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Acetate-encapsulated Linolenic Acid Liposomes Reduce SARS-CoV-2 and RSV Infection
Andrew R McGill1,2,3, Eleni Markoutsa1,2,4, Karthick Mayilsamy1,3
1James A. Haley Veterans Hospital, Tampa, FL 33612, USA.
Abstract:
Emergent Coronaviridae viruses, such as SARS-CoV-1 in 2003, MERS-CoV in 2012, and SARS-CoV-2 (CoV-2) in 2019, have caused millions of deaths. These viruses have added to the existing respiratory infection burden along with respiratory syncytial virus (RSV) and influenza. There are limited therapies for respiratory viruses, with broad-spectrum treatment remaining an unmet need. Since gut fermentation of fiber produces short-chain fatty acids (SCFA) with antiviral potential, developing a fatty acid-based broad-spectrum antiviral was investigated. Molecular docking of fatty acids showed α-linolenic acid (ALA) is likely to interact with CoV-2-S, NL63-CoV-S, and RSV-F, and an ALA-containing liposome interacted with CoV-2 directly, degrading the particle. Furthermore, a combination of ALA and a SCFA-acetate synergistically inhibited CoV2-N expression and significantly reduced viral plaque formation and IL-6 and IL-1β transcript expression in Calu-3 cells, while increasing the expression of IFN-β. A similar effect was also observed in RSV-infected A549 cells. Moreover, mice infected with a murine-adapted SARS-CoV-2 (MA10) and treated with an ALA-liposome encapsulating acetate showed significant reductions in plaque-forming units present in lung tissue and in infection-associated lung inflammation and cytokines. Taken together, these results demonstrate that the ALA liposome-encapsulating acetate can be a promising broad antiviral therapy against respiratory infections.
Insights
A novel fatty acid therapy shows promise against respiratory viruses like SARS-CoV-2 and RSV. This broad-spectrum antiviral approach, using alpha-linolenic acid (ALA) liposomes with acetate, effectively reduced viral load and inflammation in cell and animal models.
Area of Science:
- Virology
- Drug Discovery
- Immunology
Background:
- Emergent coronaviruses (SARS-CoV, MERS-CoV, SARS-CoV-2) and other respiratory viruses (RSV, influenza) pose significant global health threats.
- Limited broad-spectrum antiviral therapies are available for respiratory infections, highlighting an unmet clinical need.
- Short-chain fatty acids (SCFAs) produced from fiber fermentation possess antiviral properties.
Purpose of the Study:
- To investigate the potential of fatty acids as broad-spectrum antiviral agents against respiratory viruses.
- To evaluate alpha-linolenic acid (ALA) and its liposomal formulation, combined with acetate, for antiviral activity.
Main Methods:
- Molecular docking was used to identify fatty acids with potential interactions with viral proteins (CoV-2-S, NL63-CoV-S, RSV-F).
- In vitro studies involved treating infected Calu-3 and A549 cells with ALA-liposomes and acetate, assessing viral gene expression and plaque formation.
- In vivo studies utilized a murine model of SARS-CoV-2 infection treated with ALA-liposomes encapsulating acetate, evaluating viral load and lung inflammation.
Main Results:
- Molecular docking predicted ALA interaction with key viral surface proteins.
- ALA-liposomes directly interacted with SARS-CoV-2 particles, leading to degradation.
- Combined ALA and acetate synergistically reduced viral replication markers (CoV2-N expression, plaque formation) and modulated inflammatory responses (IL-6, IL-1β, IFN-β) in cell cultures.
- In vivo treatment significantly decreased viral load and lung inflammation in infected mice.
Conclusions:
- ALA liposomes encapsulating acetate demonstrate potent broad-spectrum antiviral activity against SARS-CoV-2 and RSV.
- This formulation represents a promising therapeutic strategy for managing respiratory viral infections.
- Further development of this fatty acid-based therapy could address the need for effective broad-spectrum antivirals.
