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bioRxiv · 10.1101/2022.04.09.487739

Disrupting ACE2 Dimerization Mitigates the Infection by SARS-COV-2

Zhu, J.·Su, Y.·Tang, Y.
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Abstract

The coronavirus disease 2019 (COVID-19) pandemic has caused over 6 million death and 460 million reported cases globally. More effective antiviral medications are needed to curb the continued spread of this disease. The infection by SARS-COV-2 virus is initiated via the interaction between the receptor binding domain (RBD) of the viral glycoprotein Spike (S protein) and the N-term peptidase domain (PD) of the angiotensin-converting enzyme 2 (ACE2) expressed on host cell membrane. ACE2 forms protein homodimer primarily through its ferredoxin-like fold domain (aka. Neck-domain). We investigated whether the dimerization of ACE2 receptor plays a role in SARS-COV-2 virus infection. We report here that the ACE2 receptor dimerization enhances the recognition of SARS-COV-2 S protein. A 43 amino acid peptide based on the N-term of Neck-domain could block the ACE2 dimerization and the interaction between RBD and ACE2, and mitigate the SARS-COV-2/host cell interaction. Our study illustrated a new route to develop potential therapeutics for the prevention and treatment of SARS-COV-2 viral infection.

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Zhu, J., Su, Y., Tang, Y.. 2022-04-11. Disrupting ACE2 Dimerization Mitigates the Infection by SARS-COV-2. https://doi.org/10.1101/2022.04.09.487739

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