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Antiviral Res . A bivalent form of a RBD-specific synthetic antibody effectively neutralizes SARS-CoV-2 variants

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  • Antiviral Res . A bivalent form of a RBD-specific synthetic antibody effectively neutralizes SARS-CoV-2 variants

    Antiviral Res


    . 2023 Nov 7:105738.
    doi: 10.1016/j.antiviral.2023.105738. Online ahead of print. A bivalent form of a RBD-specific synthetic antibody effectively neutralizes SARS-CoV-2 variants

    Dong-Gun Kim 1 , Uijin Kim 2 , In Ho Park 3 , Bumhan Ryu 4 , Youngki Yoo 2 , Jeong Seok Cha 2 , Ga-Yeon Yoon 2 , Sung-Hee Kim 5 , Heeju Oh 5 , Jun-Young Seo 5 , Ki Taek Nam 5 , Je Kyung Seong 6 , Jeon-Soo Shin 7 , Hyun-Soo Cho 8 , Hak-Sung Kim 9



    AffiliationsAbstract

    Coronavirus Disease 2019 (COVID-19) pandemic is severely impacting the world, and tremendous efforts have been made to deal with it. Despite many advances in vaccines and therapeutics, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants remains an intractable challenge. We present a bivalent Receptor Binding Domain (RBD)-specific synthetic antibody, specific for the RBD of wild-type (lineage A), developed from a non-antibody protein scaffold composed of LRR (Leucine-rich repeat) modules through phage display. We further reinforced the unique feature of the synthetic antibody by constructing a tandem dimeric form. The resulting bivalent form showed a broader neutralizing activity against the variants. The in vivo neutralizing efficacy of the bivalent synthetic antibody was confirmed using a human ACE2-expressing mouse model that significantly alleviated viral titer and lung infection. The present approach can be used to develop a synthetic antibody showing a broader neutralizing activity against a multitude of SARS-CoV-2 variants.

    Keywords: Cryo-EM; Receptor binding domain (RBD) variant; Repebody; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); Synthetic antibody.

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