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Updated: Jun 24, 2026
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Procedures for the Identification of SARS-CoV-2 Entry Inhibitors as Potential Antivirals using MLV-Based Pseudoviruses
Published on: February 27, 2026
Allosteric Targeting of the ACE2 Dimer Interface by a Medium-sized Compound Inhibits SARS-CoV-2 Entry
Mariko Yokogawa1, Shunki Kaneichi1, Mahoro Horiuchi1
1Faculty of Pharmacy, Division of Physics for Life Functions, Keio University, Tokyo 105-8512, Japan.
Journal of Molecular Biology
|June 22, 2026
Summary
Researchers discovered a new way to inhibit SARS-CoV-2 (the virus that causes COVID-19) by targeting the ACE2 protein. A novel compound binds to ACE2, altering its shape to block viral entry and suppress infection.
Area of Science:
- Biochemistry
- Virology
- Drug Discovery
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the ACE2 receptor for host cell entry.
- Existing treatments do not directly inhibit the spike protein-ACE2 interaction.
Purpose of the Study:
- To discover novel inhibitors of SARS-CoV-2 entry by targeting the ACE2 receptor.
- To identify compounds that disrupt the interaction between the SARS-CoV-2 spike protein and ACE2.
Main Methods:
- Artificial intelligence-guided virtual screening of medium-sized compounds.
- Nuclear magnetic resonance (NMR) spectroscopy to determine compound binding.
- Infection assays and docking simulations using ACE2 mutants.
Main Results:
- A novel compound was identified that suppresses SARS-CoV-2 infection by binding to ACE2.
- The compound binds to a region near the ACE2 dimer interface, distinct from the viral binding site.
- Compound binding appears to stabilize a looser ACE2 dimer conformation, hindering viral entry.
Conclusions:
- A previously unknown allosteric regulatory site on ACE2 was identified.
- Medium-sized molecules targeting this site can modulate ACE2 conformation to inhibit SARS-CoV-2 infection.
- This discovery opens new avenues for developing COVID-19 therapeutics.
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