Chitosan-Based Antiviral Shows Potential Against Respiratory Viruses

A collaboration between various centers of the Spanish National Research Council (CSIC) has led to the development of an innovative broad-spectrum antiviral based on a natural substance found in the shells of crustaceans. The compound, derived from chitosan—a material derived from chitin, abundant in the exoskeleton of crabs and shrimp—has been shown to be effective against respiratory viruses such as SARS-CoV-2 and respiratory syncytial virus (RSV) and could be administered via aerosols or inhalers even after infection.

The work, recently published in the journal Communications Biology, is the result of a multidisciplinary collaboration between the Institute of Integrative Systems Biology (I2SysBio, CSIC-UV), the Institute of General Organic Chemistry (IQOG-CSIC), the National Institute of Agricultural and Food Research and Technology (INIA-CSIC), the Institute of Biomedicine of Valencia (IBV-CSIC), the Center for Biomedical Network Research in Rare Diseases (CIBERER) and the Center for Cooperative Research in Biomaterials (CIC biomaGUNE).

Decoy to block the entry of the virus

“The compound was designed in our laboratory using heparan sulfates as a reference, sulfated polysaccharides used by many viruses to adhere to cell surfaces during the infectious process,” explains Alfonso Fernández-Mayoralas, a researcher at IQOG-CSIC. “Our polysaccharides act as decoys: they bind to viruses and prevent them from coming into contact with epithelial cells, thereby blocking infection,” adds his colleague Julia Revuelta.

“The compound was designed in our laboratory using heparan sulfates as a reference, sulfated polysaccharides used by many viruses to adhere to the cell surface during the infectious process.” Alfonso Fernández-Mayoralas, researcher at IQOG-CSIC

The antiviral agent acts irreversibly and has demonstrated potent activity in cellular and animal models against different SARS-CoV-2 variants, as well as against strains of RSV, a virus that particularly affects young children and the elderly. In mouse models, administration of the compound before infection reduced viral load by more than six orders of magnitude. Notably, significant therapeutic efficacy was also observed when administered after the onset of infection.

Efficacy in cell cultures and animal models

“The most promising compound blocked viral entry into both cell cultures and infected mice, even when applied after the infection had already begun ,” explains Ron Geller, a researcher at I2SysBio. “These results are very promising and point to the compound’s potential as an effective antiviral treatment,” agrees Miguel A. Martín Acebes, from INIA-CSIC, who is responsible for the efficacy trials in animal models.

From the point of view of the mechanism of action, the antiviral binds directly to the virus, preventing its attachment to cellular receptors.

From a mechanism of action perspective, the antiviral binds directly to the virus, preventing it from attaching to cellular receptors. “It works early in the infection cycle, before the virus can penetrate cells, preventing its multiplication,” Geller explained.

“Furthermore, by acting on a pathway common to multiple viruses, its spectrum of action is broader than that of specific antivirals.” One of the study’s most relevant findings is the compound’s ability to function both prophylactically and therapeutically, opening the door to its clinical use in the early stages of respiratory viral infections.

Security and tolerance

Safety studies conducted in animals showed no toxic effects after repeated intranasal administration, suggesting a good tolerance profile. “One of the most interesting aspects is that it can be used repeatedly and is still eliminated from the body within about 48 hours,” emphasized Julia Revuelta and Alfonso Fernández-Mayoralas.

“One of the most interesting aspects is that it can be used repeatedly, and yet it is eliminated from the body in about 48 hours.” Alfonso Fernández-Mayoralas, researcher at IQOG-CSIC

To achieve this, the IQOG team carried out a chemical modification that allowed them to introduce a radioisotope and conduct biodistribution studies in collaboration with Jordi Llop’s laboratory at CIC biomaGUNE. The data confirmed that the drug does not accumulate in the body, reinforcing its potential for safe use in repeatedly administered formulations, such as inhalers or nasal sprays.

Usefulness of the broad-spectrum antiviral against future pandemics

One of the compound’s major advantages is its ease of production. Chitosan is a natural polymer widely used in the biomedical and food industries, making it widely available and cost-effective . This would allow for large-scale production without logistical difficulties, making it an attractive candidate for the development of preventive and therapeutic formulations.

“Having broad-spectrum antivirals that can be administered nasally at the first sign of symptoms would make a difference in containing and managing many respiratory infections,” said Julia Revuelta, researcher at IQOG-CSIC

This breakthrough represents an innovative strategy for addressing emerging or re-emerging respiratory diseases. In addition to its potential for COVID-19 and RSV, the new antiviral could offer protection against future viruses with similar entry mechanisms, providing a flexible and rapid tool against new pandemics.

“Having broad-spectrum antivirals that can be administered nasally from the first symptoms would make a difference in containing and managing many respiratory infections,” the researchers concluded.

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(Featured image by CDC via Unsplash)

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First published in GACETA MEDICA. A third-party contributor translated and adapted the article from the original. In case of discrepancy, the original will prevail.

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