Identification of potential agonist-like molecules for α2-adrenergic receptor by multi-layer virtual screening to combat sinusitis.

Sinusitis is one of the most common respiratory inflammatory conditions and a significant health issue that affects millions of people worldwide with a global prevalence of 10-15%. The side effects of available drug regimens of sinus infection demand the urgent development of new drug candidates to combat sinusitis. With the aim of identifying new drug-like candidates to control sinus, we have conducted multifold comprehensive screening of drug-like molecules targeting α2-adrenergic receptor (α2-AR), which serve as the primary drug target in sinusitis. By structure-based virtual screening of in-house compound's database, ten molecules (CP1-CP10) with agonistic effects for α2-AR were selected, and their binding mechanism with critical residues of α2-AR and their physicochemical properties were studied. Moreover, the process of receptor activation by these compounds and the conformational changes in α2-AR caused by these molecules, were further explored by molecular dynamic simulation. The MM-PBSA estimated free energies of compounds are higher than that of reference agonist (ΔG

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Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.