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TitleDiscovery of Nanosota-2, -3, and -4 as super potent and broad-spectrum therapeutic nanobody candidates against COVID-19.
Journal, issue, pagesJ Virol, Vol. 97, Issue 11, Page e0144823, Year 2023
Publish dateNov 30, 2023
AuthorsGang Ye / Ruangang Pan / Fan Bu / Jian Zheng / Alise Mendoza / Wei Wen / Lanying Du / Benjamin Spiller / Brian E Wadzinski / Bin Liu / Stanley Perlman / Fang Li /
PubMed AbstractThe COVID-19 pandemic exposed limitations of conventional antibodies as therapeutics, including high cost, limited potency, ineffectiveness against new viral variants, and primary reliance on ...The COVID-19 pandemic exposed limitations of conventional antibodies as therapeutics, including high cost, limited potency, ineffectiveness against new viral variants, and primary reliance on injection-only delivery. Nanobodies are single-domain antibodies with therapeutic potentials. We discovered three anti-SARS-CoV-2 nanobodies, named Nanosota-2, -3, and -4, from an immunized alpaca. Nanosota-2 is super potent against prototypic SARS-CoV-2, Nanosota-3 is highly potent against the omicron variant, and Nanosota-4 is effective against both SARS-CoV-1 and SARS-CoV-2. In addition to their super potency and combined broad antiviral spectrum, these nanobodies are cost-effective, can be easily adapted to new viral variants through phage display, and can potentially be administered as inhalers. The Nanosota series are powerful therapeutic candidates to combat circulating SARS-CoV-2 and prepare for possible future coronavirus pandemics.
External linksJ Virol / PubMed:37855638 / PubMed Central
MethodsEM (single particle)
Resolution2.5 - 5.6 Å
Structure data

EMDB-29794, PDB-8g72:
SARS-CoV-2 spike/Nb2 complex with 1 RBD up (local refinement at 5.6 A)
Method: EM (single particle) / Resolution: 5.6 Å

EMDB-29795, PDB-8g73:
SARS-CoV-2 spike/Nb3 complex with 2 RBDs up and 3 Nb3 bound at 2.5 A
Method: EM (single particle) / Resolution: 2.5 Å

EMDB-29796, PDB-8g74:
SARS-CoV-2 spike/Nb3 complex with 1 RBD up and 2 Nb3
Method: EM (single particle) / Resolution: 2.5 Å

EMDB-29797, PDB-8g75:
SARS-CoV-2 spike/Nb4 complex with 2 RBDs up and 3 Nb4 bound
Method: EM (single particle) / Resolution: 3.4 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • severe acute respiratory syndrome coronavirus 2
  • vicugna pacos (alpaca)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2 / VIRAL PROTEIN-IMMUNE SYSTEM complex / Nanobody

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