…”