Anti-human ACE2 antibody neutralizes and inhibits virus production of SARS-CoV-2 variants of concern

Abigael E. Chaouat, Ilija Brizic, Paola Kucan Brlic, Nofar Atari, Limor Kliker, Or Alfi, Michal Mandelboim, Dana Wolf, Laith Tafish, Inbal Kol, Stipan Jonjic, Ofer Mandelboim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The global pandemic caused by SARS-CoV-2 is a major public health problem. Virus entry occurs via binding to ACE2. Five SARS-CoV-2 variants of concern (VOCs) were reported so far, all having immune escape characteristics. Infection with the current VOC Omicron was noticed in immunized and recovered individuals; therefore, the development of new treatments against VOC infections is urgently needed. Most approved mAbs treatments against SARS-CoV-2 are directed against the spike protein of the original virus and are therefore inefficient against Omicron. Here, we report on the generation of hACE2.16, an anti-ACE2 antibody that recognizes and blocks ACE2-RBD binding without affecting ACE2 enzymatic activity. We demonstrate that hACE2.16 binding to ACE2 does not affect its surface expression and that hACE2.16 blocks infection and virus production of various VOCs including Omicron BA.1 and BA.2. hACE2.16 might, therefore, be an efficient treatment against all VOCs, the current and probably also future ones.

Original languageEnglish
Article number104935
JournaliScience
Volume25
Issue number9
DOIs
StatePublished - 16 Sep 2022

Funding

FundersFunder number
ISF Israel-China2554/18
Integra Holdings LTD
Israel Innovation Authority Kamin62615
Israel Science Foundation Moked442-18
MOST-DKFZ
Rothschild Foundation
Israel Cancer Research Fund
German-Israeli Foundation for Scientific Research and Development1412-414.13/2017
Ministry of Science, Technology and Space3-14931
Hebrew University of Jerusalem
Ministry of Science and Technology, Israel3-14764

    Keywords

    • Health sciences
    • immune response
    • immunology
    • virology

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