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TitleACE2-targeting monoclonal antibody as potent and broad-spectrum coronavirus blocker.
Journal, issue, pagesSignal Transduct Target Ther, Vol. 6, Issue 1, Page 315, Year 2021
Publish dateAug 25, 2021
AuthorsYuning Chen / Ya-Nan Zhang / Renhong Yan / Guifeng Wang / Yuanyuan Zhang / Zhe-Rui Zhang / Yaning Li / Jianxia Ou / Wendi Chu / Zhijuan Liang / Yongmei Wang / Yi-Li Chen / Ganjun Chen / Qi Wang / Qiang Zhou / Bo Zhang / Chunhe Wang /
PubMed AbstractThe evolution of coronaviruses, such as SARS-CoV-2, makes broad-spectrum coronavirus preventional or therapeutical strategies highly sought after. Here we report a human angiotensin-converting enzyme ...The evolution of coronaviruses, such as SARS-CoV-2, makes broad-spectrum coronavirus preventional or therapeutical strategies highly sought after. Here we report a human angiotensin-converting enzyme 2 (ACE2)-targeting monoclonal antibody, 3E8, blocked the S1-subunits and pseudo-typed virus constructs from multiple coronaviruses including SARS-CoV-2, SARS-CoV-2 mutant variants (SARS-CoV-2-D614G, B.1.1.7, B.1.351, B.1.617.1, and P.1), SARS-CoV and HCoV-NL63, without markedly affecting the physiological activities of ACE2 or causing severe toxicity in ACE2 "knock-in" mice. 3E8 also blocked live SARS-CoV-2 infection in vitro and in a prophylactic mouse model of COVID-19. Cryo-EM and "alanine walk" studies revealed the key binding residues on ACE2 interacting with the CDR3 domain of 3E8 heavy chain. Although full evaluation of safety in non-human primates is necessary before clinical development of 3E8, we provided a potentially potent and "broad-spectrum" management strategy against all coronaviruses that utilize ACE2 as entry receptors and disclosed an anti-coronavirus epitope on human ACE2.
External linksSignal Transduct Target Ther / PubMed:34433803 / PubMed Central
MethodsEM (single particle)
Resolution3.2 - 3.4 Å
Structure data

31732

7v61

EMDB-31732, PDB-7v61:
ACE2 -Targeting Monoclonal Antibody as Potent and Broad-Spectrum Coronavirus Blocker
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-31733: cryo-EM map focused on interface between 3E8 and ACE2
Method: EM (single particle) / Resolution: 3.4 Å

Chemicals

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

ChemComp-ZN:
Unknown entry

ChemComp-HOH:
WATER / Water

Source
  • homo sapiens (human)
  • severe acute respiratory syndrome coronavirus 2
KeywordsMEMBRANE PROTEIN / ACE2-B0AT1 complex

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