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TitleA broad neutralizing nanobody against SARS-CoV-2 engineered from an approved drug.
Journal, issue, pagesCell Death Dis, Vol. 15, Issue 6, Page 458, Year 2024
Publish dateJun 28, 2024
AuthorsQianyun Liu / Yuchi Lu / Chenguang Cai / Yanyan Huang / Li Zhou / Yanbin Guan / Shiying Fu / Youyou Lin / Huan Yan / Zhen Zhang / Xiang Li / Xiuna Yang / Haitao Yang / Hangtian Guo / Ke Lan / Yu Chen / Shin-Chen Hou / Yi Xiong /
PubMed AbstractSARS-CoV-2 infection is initiated by Spike glycoprotein binding to the human angiotensin-converting enzyme 2 (ACE2) receptor via its receptor binding domain. Blocking this interaction has been proven ...SARS-CoV-2 infection is initiated by Spike glycoprotein binding to the human angiotensin-converting enzyme 2 (ACE2) receptor via its receptor binding domain. Blocking this interaction has been proven to be an effective approach to inhibit virus infection. Here we report the discovery of a neutralizing nanobody named VHH60, which was directly produced from an engineering nanobody library based on a commercialized nanobody within a very short period. VHH60 competes with human ACE2 to bind the receptor binding domain of the Spike protein at S, Sand S as determined by structural analysis, with an affinity of 2.56 nM. It inhibits infections of both ancestral SARS-CoV-2 strain and pseudotyped viruses harboring SARS-CoV-2 wildtype, key mutations or variants at the nanomolar level. Furthermore, VHH60 suppressed SARS-CoV-2 infection and propagation 50-fold better and protected mice from death for twice as long as the control group after SARS-CoV-2 nasal infections in vivo. Therefore, VHH60 is not only a powerful nanobody with a promising profile for disease control but also provides evidence for a highly effective and rapid approach to generating therapeutic nanobodies.
External linksCell Death Dis / PubMed:38937437 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution3.2 - 3.4 Å
Structure data

38418
EMDB entry, No image

8xki

EMDB-38418, PDB-8xki:
A neutralizing nanobody VHH60 against wt SARS-CoV-2
Method: EM (single particle) / Resolution: 3.2 Å

PDB-8xk2:
A neutralizing nanobody VHH60 against wt SARS-CoV-2
Method: X-RAY DIFFRACTION / Resolution: 3.4 Å

Chemicals

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

Source
  • severe acute respiratory syndrome coronavirus 2
  • synthetic construct (others)
KeywordsANTIVIRAL PROTEIN/IMMUNE SYSTEM / COVID-19 / spike glycoprotein / virus / antibody / VIRAL PROTEIN/IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM complex / ANTIVIRAL PROTEIN / ANTIVIRAL PROTEIN-IMMUNE SYSTEM complex

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