7vne › Citations

A non-ACE2 competing human single-domain antibody confers broad neutralization against SARS-CoV-2 and circulating variants.

Fig. 1
Fig. 2
Fig. 3
Yang Z, Wang Y, Jin Y, Zhu Y, Wu Y, Li C, Kong Y, Song W, Tian X, Zhan W, Huang A, Zhou S, Xia S, Tian X, Peng C, Chen C, Shi Y, Hu G, Du S, Wang Y, Xie Y, Jiang S, Lu L, Sun L, Song Y, Ying T
OpenAccess logo Signal Transduct Target Ther 6 378 (2021)
Related entries: 7vnb, 7vnc, 7vnd

Cited: 27 times
EuropePMC logo PMID: 34732694

Abstract

The current COVID-19 pandemic has heavily burdened the global public health system and may keep simmering for years. The frequent emergence of immune escape variants have spurred the search for prophylactic vaccines and therapeutic antibodies that confer broad protection against SARS-CoV-2 variants. Here we show that the bivalency of an affinity maturated fully human single-domain antibody (n3113.1-Fc) exhibits exquisite neutralizing potency against SARS-CoV-2 pseudovirus, and confers effective prophylactic and therapeutic protection against authentic SARS-CoV-2 in the host cell receptor angiotensin-converting enzyme 2 (ACE2) humanized mice. The crystal structure of n3113 in complex with the receptor-binding domain (RBD) of SARS-CoV-2, combined with the cryo-EM structures of n3113 and spike ecto-domain, reveals that n3113 binds to the side surface of up-state RBD with no competition with ACE2. The binding of n3113 to this novel epitope stabilizes spike in up-state conformations but inhibits SARS-CoV-2 S mediated membrane fusion, expanding our recognition of neutralization by antibodies against SARS-CoV-2. Binding assay and pseudovirus neutralization assay show no evasion of recently prevalent SARS-CoV-2 lineages, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) for n3113.1-Fc with Y58L mutation, demonstrating the potential of n3113.1-Fc (Y58L) as a promising candidate for clinical development to treat COVID-19.

Articles - 7vne mentioned but not cited (7)

  1. Omicron: A Heavily Mutated SARS-CoV-2 Variant Exhibits Stronger Binding to ACE2 and Potently Escapes Approved COVID-19 Therapeutic Antibodies. Shah M, Woo HG. Front Immunol 12 830527 (2021)
  2. Comprehensive structural analysis reveals broad-spectrum neutralizing antibodies against SARS-CoV-2 Omicron variants. Chi X, Xia L, Zhang G, Chi X, Huang B, Zhang Y, Chen Z, Han J, Wu L, Li Z, Sun H, Huang P, Yu C, Chen W, Zhou Q. Cell Discov 9 37 (2023)
  3. Nanobody-peptide-conjugate (NPC) for passive immunotherapy against SARS-CoV-2 variants of concern (VoC): a prospective pan-coronavirus therapeutics. Panda M, Kalita E, Singh S, Kumar K, Prajapati VK. Mol Divers 27 2577-2603 (2023)
  4. Biparatopic nanobodies targeting the receptor binding domain efficiently neutralize SARS-CoV-2. Pymm P, Redmond SJ, Dolezal O, Mordant F, Lopez E, Cooney JP, Davidson KC, Haycroft ER, Tan CW, Seneviratna R, Grimley SL, Purcell DFJ, Kent SJ, Wheatley AK, Wang LF, Leis A, Glukhova A, Pellegrini M, Chung AW, Subbarao K, Uldrich AP, Tham WH, Godfrey DI, Gherardin NA. iScience 25 105259 (2022)
  5. research-article Structural models of SARS-CoV-2 Omicron variant in complex with ACE2 receptor or antibodies suggest altered binding interfaces. Lubin JH, Markosian C, Balamurugan D, Pasqualini R, Arap W, Burley SK, Khare SD. bioRxiv 2021.12.12.472313 (2021)
  6. Modeling of ACE2 and antibodies bound to SARS-CoV-2 provides insights into infectivity and immune evasion. Lubin JH, Markosian C, Balamurugan D, Ma MT, Chen CH, Liu D, Pasqualini R, Arap W, Burley SK, Khare SD. JCI Insight 8 e168296 (2023)
  7. SARS-CoV-2 Omicron (BA.1 and BA.2) specific novel CD8+ and CD4+ T cell epitopes targeting spike protein. Parn S, Savsani K, Dakshanamurthy S. Immunoinformatics (Amst) 8 100020 (2022)


Reviews citing this publication (7)

  1. Broadly neutralizing antibodies to SARS-CoV-2 and other human coronaviruses. Chen Y, Zhao X, Zhou H, Zhu H, Jiang S, Wang P. Nat Rev Immunol 23 189-199 (2023)
  2. A structural view of the SARS-CoV-2 virus and its assembly. Hardenbrook NJ, Zhang P. Curr Opin Virol 52 123-134 (2022)
  3. Passive Immunotherapy Against SARS-CoV-2: From Plasma-Based Therapy to Single Potent Antibodies in the Race to Stay Ahead of the Variants. Strohl WR, Ku Z, An Z, Carroll SF, Keyt BA, Strohl LM. BioDrugs 36 231-323 (2022)
  4. Therapeutic applications of nanobodies against SARS-CoV-2 and other viral infections: Current update. Bhattacharya M, Chatterjee S, Lee SS, Chakraborty C. Int J Biol Macromol 229 70-80 (2023)
  5. Single-Domain Antibodies as Therapeutics for Respiratory RNA Virus Infections. Huang K, Ying T, Wu Y. Viruses 14 1162 (2022)
  6. Applications of nanobodies in the prevention, detection, and treatment of the evolving SARS-CoV-2. Wang W, Hu Y, Li B, Wang H, Shen J. Biochem Pharmacol 208 115401 (2023)
  7. Therapeutic nanobodies against SARS-CoV-2 and other pathogenic human coronaviruses. Yang Y, Li F, Du L. J Nanobiotechnology 22 304 (2024)

Articles citing this publication (13)



Quick links