抗新型冠状病毒靶点及药物研究进展

Research progress in targets and drugs for novel coronavirus

新型冠状病毒肺炎(COVID-19)是由严重急性呼吸综合征冠状病毒新型冠状病毒(SARS-CoV-2)引起的严重威胁人类健康的传染性疾病。SARS-CoV-2的病毒颗粒由外层的包膜和内层的核衣壳两部分构成,其基因组编码的非结构蛋白和结构蛋白在其吸附、穿入、脱壳、核酸和蛋白质合成、装配和释放整个生命周期中发挥重要作用,针对病毒自身或其感染依赖的宿主分子均可研发抗病毒药物。靶向SARS-CoV-2刺突糖蛋白的抗体药物和靶向SARS-CoV-2 RNA聚合酶的小分子药物等表现出一定的抗病毒作用,是潜力较大的候选药物,但其疗效仍有待进一步临床试验证明。综合考虑病毒自身和宿主靶点,进行多靶点多药物组合可能会取得更佳的防治效果。本综述对SARS-CoV-2的结构和生命周期、潜在的靶点和药物等研究进展进行综述,为研发抗SARS-CoV-2药物提供参考。

The outbreak of coronavirus disease-19(COVID-19)caused by novel coronavirus(severe acute respiratory syndrome coronavirus-2,SARS-CoV-2)has posed a serious threat to public health.Virus particles of SARS-CoV-2 are composed of outer envelopes and inner nucleocapsids.The nonstructural and structural proteins encoded by the genome play an important role in the whole life cycle of their adsorption,penetration,uncoating,synthesis of nucleic acids and proteins,assembly and liberation.Antiviral drugs can be developed to target the virus itself or key host molecules for virus infection.So far,antibody drugs targeting spike glycoprotein S and small molecule drugs targeting RNA polymerase have shown antiviral effects.They are currently more promising candidate drugs.However,their efficacy still needs to be proved by further clinical trials,and miracle antiviral drugs have not yet appeared.Considering the virus and host targets,the combination therapy of multi-targets and multidrugs,may achieve better therapeutic effect.In this paper,the structure and life cycle of SARS-CoV-2,the research progress in potential targets and drugs were reviewed to provide useful information for the development of anti-SARS-CoV-2 drugs.