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Antibody engineering improves neutralization activity against K417 spike mutant SARS-CoV-2 variants.
Li, Lili; Gao, Meiling; Jiao, Peng; Zu, Shulong; Deng, Yong-Qiang; Wan, Dingyi; Cao, Yang; Duan, Jing; Aliyari, Saba R; Li, Jie; Shi, Yueyue; Rao, Zihe; Qin, Cheng-Feng; Guo, Yu; Cheng, Genhong; Yang, Heng.
  • Li L; Institute of Systems Medicine, Chinese Academy of Medical Science & Peking Union College, Beijing, 100005, China.
  • Gao M; Suzhou Institute of Systems Medicine, Suzhou, 215123, China.
  • Jiao P; Institute of Systems Medicine, Chinese Academy of Medical Science & Peking Union College, Beijing, 100005, China.
  • Zu S; Suzhou Institute of Systems Medicine, Suzhou, 215123, China.
  • Deng YQ; State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin, 300071, China.
  • Wan D; Institute of Systems Medicine, Chinese Academy of Medical Science & Peking Union College, Beijing, 100005, China.
  • Cao Y; Suzhou Institute of Systems Medicine, Suzhou, 215123, China.
  • Duan J; Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing, 100071, China.
  • Aliyari SR; AtaGenix Laboratories (Wuhan) Co., Ltd, Wuhan, 430075, China.
  • Li J; Center of Growth, Metabolism and Aging, Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610065, China.
  • Shi Y; AtaGenix Laboratories (Wuhan) Co., Ltd, Wuhan, 430075, China.
  • Rao Z; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA, 90095, USA.
  • Qin CF; Department of Laboratory Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, China.
  • Guo Y; Institute of Systems Medicine, Chinese Academy of Medical Science & Peking Union College, Beijing, 100005, China.
  • Cheng G; Suzhou Institute of Systems Medicine, Suzhou, 215123, China.
  • Yang H; State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin, 300071, China.
Cell Biosci ; 12(1): 63, 2022 May 17.
Article in English | MEDLINE | ID: covidwho-1846866
ABSTRACT

BACKGROUND:

Neutralizing antibodies are approved drugs to treat coronavirus disease-2019 (COVID-19) patients, yet mutations in severe acute respiratory syndrome coronavirus (SARS-CoV-2) variants may reduce the antibody neutralizing activity. New monoclonal antibodies (mAbs) and antibody remolding strategies are recalled in the battle with COVID-19 epidemic.

RESULTS:

We identified multiple mAbs from antibody phage display library made from COVID-19 patients and further characterized the R3P1-E4 clone, which effectively suppressed SARS-CoV-2 infection and rescued the lethal phenotype in mice infected with SARS-CoV-2. Crystal structural analysis not only explained why R3P1-E4 had selectively reduced binding and neutralizing activity to SARS-CoV-2 variants carrying K417 mutations, but also allowed us to engineer mutant antibodies with improved neutralizing activity against these variants. Thus, we screened out R3P1-E4 mAb which inhibits SARS-CoV-2 and related mutations in vitro and in vivo. Antibody engineering improved neutralizing activity of R3P1-E4 against K417 mutations.

CONCLUSION:

Our studies have outlined a strategy to identify and engineer neutralizing antibodies against SARS-CoV-2 variants.
Keywords

Full text: Available Collection: International databases Database: MEDLINE Topics: Variants Language: English Journal: Cell Biosci Year: 2022 Document Type: Article Affiliation country: S13578-022-00794-7

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Full text: Available Collection: International databases Database: MEDLINE Topics: Variants Language: English Journal: Cell Biosci Year: 2022 Document Type: Article Affiliation country: S13578-022-00794-7