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SARS-CoV-2 Omicron XBB subvariants exhibit enhanced fusogenicity and substantial immune evasion in elderly population, but high sensitivity to pan-coronavirus fusion inhibitors.
Xia, Shuai; Jiao, Fanke; Wang, Lijue; Yu, Xueying; Lu, Tianyu; Fu, Yan; Huang, Ziqi; Li, Xicheng; Huang, Jinghe; Wang, Qian; Man, Qiuhong; Xiong, Lize; Jiang, Shibo; Lu, Lu.
Afiliación
  • Xia S; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Fudan University, Shanghai, China.
  • Jiao F; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Fudan University, Shanghai, China.
  • Wang L; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Fudan University, Shanghai, China.
  • Yu X; Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
  • Lu T; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Fudan University, Shanghai, China.
  • Fu Y; Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
  • Huang Z; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Fudan University, Shanghai, China.
  • Li X; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Fudan University, Shanghai, China.
  • Huang J; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Fudan University, Shanghai, China.
  • Wang Q; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Fudan University, Shanghai, China.
  • Man Q; Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
  • Xiong L; Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
  • Jiang S; Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
  • Lu L; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Fudan University, Shanghai, China.
J Med Virol ; 95(3): e28641, 2023 03.
Article en En | MEDLINE | ID: mdl-36890632
Numerous emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants have shown significant immune evasion capacity and caused a large number of infections, as well as vaccine-breakthrough infections, especially in elderly populations. Recently emerged Omicron XBB was derived from the BA.2 lineage, but bears a distinct mutant profile in its spike (S) protein. In this study, we found that Omicron XBB S protein drove more efficient membrane-fusion kinetics on human lung-derived cells (Calu-3). Considering the high susceptibility of the elderly to the current Omicron pandemic, we performed a comprehensive neutralization assessment of elderly convalescent or vaccine sera against XBB infection. We found that the sera from elderly convalescent patients who experienced with BA.2 infection or breakthrough infection potently inhibited BA.2 infection, but showed significantly reduced efficacy against XBB. Moreover, recently emerged XBB.1.5 subvariant also showed more significant resistance to the convalescent sera of BA.2- or BA.5-infected elderly. On the other hand, we found that the pan-CoV fusion inhibitors EK1 and EK1C4 can potently block either XBB-S- or XBB.1.5-S-mediated fusion process and viral entry. Moreover, EK1 fusion inhibitor showed potent synergism when combined with convalescent sera of BA.2- or BA.5-infected patients against XBB and XBB.1.5 infection, further indicating that EK1-based pan-CoV fusion inhibitors are promising candidates for development as clinical antiviral agents to combat the Omicron XBB subvariants.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: SARS-CoV-2 / COVID-19 Tipo de estudio: Diagnostic_studies Límite: Aged / Humans Idioma: En Revista: J Med Virol Año: 2023 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: SARS-CoV-2 / COVID-19 Tipo de estudio: Diagnostic_studies Límite: Aged / Humans Idioma: En Revista: J Med Virol Año: 2023 Tipo del documento: Article País de afiliación: China