Customizably designed multibodies neutralize SARS-CoV-2 in a variant-insensitive manner

Area of Science:

• Virology
• Immunology
• Biotechnology

Background:

• The COVID-19 pandemic necessitates continuous development of countermeasures against SARS-CoV-2 variants.
• Existing therapeutic strategies face challenges due to the rapid evolution of the virus.

Purpose of the Study:

• To engineer a versatile molecular scaffold capable of neutralizing diverse SARS-CoV-2 variants.
• To evaluate the efficacy of this scaffold as a potential therapeutic agent and diagnostic tool.

Main Methods:

• Design and construction of a pentameric scaffold with customizable protein binding modules.
• Assessment of the scaffold's ability to bind and neutralize SARS-CoV-2 Spike proteins.
• In vitro testing of the scaffold's efficacy in blocking viral cell attachment and entry.
• Evaluation of antiviral activity against multiple SARS-CoV-2 variants at low concentrations.

Main Results:

• The pentameric scaffold effectively neutralizes SARS-CoV-2 Spike proteins from multiple viral particles simultaneously.
• A construct utilizing two modules targeting the Spike RBD domain outperformed human antibodies in vitro.
• The scaffold demonstrated potent inhibition of viral replication at picomolar concentrations, irrespective of the variant.
• The multibody showed effectiveness against SARS-CoV-2 variants, blocking cell attachment and pseudotyped virus entry.

Conclusions:

• The customizable pentameric scaffold represents a promising platform for developing therapeutics and detection devices against SARS-CoV-2.
• This adaptable molecular tool enhances preparedness for rapidly evolving viral threats.
• The scaffold's ease of production in procaryotic systems facilitates its potential for widespread application.