基于分子对接技术筛选低聚壳聚糖作为抗COVID-19潜在性药物

Screening of chitosan oligosaccharides as potential anti-COVID-19 drugs based on molecular docking technology

目的以SARS-CoV-2的Spike蛋白(S蛋白),血管紧张素转化酶-2(ACE2)和SARS-CoV-2的3CLpro水解酶为靶标,以壳聚糖为小分子,利用分子对接筛选S蛋白、ACE2阻断剂和3CLpro抑制剂,且指导以低聚壳聚糖作为SARS-CoV-2潜在的阻断剂和抑制剂的药物的研发。方法软件预测S蛋白,ACE2和3CLpro晶体结构模型上的活性位点,利用Glide分子对接技术虚拟筛选不同聚合度的壳聚糖,通过结合打分值以及与靶蛋白受体的相互作用模式,获得具有抗SARS-CoV-2潜在活性的低聚壳聚糖。结果壳二糖,壳三糖,壳四糖和壳五糖的理论数据确定低聚壳聚糖(聚合度≤5)与S蛋白,ACE2及3CLpro结合效果都较好,可作为COVID-19潜在的阻断剂和抑制剂。其与S蛋白,ACE2和3CLpro主要氨基酸以氢键和盐桥作用结合,聚合度>5的壳聚糖与S蛋白,ACE2及3CLpro没有结合。结论聚合度在2-5的壳聚糖作为S蛋白与ACE2结合阻断剂和3CLpro抑制剂具有潜在的抗COVID-19作用,揭示了S蛋白,ACE2和3CLpro与不同低聚壳聚糖结合的结合位点和作用形式,为后续以不同低聚壳聚糖作为COVID-19潜在的阻断剂和抑制剂的研究奠定坚实的理论基础。

Objective To target Spike protein(S pro) of COVID-19,angiotensin-converting enzyme-2(ACE2) and 3 CLpro hydrolase of SARS-CoV-2 as targets, and use chitosan as a small molecule to screen S pro, ACE2 blockers and 3 CLpro inhibitors by molecular docking, and guide the development of drugs that use oligochitosan as a potential blocker and inhibitor of SARS-CoV-2.Methods The software predicts the active sites on the crystal structure models of S pro, ACE2 and 3 CLpro, and uses Glide molecular docking technology to virtually screen chitosan with different degrees of polymerization.By combining the score and the interaction mode with the target protein receptor, we obtain anti-SARS-CoV-2 potential active oligomeric chitosan.Results The theoretical data of chitosan, chitosan, chitotetraose and Chitinpentaose confirmed that the combination of oligomeric chitosan(degree of polymerization ≤5) with S pro, ACE2 and 3 CLpro is good, and can be used as potential blockers of SARS-CoV-2 and inhibitors.It is combined with the main amino acids of S pro, ACE2 and 3 CLpro through hydrogen bonding and salt bridge interaction, while chitosan with a degree of polymerization >5 is not bound to S pro, ACE2 and3 CLpro.Conclusion Chitosan with a degree of polymerization of 2-5 has potential anti-SARS-CoV-2 effect as an Spro-ACE2 binding blocker and 3 CLpro inhibitor, revealing the binding of S pro, ACE2 and 3 CLpro to different oligomeric chitosan, and laying a solid theoretical foundation for the subsequent research studies on different oligomeric chitosan as potential blockers and inhibitors of SARS-CoV-2.