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TitleBroadly neutralizing and protective nanobodies against SARS-CoV-2 Omicron subvariants BA.1, BA.2, and BA.4/5 and diverse sarbecoviruses.
Journal, issue, pagesNat Commun, Vol. 13, Issue 1, Page 7957, Year 2022
Publish dateDec 27, 2022
AuthorsMingxi Li / Yifei Ren / Zhen Qin Aw / Bo Chen / Ziqing Yang / Yuqing Lei / Lin Cheng / Qingtai Liang / Junxian Hong / Yiling Yang / Jing Chen / Yi Hao Wong / Jing Wei / Sisi Shan / Senyan Zhang / Jiwan Ge / Ruoke Wang / Jay Zengjun Dong / Yuxing Chen / Xuanling Shi / Qi Zhang / Zheng Zhang / Justin Jang Hann Chu / Xinquan Wang / Linqi Zhang /
PubMed AbstractAs SARS-CoV-2 Omicron and other variants of concern (VOCs) continue spreading worldwide, development of antibodies and vaccines to confer broad and protective activity is a global priority. Here, we ...As SARS-CoV-2 Omicron and other variants of concern (VOCs) continue spreading worldwide, development of antibodies and vaccines to confer broad and protective activity is a global priority. Here, we report on the identification of a special group of nanobodies from immunized alpaca with potency against diverse VOCs including Omicron subvariants BA.1, BA.2 and BA.4/5, SARS-CoV-1, and major sarbecoviruses. Crystal structure analysis of one representative nanobody, 3-2A2-4, discovers a highly conserved epitope located between the cryptic and the outer face of the receptor binding domain (RBD), distinctive from the receptor ACE2 binding site. Cryo-EM and biochemical evaluation reveal that 3-2A2-4 interferes structural alteration of RBD required for ACE2 binding. Passive delivery of 3-2A2-4 protects K18-hACE2 mice from infection of authentic SARS-CoV-2 Delta and Omicron. Identification of these unique nanobodies will inform the development of next generation antibody therapies and design of pan-sarbecovirus vaccines.
External linksNat Commun / PubMed:36575191 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.8 - 3.29 Å
Structure data

EMDB-33923: Cryo-EM structure of SARS-CoV-2 Omicron spike glycoprotein in complex with three neutralizing nanobody 3-2A2-4
Method: EM (single particle) / Resolution: 3.29 Å

PDB-7x2j:
Crystal structure of nanobody Nb70 with SARS-CoV RBD
Method: X-RAY DIFFRACTION / Resolution: 2.4 Å

PDB-7x2k:
Crystal structure of nanobody Nb70 with antibody 1F11 fab and SARS-CoV-2 RBD
Method: X-RAY DIFFRACTION / Resolution: 2.4 Å

PDB-7x2l:
Crystal structure of nanobody 3-2A2-4 with SARS-CoV-2 RBD
Method: X-RAY DIFFRACTION / Resolution: 2.4 Å

PDB-7x2m:
Crystal structure of nanobody 1-2C7 with SARS-CoV-2 RBD
Method: X-RAY DIFFRACTION / Resolution: 1.8 Å

Chemicals

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

ChemComp-HOH:
WATER / Water

Source
  • severe acute respiratory syndrome coronavirus 2
  • vicugna pacos (alpaca)
  • severe acute respiratory syndrome-related coronavirus
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV / nanobody / spike / receptor binding domain / VIRAL PROTEIN-IMMUNE SYSTEM complex / SARS-CoV-2

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