After WHO’s approval of the first malaria vaccine, another good news comes from the front dengue: a promising antiviral compound has been shown to be effective in blocking the mechanism of development of the virus, which affects 96 million people annually. It is still early to talk about a drug for human use, but the direction is the right one.
What is this infection
Dengue fever is caused by four viruses that are very similar to each other and is transmitted by mosquitoes which, in turn, have bitten an infected person: an indirect contagion, for which there is currently no specific cure or drug for prevention. Within 5-6 days of the sting, the disease may progress asymptomatically or manifest itself with very high fever accompanied by acute headaches, pains around and behind the eyes, severe pain in muscles and joints, nausea and vomiting, irritation of the skin that can appear on most of the body, with a mortality rate that can exceed 20%. And paracetamol is one of the few weapons we have so far to treat it.
Hope for the 110 countries in the world where the disease is still endemic today comes from the Katholieke Universiteit Leuven, in Belgium, where researchers have discovered a new mechanism of action of viruses and successfully tested an inhibitor on human cell cultures, with a safety profile currently only tested in mice and rats.
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The discovery, just published on Nature , comes from the team led by the virologist Johan Neyts who carried out a large-scale investigation to identify compounds that inhibit dengue viruses. The most promising – highly effective against all genetic variants of the four known serotypes, including 21 different viral strains isolated from infected individuals – was optimized in a compound, called JNJ-A07, tested in vivo. The experimentation thus demonstrated the net reduction of the viral load in mice, to which it was administered orally, both as a form of prevention and as a post-infection treatment.
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How the inhibitory system works
The mix of molecules is able to interfere with the replication of the virus, blocking viral proteins and revealing a completely new mechanism of action: “Although JNJ-A07 is not the first dengue inhibitor to be discovered, it is one of the most promising because , in addition to blocking replication in the blood, it makes the virus unable to replicate even in mosquitoes, thus creating a dead end, ”the researchers wrote. In short, a cure could be near.
In the only trial carried out to date, the research team infected immunosuppressed mice with highly lethal amounts of dengue and found that JNJ-A07 was effective as an antiviral: it rapidly decreased the levels of virus in the blood and reduced the production of cytokines, the signals inflammatory molecules that contribute to severe disease, just like in Covid, saving the life of guinea pigs. And it has been shown to be equally effective both when administered preventively and for therapeutic purposes, four to five days after infection.
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“We have shown that blocking the interaction between two viral proteins results in strong antiviral activity. And this interaction represents a promising target for the development of highly effective inhibitors ”.
There is also a vaccine: but it is only effective in some cases
There is a vaccine, Dengvaxia, developed by Sanofi Pasteur and approved in about 20 countries, but according to the WHO (https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe- dengue) “has proven effective only in those who have already had a previous infection with the virus, while it carries an increased risk of severe dengue in those who have their first natural infection after vaccination”, leading him to recommend it “are in patients with previous dengue, following an antibody test, as an integrated prevention strategy “.
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“Despite the immense effort made, no treatment is currently available against this RNA infection which evolves very quickly and represents a huge burden on public health, with about 3.9 billion people at risk”, recall the infectious disease specialists. Scott B. Biering ed Eva Harris of the University of Berkeley, California, in the accompanying editorial on Nature.
The two experts defined the Belgian discovery as “intriguing”, as well as promising: “The effectiveness of this compound obtained so far justifies the continuation of the experimentation of JNJ-A07 in non-human primates and then on humans”, representing in any case ” an important advance in the field of dengue therapy “. The times are not certain, as well as the results: research must go on, but it is certainly a step forward that will change the prospects for treatment.
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