They discover a new antiviral against herpes simplex

An international team of researchers, led from the Severo Ochoa Molecular Biology Center (CBM-CSIC-UAM)a joint center of the CSIC, an organization attached to the Ministry of Science, Innovation and Universities, and the Autonomous University of Madrid (UAM), has identified a new compound with great potential as an antiviral drug against the herpes simplex virus.

Inspired by a drug already used against influenza, the new candidate, called LN-7, blocks the process by which this virus packages its genetic material, an essential step to form new viral particles and spread in the body. The new compound manages to act even against strains that have developed resistance to current treatments, which only control outbreaks without eliminating the virus.

The discovery, published in the magazine Advanced Sciencerepresents a significant advance in the search for alternative treatments for this persistent infection and, in many cases, resistant to available medications.

The new candidate, called LN-7, belongs to a family of molecules inspired by the structure of baloxavir marboxil, an anti-flu drug approved in several countries. Unlike classic antivirals such as acyclovir – which act on the viral DNA polymerase –, LN-7 blocks a distinct and critical processspecifically the nuclease activity that participates in the packaging of the viral genome within infectious particles.

This mechanism makes LN-7 a “first-in-class” antiviral, as efficacy against this therapeutic target has never before been demonstrated in the context of herpesvirus infections. According to the authors, This type of strategy not only expands treatment options, but can also help combat the growing problem. of resistance to conventional antiviral drugs.

According to the researchers “The results are promising”since LN-7 demonstrated antiviral activity in infected cells and also in animal models (mice) with HSV-1 infection. In addition, it showed efficacy against acyclovir-resistant strains, which underlines its potential as a second-line treatment or in combination with other antivirals.

“Our results show that LN-7 is not only effective against herpes simplex virus infections, but does so through a completely new mechanism”says CBM researcher and study coordinator, Dr. Luis Menéndez-Arias.

“By blocking the packaging of the viral genome, we open the door to a new class of antivirals that could complement or replace current treatments in cases of resistance or toxicity. “This represents an important conceptual advance in the fight against herpesviruses.”he states.

The next step will be delve into toxicity, bioavailability and efficacy studies in more complex models before considering clinical trials in humans. Even so, they state “the discovery marks a milestone in the research of new antivirals and opens the possibility of designing therapies aimed at the packaging of the viral genome, a hitherto unexplored target.”

Limitations of treatments

Herpes simplex virus, both type 1 (HSV-1) and type 2 (HSV-2), causes chronic infections that affect millions of people around the world. Although drugs such as acyclovir, valacyclovir or famciclovir are widely used and effective in controlling symptoms and their ability to reduce outbreaks, they do not eliminate the virus from the body. Furthermore, prolonged use, especially in immunocompromised patients, may favor the emergence of resistant strains.

In cases where first-line antivirals do not work, second-line options such as cidofovir or foscarnet are used. However, These drugs have serious side effects that limit its application. Hence the urgency of exploring new molecules with different mechanisms of action and more favorable safety profiles.

A future drug candidate LN-7 represents a unique opportunity to diversify the therapeutic arsenal against herpes simplex. Its effectiveness in preclinical studies suggests that it could be useful both in monotherapy and in combination treatments with other antivirals, which would increase the probability of clinical success and reduce the risk of the emergence of resistance.

The work has been directed by doctor Menendez-Arias and has had the participation of the doctor’s groups José Antonio López-Guerrero (CBM-CSIC-UAM), from doctor Federico Gago (University of Alcalá) and researchers from Shandong University in Jinan (China). This international collaboration has allowed us to unite knowledge in molecular biology, structural virology and drug design.