Engineering an ACE2-Derived Fragment as a Decoy for Novel SARS-CoV-2 Virus

Fabiana Renzi, Austin Seamann, Koelina Ganguly, Kabita Pandey, Siddappa N. Byrareddy, Surinder Batra, Sushil Kumar, Dario Ghersi

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Entry inhibitors are an important resource in the response against emerging pathogens like the novel SARS-CoV-2, which enters human cells via interaction between the surface spike glycoprotein and the cellular membrane receptor angiotensin-converting enzyme 2 (ACE2). Using a combination of comparative structural analyses of the binding surface of the spike to ACE2, docking experiments, and molecular dynamics simulations, we identified a stable fragment of ACE2 that binds to the spike, is soluble, and is not predicted to bind to its physiological ligand angiotensin II. From this fragment we computationally designed and experimentally validated a smaller, stable peptide that disrupts ACE2-spike interaction at nanomolar concentrations, suggesting its potential use as a decoy that could interfere with viral binding by competition.

Original languageEnglish (US)
Pages (from-to)857-867
Number of pages11
JournalACS Pharmacology and Translational Science
Volume6
Issue number6
DOIs
StatePublished - Jun 9 2023

Keywords

  • ACE2
  • SARS-CoV-2
  • decoy
  • entry inhibitors
  • spike

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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