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A panel of multivalent nanobodies broadly neutralizing Omicron subvariants and recombinant

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机构: [1]Department of Critical Medicine, School of Medicine, Shenzhen People's Hospital, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong, China. [2]NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China. [3]College of Integrative Medicine, Laboratory of Pathophysiology, Key Laboratory of Integrative Medicine on Chronic Diseases, Fujian University of Traditional Chinese Medicine, Fuzhou, China. [4]State Key Laboratory for Quality Assurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China. [5]School of Medicine, Zhongda Hospital, Southeast University, Nanjing, China. [6]Central Laboratory, Shanxi Province Hospital of Traditional Chinese Medicine, Taiyuan, China. [7]Department of Oncology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China. [8]State Key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng, Henan, China.
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关键词: multivalent neutralizing Nbs Omicron receptor‐binding domain SARS‐CoV‐2

摘要:
The emerging Omicron subvariants have a remarkable ability to spread and escape nearly all current monoclonal antibody (mAb) treatments. Although the virulence of SARS-CoV-2 has now diminished, it remains a significant threat to public health due to its high transmissibility and susceptibility to mutation. Therefore, it is urgent to develop broad-acting and potent therapeutics targeting current and emerging Omicron variants. Here, we identified a panel of Omicron BA.1 spike receptor-binding domain (RBD)-targeted nanobodies (Nbs) from a naive alpaca VHH library. This panel of Nbs exhibited high binding affinity to the spike RBD of wild-type, Alpha B.1.1.7, Beta B.1.351, Delta plus, Omicron BA.1, and BA.2. Through multivalent Nb construction, we obtained a subpanel of ultrapotent neutralizing Nbs against Omicron BA.1, BA.2, BF.7 and even emerging XBB.1.5, and XBB.1.16 pseudoviruses. Protein structure prediction and docking analysis showed that Nb trimer 2F2E5 targets two independent RBD epitopes, thus minimizing viral escape. Taken together, we obtained a panel of broad and ultrapotent neutralizing Nbs against Omicron BA.1, Omicron BA.2, BF.7, XBB.1.5, and XBB.1.16. These multivalent Nbs hold great promise for the treatment against SARS-CoV-2 infection and could possess a superwide neutralizing breadth against novel omicron mutants or recombinants.© 2024 Wiley Periodicals LLC.

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出版当年[2023]版:
大类 | 3 区 医学
小类 | 3 区 病毒学
最新[2025]版:
大类 | 3 区 医学
小类 | 3 区 病毒学
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第一作者机构: [1]Department of Critical Medicine, School of Medicine, Shenzhen People's Hospital, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong, China. [2]NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
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通讯机构: [1]Department of Critical Medicine, School of Medicine, Shenzhen People's Hospital, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong, China. [2]NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China. [4]State Key Laboratory for Quality Assurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China. [6]Central Laboratory, Shanxi Province Hospital of Traditional Chinese Medicine, Taiyuan, China. [7]Department of Oncology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China. [8]State Key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng, Henan, China. [*1]Central Laboratory, Shanxi Province Hospital of Traditional Chinese Medicine, Taiyuan 030012, China. [*2]Department of Critical Medicine, School of Medicine, Shenzhen People's Hospital, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong 518020, China [*3]NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
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