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A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike | |
2019-04 | |
发表期刊 | SCIENCE ADVANCES |
ISSN | 2375-2548 |
卷号 | 5期号:4 |
发表状态 | 已发表 |
DOI | 10.1126/sciadv.aav4580 |
摘要 | Continuously emerging highly pathogenic human coronaviruses (HCoVs) remain a major threat to human health, as illustrated in past SARS-CoV and MERS-CoV outbreaks. The development of a drug with broad-spectrum HCoV inhibitory activity would address this urgent unmet medical need. Although previous studies have suggested that the HR1 of HCoV spike (S) protein is an important target site for inhibition against specific HCoVs, whether this conserved region could serve as a target for the development of broad-spectrum pan-CoV inhibitor remains controversial. Here, we found that peptide OC43-HR2P, derived from the HR2 domain of HCoV-OC43, exhibited broad fusion inhibitory activity against multiple HCoVs.EK1, the optimized form of OC43-HR2P, showed substantially improved pan-CoV fusion inhibitory activity and pharmaceutical properties. Crystal structures indicated that EK1 can form a stable six-helix bundle structure with both short alpha-HCoV and long beta-HCoV HR1s, further supporting the role of HR1 region as a viable pan-CoV target site. |
收录类别 | SCI ; SCIE ; EI |
资助项目 | Shanghai Rising-Star Program[16QA1400300] |
WOS研究方向 | Science & Technology - Other Topics |
WOS类目 | Multidisciplinary Sciences |
WOS记录号 | WOS:000466398400058 |
出版者 | AMER ASSOC ADVANCEMENT SCIENCE |
EI入藏号 | 20191806847509 |
EI主题词 | Crystal structure |
EI分类号 | Health Care:461.7 ; Crystal Lattice:933.1.1 |
WOS关键词 | RESPIRATORY SYNDROME CORONAVIRUS ; HIV-1 VIRION FUSION ; BAT CORONAVIRUSES ; NL63 INFECTION ; COILED-COIL ; SARS-COV ; PROTEIN ; PEPTIDES ; ENTRY ; CORE |
原始文献类型 | Article |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/45558 |
专题 | 生命科学与技术学院_博士生 免疫化学研究所_特聘教授组_抗体结构学实验室 免疫化学研究所_PI研究组_杨贝组 |
共同第一作者 | Yan, Lei; Xu, Wei |
通讯作者 | Wilson, Ian A.; Jiang, Shibo; Yang, Bei; Lu, Lu |
作者单位 | 1.Fudan Univ, Shanghai Publ Hlth Clin Ctr, Shanghai 200032, Peoples R China 2.Fudan Univ, Sch Basic Med Sci, Shanghai 200032, Peoples R China 3.Fudan Univ, Key Lab Med Mol Virol MOE MOH, Shanghai 200032, Peoples R China 4.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China 5.Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA 6.Jazan Univ, Dept Med Labs Technol, Coll Appl Med Sci, Jazan, Saudi Arabia 7.New York Blood Ctr, Lindsley F Kimball Res Inst, New York, NY 10065 USA 8.Chinese Ctr Dis Control & Prevent, MOH Key Lab Med Virol, Natl Inst Viral Dis Control & Prevent, Beijing, Peoples R China 9.Scripps Res Inst, Dept Integrat Struct & Computat Biol, 10550 North Torrey Pines Rd,BCC206, La Jolla, CA 92037 USA 10.Scripps Res Inst, Skaggs Inst Chem Biol, 10550 North Torrey Pines Rd,BCC206, La Jolla, CA 92037 USA |
通讯作者单位 | 免疫化学研究所 |
推荐引用方式 GB/T 7714 | Xia, Shuai,Yan, Lei,Xu, Wei,et al. A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike[J]. SCIENCE ADVANCES,2019,5(4). |
APA | Xia, Shuai.,Yan, Lei.,Xu, Wei.,Agrawal, Anurodh Shankar.,Algaissi, Abdullah.,...&Lu, Lu.(2019).A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike.SCIENCE ADVANCES,5(4). |
MLA | Xia, Shuai,et al."A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike".SCIENCE ADVANCES 5.4(2019). |
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