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TitleA bivalent form of a RBD-specific synthetic antibody effectively neutralizes SARS-CoV-2 variants.
Journal, issue, pagesAntiviral Res, Vol. 220, Page 105738, Year 2023
Publish dateNov 8, 2023
AuthorsDong-Gun Kim / Uijin Kim / In Ho Park / Bumhan Ryu / Youngki Yoo / Jeong Seok Cha / Ga-Yeon Yoon / Sung-Hee Kim / Heeju Oh / Jun-Young Seo / Ki Taek Nam / Je Kyung Seong / Jeon-Soo Shin / Hyun-Soo Cho / Hak-Sung Kim /
PubMed AbstractCoronavirus 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 ...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.
External linksAntiviral Res / PubMed:37944822
MethodsEM (single particle) / X-ray diffraction
Resolution1.96 - 3.3 Å
Structure data

EMDB-34501, PDB-8h6f:
Cryo-EM structure of SARS-CoV-2 Spike protein in complex with A6 repebody
Method: EM (single particle) / Resolution: 3.3 Å

PDB-7yco:
Crystal structure of SARS-CoV-2 Receptor Binding Domain bound to A6 repebody
Method: X-RAY DIFFRACTION / Resolution: 1.96 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-HOH:
WATER

Source
  • severe acute respiratory syndrome coronavirus 2
  • cyclostomatida (invertebrata)
KeywordsPROTEIN BINDING / Severe acute respiratory syndrome coronavirus 2 / Complex / VIRAL PROTEIN

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