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A potent bispecific nanobody protects hACE2 mice against SARS-CoV-2 infection via intranasal administration.
Wu, Xilin; Cheng, Lin; Fu, Ming; Huang, Bilian; Zhu, Linjing; Xu, Shijie; Shi, Haixia; Zhang, Doudou; Yuan, Huanyun; Nawaz, Waqas; Yang, Ping; Hu, Qinxue; Liu, Yalan; Wu, Zhiwei.
  • Wu X; Center for Public Health Research, Medical School, Nanjing University, Nanjing, People's Republic of China; Department of Antibody, Abrev Biotechnology Co., Ltd., Nanjing, People's Republic of China.
  • Cheng L; Institute for Hepatology, National Clinical Research Center for Infectious, Disease, Shenzhen Third People's Hospital, Shenzhen, People's Republic of China.
  • Fu M; State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, People's Republic of China; Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou 510623, China.
  • Huang B; Center for Public Health Research, Medical School, Nanjing University, Nanjing, People's Republic of China.
  • Zhu L; Department of Antibody, Abrev Biotechnology Co., Ltd., Nanjing, People's Republic of China.
  • Xu S; Center for Public Health Research, Medical School, Nanjing University, Nanjing, People's Republic of China; Department of Antibody, Abrev Biotechnology Co., Ltd., Nanjing, People's Republic of China.
  • Shi H; Department of Antibody, Y-clone Medical Science Co. Ltd., Suzhou, People's Republic of China.
  • Zhang D; Department of Antibody, Abrev Biotechnology Co., Ltd., Nanjing, People's Republic of China.
  • Yuan H; Department of Antibody, Abrev Biotechnology Co., Ltd., Nanjing, People's Republic of China.
  • Nawaz W; Center for Public Health Research, Medical School, Nanjing University, Nanjing, People's Republic of China.
  • Yang P; State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, People's Republic of China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing, People's Republic of China.
  • Hu Q; State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, People's Republic of China; Institute for Infection and Immunity, St George's University of London, London SW17 0RE, UK.
  • Liu Y; State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, People's Republic of China. Electronic address: liuyl@wh.iov.cn.
  • Wu Z; School of Life Sciences, Ningxia University, Yinchuan, People's Republic of China; Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, People's Republic of China; State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, People
Cell Rep ; 37(3): 109869, 2021 10 19.
Article in English | MEDLINE | ID: covidwho-1517084
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ABSTRACT
The dramatically expanding coronavirus disease 2019 (COVID-19) needs multiple effective countermeasures. Neutralizing nanobodies (Nbs) are a potential therapeutic strategy for treating COVID-19. Here, we characterize several receptor binding domain (RBD)-specific Nbs isolated from an Nb library derived from an alpaca immunized with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (S); among them, three Nbs exhibit picomolar potency against SARS-CoV-2 live virus, pseudotyped viruses, and circulating SARS-CoV-2 variants. To improve their efficacy, various configurations of Nbs are engineered. Nb15-NbH-Nb15, a trimer constituted of three Nbs, is constructed to be bispecific for human serum albumin (HSA) and RBD of SARS-CoV-2. Nb15-NbH-Nb15 exhibits single-digit ng/ml neutralization potency against the wild-type and Delta variants of SARS-CoV-2 with a long half-life in vivo. In addition, we show that intranasal administration of Nb15-NbH-Nb15 provides effective protection for both prophylactic and therapeutic purposes against SARS-CoV-2 infection in transgenic hACE2 mice. Nb15-NbH-Nb15 is a potential candidate for both the prevention and treatment of SARS-CoV-2 through respiratory administration.
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Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Main subject: Administration, Intranasal / Antibodies, Bispecific / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / COVID-19 Subject: Administration, Intranasal / Antibodies, Bispecific / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / COVID-19 Language: English Journal: Cell Rep Year: 2021

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Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Main subject: Administration, Intranasal / Antibodies, Bispecific / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / COVID-19 Subject: Administration, Intranasal / Antibodies, Bispecific / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / COVID-19 Language: English Journal: Cell Rep Year: 2021
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