An ACE2-Based Decoy Inhibitor Effectively Neutralizes SARS-CoV-2 Omicron BA.5 Variant

Area of Science:

• Virology
• Drug Discovery

Background:

• The SARS-CoV-2 Omicron BA.5 sublineage exhibits increased transmissibility and immune evasion.
• Existing monoclonal antibodies show reduced efficacy against BA.5, necessitating novel therapeutics.
• Kansetin, previously identified as an ACE2 mimetic and SARS-CoV-2 antagonist, demonstrated broad neutralization against earlier variants.

Purpose of the Study:

• To evaluate the efficacy of Kansetin against the SARS-CoV-2 Omicron BA.5 variant.
• To confirm the hypothesis that Kansetin's ACE2-mimicking property retains neutralization activity against BA.5.

Main Methods:

• Surface Plasmon Resonance (SPR) was used to assess Kansetin-Spike binding affinity.
• Pseudovirus and live virus assays were employed to determine cell infection inhibition.
• In vitro studies were conducted to measure dissociation constant (KD) and half maximal inhibitory concentration (IC50).

Main Results:

• Kansetin demonstrated nanomolar to picomolar level binding affinity (KD) and inhibitory concentration (IC50) against the BA.5 sublineage.
• The compound exhibited competent inhibition of cell infection mediated by the BA.5 variant.
• SPR and cell-based assays confirmed Kansetin's potent antiviral activity.

Conclusions:

• Kansetin is a promising therapeutic candidate for treating infections caused by the SARS-CoV-2 Omicron BA.5 variant.
• Its ACE2-mimicking mechanism suggests potential efficacy against future SARS-CoV-2 sublineages.
• Kansetin offers a potential broad-spectrum therapeutic strategy against evolving coronaviruses.