No commercially available drug candidate has yet been devised which is unique to and not repurposed against SARS-CoV-2 and has high efficacy or safe toxicity profile or both. Taking curcumin as a reference compound, we identified a new commercially available cyclohexanone compound, ZINC07333416 with binding energy (−8.72 kcal/mol) better than that of popularly devised anti-Covid-19 drugs like viral protease inhibitor Lopinavir, nucleoside analogue Remdesivir and the repurposed drug hydroxychloroquine when targeted to the active-site of SARS-CoV-2 Main protease (Mpro) through docking studies. The ligand ZINC07333416 exhibits crucial interactions with major active site residues of SARS-CoV-2 Mpro viz. Cys145 and His41 involving in the protease activity; as well as GLU-166 and ASN-142 which plays the pivotal role in the protein-dimerization. The protein-ligand stable interaction was further confirmed with molecular dynamics simulation (MDS) studies. Based on virtual assessment, ZINC07333416 also have significant values in terms of medicinal chemistry, pharmacokinetics, synthetic accessibility and anti-viral activity that encourage its experimental applications against COVID-19.

目前还没有设计出针对 SARS-CoV-2 的独特且未改用并具有高效或安全毒性特征或两者兼而有之的商用候选药物。以姜黄素作为参考化合物，我们确定了一种新的市售环己酮化合物 ZINC07333416，其结合能 (-8.72 kcal/mol) 优于普遍设计的抗-通过对接研究靶向 SARS-CoV-2 主蛋白酶 (Mpro) 的活性位点时，Covid-19 药物，如病毒蛋白酶抑制剂 Lopinavir、核苷类似物 Remdesivir 和改用药物羟氯喹。配体 ZINC07333416 与 SARS-CoV-2 Mpro 的主要活性位点残基表现出至关重要的相互作用。Cys145和His41参与蛋白酶活性；以及在蛋白质二聚化中起关键作用的 GLU-166 和 ASN-142。分子动力学模拟 (MDS) 研究进一步证实了蛋白质-配体稳定的相互作用。基于虚拟评估，ZINC07333416 在药物化学、药代动力学、合成可及性和抗病毒活性方面也具有重要价值，鼓励其针对 COVID-19 的实验应用。