Dauricine interferes with SARS-CoV-2 variants infection by blocking the interface between RBD and ACE2

Area of Science:

• Virology
• Drug Discovery
• Computational Chemistry

Background:

• Emerging SARS-CoV-2 variants like Delta and Omicron pose global health risks due to partial resistance to existing vaccines and antivirals.
• Developing novel antiviral strategies is crucial to combat evolving viral threats.

Purpose of the Study:

• To identify potential antiviral agents targeting the interaction between SARS-CoV-2 spike proteins and the human ACE2 receptor.
• To investigate the evolutionary trends of SARS-CoV-2 variants concerning spike protein-ACE2 interactions.

Main Methods:

• Virtual screening of Traditional Chinese medicine (TCM) monomers against the ACE2-receptor binding domain (RBD) interface.
• Live-virus neutralization assays to determine antiviral activity.
• Computational analysis of drug-target interactions.

Main Results:

• Virtual screening identified nine potential TCM monomers targeting the ACE2-RBD binding interface.
• Dauricine demonstrated significant antiviral activity against SARS-CoV-2 (original, Delta, Omicron) with IC50 values ranging from 18.2 to 33.3 μM.
• Computational studies revealed Dauricine's adherence to the RBD via π-π and electrostatic interactions.

Conclusions:

• Dauricine is a promising candidate for targeting viral entry and combating SARS-CoV-2 variants.
• This discovery supports the development of new variant-specific drugs and enhances preparedness for future viral outbreaks.