Choose Your Weapon in the War on Viruses

From the flu to Ebola, a large number of epidemics are caused by viruses. If antiviral treatments exist, their effectiveness remains limited and they can only rarely completely stop the spread of an infection. Researchers from the University of Geneva (UNIGE), EPFL and the University of Manchester are now on the verge of considerably strengthening the therapeutic arsenal against viruses: by modifying sugar molecules, they have succeeded to destroy, by simple contact, many viruses, and in particular those responsible for respiratory infections and herpes infections. These results, to be discovered in the journal Science Advances, could quickly lead to the development of broad-spectrum antiviral drugs capable of destroying many viruses, including probably the coronavirus which is currently rampant in China.

So-called "virucidal" substances, such as bleach, are capable of destroying viruses by simple contact. However, they are extremely toxic to humans and the environment and cannot be absorbed or applied to the human body without causing serious damage. From a medical point of view, most of today's antiviral drugs work by inhibiting the growth of viruses, but failing to destroy them. In addition, they are not always reliable: viruses can indeed mutate and become resistant to these treatments. "To get around these two obstacles and be able to effectively fight against viral infections, we imagined an entirely different angle of attack," underlines Caroline Tapparel Vu,

A simple contact is enough

The researchers had previously produced a gold-based antiviral.Using the same concept, this time they succeeded in developing an antiviral using natural glucose derivatives, called cyclodextrins. "The advantages of cyclodextrins are numerous: even more biocompatible than gold, and easier to use, they do not trigger a resistance mechanism and are not toxic," said Samuel Jones, researcher at the University of Manchester and member of the Henry Royce Institute for Advanced Materials. "In addition, cyclodextrins are already widely used, particularly in the food industry, which would facilitate the marketing of pharmaceutical treatments using them," adds Valeria Cagno, researcher at the Faculty of Medicine at UNIGE and co- first author of this work.

How does it work? The modified sugar molecules attract viruses before irreversibly inactivating them. By disrupting the outer envelope of a virus, they manage to destroy infectious particles by simple contact, instead of only blocking viral growth. And this mechanism seems to be verified regardless of the virus concerned. A patent has also been filed and a spin-off created to study the pharmaceutical development that could be made with this discovery. Very stable, cyclodextrins could thus be formulated as a cream, gel or nasal spray, for example.

Hope against epidemics

If there are drugs against certain viruses, such as HIV or hepatitis C, these remain specific. The development of new antivirals is therefore essential, especially to fight against the most devastating viruses or emerging viruses against which there is currently no treatment. Thus, broad spectrum antivirals would allow viral outbreaks to be controlled more quickly and more effectively. “If we succeed in this transition to concrete applications, our work could have a global impact. Our compound could also be effective against new emerging viruses such as the recent coronavirus which is currently causing concern in China ”, conclude the authors.

Reference
Samuel T. Jones, et al. Modified Cyclodextrins as Broad-spectrum Antivirals. Sciences Advances (2020). DOI: 10.1126 / sciadv.aax9318.

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