Inhibition of SARS-CoV-2 Spike Protein Pseudotyped Virus Infection Using ACE2-Tethered Micro/Nanoparticles.

Area of Science:

• Biotechnology
• Virology
• Nanomedicine

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, necessitating new therapeutic strategies.
• The virus uses the angiotensin-converting enzyme 2 (ACE2) receptor for host cell entry.
• Viral mutations drive the need for effective countermeasures against evolving SARS-CoV-2 strains.

Purpose of the Study:

• To develop and evaluate ACE2-functionalized micro/nanoparticles as a decoy strategy against SARS-CoV-2 infection.
• To investigate the efficacy of immobilized ACE2 on particles in blocking viral entry compared to soluble ACE2.

Main Methods:

• ACE2-streptavidin fusion proteins were produced using recombinant DNA technology.
• Proteins were anchored onto biotinylated fluorescent polystyrene micro/nanoparticles (0.15–5 µm).
• The ability of ACE2-tethered particles to inhibit pseudotyped lentivirus entry into ACE2-expressing cells was assessed.

Main Results:

• ACE2-tethered micro/nanoparticles successfully prevented viral entry into target cells.
• Micro-sized particles (2 and 5 µm) demonstrated superior inhibition of viral attachment and entry compared to soluble ACE2.
• Functionalized particles acted as effective decoys, blocking infection by SARS-CoV-2 strains.

Conclusions:

• ACE2-functionalized micro/nanoparticles represent a viable decoy strategy to neutralize SARS-CoV-2.
• Particle-based decoys offer enhanced efficacy over soluble forms in blocking viral infection.
• This approach holds potential for developing novel prophylactic and therapeutic interventions against COVID-19.