Development of Broad-Spectrum β-Cyclodextrins-Based Nanomaterials Against Influenza Viruses.

Area of Science:

• Virology
• Nanotechnology
• Drug Discovery

Background:

• Viral epidemics and pandemics, particularly influenza, pose significant public health threats.
• Current antiviral strategies face challenges with resistance and limited spectrum.
• Influenza and SARS-CoV-2 viruses utilize sialic acid for host cell attachment.

Purpose of the Study:

• To engineer and evaluate a novel broad-spectrum antiviral agent targeting sialic acid-dependent viruses.
• To assess the efficacy, mechanism of action, and resistance profile of the engineered macromolecule (CD-SA).
• To compare the antiviral potential of CD-SA against influenza and SARS-CoV-2 with existing treatments.

Main Methods:

• Macromolecules (CD-SA) were synthesized by modifying a β-cyclodextrin scaffold with sialic acid epitopes.
• Antiviral activity was tested in vitro, ex vivo (human airway epithelia), and in vivo (mouse models).
• Mechanism of action, virucidal effects, and genetic barrier to resistance (with and without interferon-λ1) were evaluated.

Main Results:

• CD-SA demonstrated potent virucidal antiviral activity against human influenza A and B viruses.
• Antiviral activity was also observed against SARS-CoV-2, highlighting its broad-spectrum potential.
• CD-SA showed superior efficacy compared to Oseltamivir in mouse models and exhibited a higher genetic barrier to resistance when combined with interferon-λ1.

Conclusions:

• The engineered β-cyclodextrin-based nanomaterial (CD-SA) is a promising therapeutic candidate for influenza infections.
• CD-SA exhibits broad-spectrum activity against sialic acid-dependent viruses, including SARS-CoV-2.
• This novel antiviral strategy warrants further investigation for clinical application in managing viral respiratory diseases.