# Chromene-Thiazole Derivatives as Potential SARS-CoV‑2 Mpro Inhibitors: Synthesis and Computational Studies

## TL;DR

This paper reports the synthesis and computational evaluation of three chromene-thiazole compounds as potential inhibitors of the SARS-CoV-2 Mpro enzyme.

## Contribution

The study introduces new chromene-thiazole derivatives with promising inhibitory potential against SARS-CoV-2 Mpro, supported by experimental and computational analyses.

## Key findings

- The chromene-thiazole derivatives showed docking affinities comparable to or better than ML188, a known inhibitor.
- Molecular dynamics simulations confirmed stable interactions between the compounds and the Mpro enzyme.
- Key amino acid residues involved in ligand binding were identified through QM/MM calculations.

## Abstract

Three chromene-thiazole derivatives bearing benzimidazole,
benzothiazole,
and phenyl-1,2,4-triazole moieties were synthesized and evaluated
for their potential as SARS-CoV-2 Mpro inhibitors. The
derivatives were characterized by various spectroscopic and spectrometric
methods: FT-IR, 1H NMR, 13C NMR, HRMS. Density
functional theory (DFT) at the B3LYP/6–311++G­(3df,3pd) level
was used to calculate the optimized structures of the derivatives
and determine their electronic properties. Molecular docking analyses
of the derivatives with SARS-CoV-2 Mpro (PDB ID: 6LU7) indicate significant
interactions, with docking affinity scores ranging from −7.5
kcal/mol for the benzothiazole derivative to −8.4 kcal/mol
for the phenyl-1,2,4-triazole derivative. These docking scores are
comparable to or better than those of ML188 (−7.5 kcal/mol),
a potent SARS-CoV-2 Mpro inhibitor, indicating the inhibitory
potential of these derivatives. Molecular dynamics simulations and
QM/MM calculations of the derivatives confirmed the stability of the
protein–ligand interactions, and highlighted the key amino
acid residues involved in stabilization.