I2SysBio scientists develop a broad-spectrum antiviral based on a substance from the shell of crustaceans

Several CSIC centres, including the Institute of Integrative Systems Biology (I2SysBio), located in the scientific-academic area of the Science Park of the University of Valencia, collaborate in the development of a compound effective against viral respiratory infections such as coronavirus SARS-CoV-2 and respiratory syncytial virus
A team from the Institute of Integrative Systems Biology (I2SysBio), a joint centre of CSIC and the University of Valencia, is collaborating in the development of a new antiviral compound based on chitosan, also called chitosan, a chitin-derived material, a natural substance present in the exoskeleton of crustaceans such as crabs and shrimps. In addition, other centres of the Higher Council for Scientific Research (CSIC), such as the Institute of General Organic Chemistry (IQOG), the National Agricultural and Food Research and Technology Institute (INIA) and the Valencia Institute of Biomedicine are also involved in the project (IBV), together with the Biomedical Research Center in Rare Diseases Network (CIBERER) and the Cooperative Research Center in Biomaterials (CIC biomaGUNE).

"The compound was designed in our laboratory on the basis of heparan sulfates, sulphated polysaccharides which are employed by a significant variety of viruses to adhere to the cell surface during the process of infection.", explains IQOG researcher Alfonso Fernández-Mayoralas. "Our polysaccharides act as a decoy by preventing the virus from attaching to epithelial cells, which prevents the infection process," adds Julia Revuelta, also an IQOG researcher.

Published in the journal Communications Biology, the study reveals that this drug blocks the entry of viruses into cells through a mechanism of irreversible action, and shows powerful activity against the virus that causes covid-1919, SARS-CoV-2, and respiratory syncytial virus (RSV), so it could be used as a treatment for viral respiratory infections by aerosols or inhalers even after infection.

The study reveals that this drug blocks the entry of viruses into cells through a mechanism of irreversible action, and shows powerful activity against the virus that causes covid-19, SARS-CoV-2, and respiratory syncytial virus (VRS), so it could be used as a treatment for viral respiratory infections by aerosols or inhalers even after infection

This work exemplifies how multidisciplinary approaches can lead to the development of new treatments. It is a collaborative effort led by chemists (IQOG), who designed and synthesized the compounds; virologists (I2SysBio and INIA), who selected the best candidates and characterized their antiviral activity; structural biologists (IBV), which helped to define the mechanism of action; and bioimaging experts (CIC biomaGUNE), who provided information on the behavior of the compound in vivo. 

Antiviral for common respiratory infections

Research has shown that this compound is able to inhibit infection by various variants of SARS-CoV-2, the virus causing covid-19, and by different strains of respiratory syncytial virus (RSV), which particularly affects infants and elderly people.

Experiments in cell cultures have shown that some of these compounds block viral entry by binding to proteins in the virus envelope, preventing them from attaching to cellular receptors. "The most promising compound was able to block infection by these viruses, both in cell culture models and in mouse infection models, even when administered after infection started," explains Ron Geller, an I2SysBio scientist.

"The compound works by binding directly to the virus and preventing it from entering cells. Since it was well tolerated in animals, these results suggest that it is an excellent candidate for further development as an antiviral treatment for these common viral respiratory infections", Ron Geller, I2SysBio scientist

In mice infected with SARS-CoV-2, administration of the antiviral before infection reduced viral load by more than six orders of magnitude. Even when applied after infection, a significant decrease in the virus was observed in the lungs of treated animals. "These results are very promising and give an idea of the antiviral potential of this type of compounds," says Miguel A. Martín Acebes, INIA scientist in charge of the antiviral efficacy trials of the compound in mice.

Similarly, in RSV infection models, the compound significantly reduced viral replication. "The compound works by binding directly to the virus and preventing it from entering cells. Since it was well tolerated in animals, these results suggest that it is an excellent candidate for further development as an antiviral treatment for these common viral respiratory infections," argues Ron Geller. Among its advantages, it highlights that "it works against multiple viruses, not only against a specific virus, and blocks the infection at an early stage, before the virus enters the cells, preventing the logarithmic proliferation of the virus".

Drug safe for repeated applications

"One of the most important findings from the study is that the compound not only prevents infection when administered before exposure to the virus, but is also effective as a post-treatment. This is particularly important in infections such as covid-19 and RSV, where early diagnosis could allow the application of therapies that reduce the viral load and severity of the disease," say IQOG-researchersCSIC Julia Revuelta and Alfonso Fernández-Mayoralas.

The researchers also tested the safety of the compound in animal models and found no signs of toxicity after repeated intranasal administration. In addition, through a selective chemical modification carried out at the IQOG it was subsequently possible to introduce a radioisotope in order to carry out biodistribution studies in Jordi Llop’s laboratory, at the CIC biomaGUNE. The results showed that the drug is eliminated from the body in approximately 48 hours, suggesting that its use could be safe for repeated applications.

Aerosols for future pandemics

Since the compound is based on chitosan, a polymer of natural origin abundant and widely used in the biomedical and food industry, its large-scale production would be viable and affordable. This opens the door to the development of formulations such as nasal sprays or inhalers for the prevention and treatment of viral respiratory infections. This breakthrough represents an innovative strategy to combat emerging and reemerging viral diseases, providing a valuable tool for rapid protection against future pandemics and for the control of seasonal respiratory infections, The researchers highlight.

Source: Delegation of CSIC Comunitat Valenciana