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Production of a SARS-CoV-2 Virus-Like-Particle System to Investigate Viral Life Cycles In Vitro

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Lipid Nanoparticle-Based Inhibitors for SARS-CoV-2 Host Cell Infection.

Vinith Yathindranath^1,2, Nura Safa^1,2, Mateusz Marek Tomczyk^1,3

¹Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, MB, Canada.

International Journal of Nanomedicine

|April 2, 2024

Summary

New lipid nanoparticles (LNPs) show promise for treating SARS-CoV-2. These LNP-Trap and LNP-Trim formulations safely inhibit viral entry in airway cells, offering a localized approach for upper airway infections.

Keywords:

SARS-CoV-2 antiviral gene knockdown intranasal drug delivery lipid nanoparticles

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Published on: January 20, 2023

Area of Science:

Biotechnology
Virology
Nanomedicine

Background:

The COVID-19 pandemic necessitates novel therapeutic strategies against SARS-CoV-2.
Targeting viral entry mechanisms in the upper airway is crucial for controlling infection.

Purpose of the Study:

To develop and evaluate lipid nanoparticle (LNP) formulations as inhibitors of SARS-CoV-2 entry.
To reduce viral infection in the nose and upper airway using localized LNP treatments.

Main Methods:

Two LNP formulations, LNP-Trap and LNP-Trim, were synthesized using microfluidic mixing.
LNP-Trap utilized spike protein binding ligands; LNP-Trim encapsulated ACE2 or TMPRSS2 siRNAs.
Biocompatibility, cell uptake, pseudovirus neutralization, and in vivo biodistribution were assessed.

Main Results:

Both LNP formulations demonstrated biocompatibility in Calu-3 airway epithelial cells.
LNP-Trap inhibited pseudovirus infection by 90%; LNP-Trim reduced ACE2/TMPRSS2 by 50-70% and inhibited infection by over 90%.
In vivo studies showed nasal retention of LNPs with minimal systemic exposure.

Conclusions:

LNP-Trap and LNP-Trim formulations effectively and safely inhibit SARS-CoV-2 pseudoviral infection in airway cells.
These findings support the potential of localized LNP-based treatments for upper airway SARS-CoV-2 infections.