Back A molecule has been designed that shows antiviral efficacy against the AIDS virus, hepatitis C, West Nile and dengue fever
A molecule has been designed that shows antiviral efficacy against the AIDS virus, hepatitis C, West Nile and dengue fever
The study opens the way to developing a new family of panviral drugs capable of inhibiting several viruses at the same time and that would enable simplifying the treatment of people with more than one infection. There is currently no approved drug against the West Nile or dengue viruses.
Researchers at the Institute for AIDS Research IrsiCaixa and Pompeu Fabra University (UPF) have participated in designing a molecule that has proven to be effective against HIV and hepatitis C (HCV), dengue virus and West Nile virus. The compound was specifically designed to inhibit a cellular protein called DDX3, which is essential for the replication of viruses belonging to different families. Tests on cell cultures of the molecule have shown that it manages to inhibit the replication of the West Nile, hepatitis C and dengue viruses, as well as some strains of HIV resistant to antiretroviral drugs. This discovery opens the way for the creation of a new family of broad-spectrum antiviral drugs, acting against more than one virus at once. This would allow, for example, treating patients co-infected with HIV and HCV with a single drug. The study is published today in the journal Proceedings of the National Academy of Sciences (PNAS).
Viruses are infectious agents forced to act in a parasitic manner because they depend on the infected cell to reproduce. Based on this fact, a hypothesis currently being worked on is to try to block certain host cell processes necessary for the replication of several viruses. This approach would enable developing panviral drugs capable of inhibiting various viruses at once.
Thus, researchers from the University of Siena designed a family of molecules specifically to inhibit DDX3, a cell protein required for the replication of several viruses, including HIV-1 and HCV. “Noting that these molecules were particularly effective against HCV, we decided to test a prototype with viruses that had a genome or similar replication strategy to HCV, such as West Nile and dengue viruses. Our study shows that the use of a cell target may allow the design of panviral drugs”, explains Miguel Ángel Martínez, head of the IrsiCaixa HIV and HCV Genetic and Phenotypic Variability group. However, the effectiveness of the compound will require confirmation with further studies in vitro and in animal models before considering designing drugs based on it.
In addition, according to the head of the HIV Pathogenesis group at IrsiCaixa, Jose Esté, “being a different strategy to the ones currently known and addressing a cellular factor, rather than the virus, opens up the possibility of generating combinations of drugs that prevent the emergence of resistant viruses”. Martínez and Esté coordinated the evaluation of the antiviral activity of this new family of drugs. “We had observed broad-spectrum antiviral activity of compounds derived from microorganisms, but it is very interesting to observe the antiviral activity of molecules designed from scratch”, says Andreas Meyerhans, leader of the Virology Unit at UPF, which is responsible for conducting the antiviral tests against West Nile and dengue viruses.
Most antiviral drugs today focus on a single component or enzyme of a specific virus. Despite their therapeutic efficacy, these drugs can have deficiencies such as the development of resistance by the virus, low adherence (treatment follow-up) in some patients, or a certain degree of toxicity. The development of new molecules such as the ones in this study would enable simplifying the treatment of people co-infected by various viruses at the same time and acting against viral diseases against which there are no specific approved drugs. Among them, the dengue and West Nile viruses.
Moreover, toxicity studies have shown that DDX3 activity is essential for viral replication, but its inhibition is somewhat tolerated by the cell, so using it as a target would not damage the host cell to a large extent. Although it will be necessary to go into greater depth on the possible side effects of these molecules, DDX3 could serve as a target for a new family of broad-spectrum antiviral drugs that could include other viruses such as Ebola, Zika or Chikungunya.
HIV Currently, more than 36.9 million people in the world are HIV positive, with 2 million new infections in 2014. In Spain there are an estimated 150,000 people infected, 33,600 in Catalonia. In recent years the number of new cases has stabilized in Western Europe, due in part to decreased prevention, thanks to the existence of antiretroviral drugs that can control the disease but have a high cost and toxicity long term.
HCV Hepatitis C is a viral liver disease whose severity varies from a mild illness, lasting a few weeks (approximately 15-25% of infected people eliminate the virus spontaneously within six months, without the need for treatment) to a serious illness for life. It is transmitted through blood. Worldwide, between 130 and 150 million people are infected with HCV and approximately 500,000 die each year from liver disease, cirrhosis and hepatocellular carcinoma associated with this virus.
DEN Dengue is a viral infection transmitted by mosquitoes with similar symptoms to the flu and sometimes evolves to become potentially life-threatening, known as haemorrhagic dengue fever. It occurs in tropical and subtropical climates. According to a recent estimate, there are 390 million dengue infections each year, of which 96 million manifest clinically. Each year, approximately 500,000 people suffering from serious dengue -mainly children- require hospitalization. Approximately 2.5% of them die.
WNV The West Nile virus infection is spread primarily by the mosquito bite and is concentrated in Africa, Europe, the Middle East, North America and western Asia. It is asymptomatic in about 80% of infected people, and the remaining 20% can suffer West Nile fever, a serious condition characterized by fever, headache, fatigue, body ache, nausea, vomiting and, sometimes, a rash and swollen lymph nodes.