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

tetano

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



Affiliations
Abstract

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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