Recombinant Protein Nanoparticles for Dual-Stage Inhibition of SARS-CoV‑2 Infection.

Area of Science:

• Biotechnology
• Nanotechnology
• Virology

Background:

• Recombinant proteins show potential as antiviral therapies.
• Developing effective nanotherapeutic platforms is crucial for targeted drug delivery.
• Understanding viral entry mechanisms is key to designing inhibitors.

Purpose of the Study:

• To engineer a self-assembling nanotherapeutic platform using recombinant proteins.
• To demonstrate the potential of this platform to inhibit multiple stages of viral infection using SARS-CoV-2 as a model.
• To create a bifunctional nanoparticle capable of blocking viral entry and fusion.

Main Methods:

• Genetically modifying oleosin, an amphiphilic plant-derived protein, to self-assemble into micellar nanoparticles.
• Engineering oleosin variants to present miniproteins that block ACE2 receptor binding and inhibit virus-cell membrane fusion.
• Evaluating the antiviral efficacy of the bifunctional nanoparticles against SARS-CoV-2.

Main Results:

• The engineered oleosin self-assembled into multivalent and bifunctional micellar nanoparticles.
• The nanoparticles potently inhibited SARS-CoV-2 infection with an IC50 of less than 8 nM.
• Bifunctional nanoparticles showed over a tenfold greater efficacy compared to monofunctional particles.

Conclusions:

• The developed nanotherapeutic platform demonstrates a promising strategy for creating potent antiviral agents.
• This approach utilizes solely recombinant techniques to develop single protein nanoparticles targeting multiple stages of viral infection.
• The study highlights the potential of self-assembling protein nanoparticles for next-generation antiviral therapeutics.