以SARS-CoV-2膜融合过程6-HB核心为靶标的多肽类融合抑制剂的研究进展

RESEARCH PROGRESS ON PEPTIDE-BASED FUSION INHIBITORS TARGETING THE 6-HB CORE OF SARS-CoV-2 MEMBRANE FUSION PROCESS

由新型冠状病毒(SARS-CoV-2)引起的新型冠状病毒肺炎对人类健康产生了深远的影响,不断出现的SARS-CoV-2变异株持续威胁全球公共卫生安全。因此,抗SARS-CoV-2药物的研发需求十分迫切。SARSCoV-2包膜在与宿主细胞膜融合过程中会形成六股螺旋束(6-HB),以6-HB或组成6-HB的HR1/HR2区域为靶标能够成功设计一系列多肽类融合抑制剂。本文综述了SARS-CoV-2的6-HB构效关系及多肽类融合抑制剂的设计思路和改造方法,以期为开发抗SARS-CoV-2药物提供新的研究思路。

Corona virus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2)has profoundly affected human health.Meanwhile,the continuously arising of SARS-CoV-2 has been posting a continuing threat to public health safety globally.Therefore,it is urgent to develop anti-SARS-CoV-2 agents.SARS-CoV-2 envelope forms a six-helix bundle(6-HB)structure during the membrane fusion process with the host cell.A series of peptidebased fusion inhibitors have been successfully obtained by targeting the 6-HB or the HR1/HR2 regions composing 6-HB.This paper reviewed the structure-activity relationship of the SARS-CoV-26-HB and the design ideas and retrofitting methods of peptide-based fusion inhibitors.We hope that this review will provide new research insights for the development of anti-SARS-CoV-2 agents.