"Molecular Masks" for ACE2 to Effectively and Safely Block SARS-CoV-2 Virus Entry

Area of Science:

• Biochemistry
• Virology
• Drug Discovery

Background:

• Coronavirus Disease 2019 (COVID-19) is a global health crisis caused by SARS-CoV-2.
• The virus enters cells by binding its spike protein to the ACE2 receptor.

Purpose of the Study:

• To identify compounds that inhibit SARS-CoV-2 entry.
• To develop and test novel peptoid derivatives targeting the spike protein-ACE2 interaction.

Main Methods:

• Utilized unique cell screening technology to identify ACE2-binding peptoids.
• Developed dimeric peptoid derivatives (ACE2P1D1, ACE2P2D1).
• Tested inhibition of SARS-CoV-2 and D614G mutant pseudovirus entry.

Main Results:

• Identified two peptoid compounds and developed dimeric derivatives ACE2P1D1 and ACE2P2D1.
• ACE2P1D1 and ACE2P2D1 effectively blocked spike protein-ACE2 interaction and SARS-CoV-2 pseudovirus entry.
• Compounds inhibited entry of a D614G mutant pseudovirus.
• No decrease in ACE2 expression or enzyme activity was observed.

Conclusions:

• Dimeric peptoid derivatives ACE2P1D1 and ACE2P2D1 are potent inhibitors of SARS-CoV-2 entry.
• These compounds demonstrate potential for safe therapeutic application due to preserved ACE2 function.