Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion

Vista sencilla de ítem
dc.creatorXia, Shuai
dc.creatorLiu, Meiqin
dc.creatorWang, Chao
dc.creatorXu, Wei
dc.creatorLan, Qiaoshuai
dc.creatorFeng, Siliang
dc.creatorQi, Feifei
dc.creatorBao, Linlin
dc.creatorDu, Lanying
dc.creatorLiu, Shuwen
dc.creatorQin, Chuan
dc.creatorSun, Fei
dc.creatorShi, Zhengli
dc.creatorZhu, Yun
dc.creatorJiang, Shibo
dc.creatorLu Lu
dc.date.accessioned2020-08-24T18:07:44Z
dc.date.available2020-08-24T18:07:44Z
dc.date.created2020-03-30
dc.description.abstractenglishThe recent outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 infection in Wuhan, China has posed a serious threat to global public health. To develop specific anti-coronavirus therapeutics and prophylactics, the molecular mechanism that underlies viral infection must first be defined. Therefore, we herein established a SARS-CoV-2 spike (S) protein-mediated cell–cell fusion assay and found that SARS-CoV-2 showed a superior plasma membrane fusion capacity compared to that of SARS-CoV. We solved the X-ray crystal structure of six-helical bundle (6-HB) core of the HR1 and HR2 domains in the SARS-CoV-2 S protein S2 subunit, revealing that several mutated amino acid residues in the HR1 domain may be associated with enhanced interactions with the HR2 domain. We previously developed a pan-coronavirus fusion inhibitor, EK1, which targeted the HR1 domain and could inhibit infection by divergent human coronaviruses tested, including SARS-CoV and MERS-CoV. Here we generated a series of lipopeptides derived from EK1 and found that EK1C4 was the most potent fusion inhibitor against SARS-CoV-2 S protein-mediated membrane fusion and pseudovirus infection with IC50s of 1.3 and 15.8 nM, about 241- and 149-fold more potent than the original EK1 peptide, respectively. EK1C4 was also highly effective against membrane fusion and infection of other human coronavirus pseudoviruses tested, including SARS-CoV and MERS-CoV, as well as SARSr-CoVs, and potently inhibited the replication of 5 live human coronaviruses examined, including SARS-CoV-2. Intranasal application of EK1C4 before or after challenge with HCoV-OC43 protected mice from infection, suggesting that EK1C4 could be used for prevention and treatment of infection by the currently circulating SARS-CoV-2 and other emerging SARSr-CoVs.spa
dc.format.extent13 páginas.spa
dc.format.mimetypeapplication/pdfspa
dc.identifier.doihttps://doi.org/10.1038/s41422-020-0305-xspa
dc.identifier.otherhttps://www.nature.com/articles/s41422-020-0305-xspa
dc.identifier.urihttps://hdl.handle.net/20.500.12010/12157
dc.language.isoengspa
dc.publisherCell Researchspa
dc.rights.accessrightsinfo:eu-repo/semantics/restrictedAccessspa
dc.rights.localAcceso restringidospa
dc.sourcereponame:Expeditio Repositorio Institucional UJTLspa
dc.sourceinstname:Universidad de Bogotá Jorge Tadeo Lozanospa
dc.subjectInhibition of SARS-CoV-2 (previously 2019-nCoV) infectionspa
dc.subjectviral infectionspa
dc.subject.lembSíndrome respiratorio agudo gravespa
dc.subject.lembCOVID-19spa
dc.subject.lembSARS-CoV-2spa
dc.subject.lembCoronavirusspa
dc.titleInhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusionspa
dc.type.coarhttp://purl.org/coar/resource_type/c_6501spa
dc.type.hasversioninfo:eu-repo/semantics/acceptedVersionspa
dc.type.localArtículospa

Archivos

Bloque original

Mostrando 1 - 1 de 1
Miniatura
Nombre:
Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection.pdf
Tamaño:
5.38 MB
Formato:
Adobe Portable Document Format
Descripción:
Articulo de Revista
Descargar

Bloque de licencias

Mostrando 1 - 1 de 1
Miniatura
Nombre:
license.txt
Tamaño:
2.87 KB
Formato:
Item-specific license agreed upon to submission
Descripción:
Descargar

Colecciones

Documentos científicos relacionados a la COVID-19

Carrera 4 # 22-61 Teléfono: (+57) 601 242 7030 - 018000111022 Fax: (+57) 601 561 2107 Bogotá D.C., Colombia

Fundación Universitaria de Bogotá Jorge Tadeo Lozano | Vigilada Mineducación

Institución de educación superior privada, de utilidad común, sin ánimo de lucro y su carácter académico es el de Universidad

Reconocimiento personería jurídica: Resolución 2613 del 14 de agosto de 1959 Minjusticia.

Institución de Educación Superior sujeta a inspección y vigilancia por el Ministerio de Educación Nacional.

Software DSpace copyright © 2002-2026 LYRASIS