Dengue, also known as dengue fever, is caused by the Dengue virus (DENV) and transmitted via infected mosquitos. Worldwide, an estimated 96 million people suffer from dengue every year, with ± 10,000 fatal cases. These numbers are only expected to increase due to climate change, globalization, and the lack of control measures. As a result, an estimated 60% of the world's population will be exposed to this disease by 2080. This is a gloomy expectation, given that there are no good means to combat the disease yet!
Fortunately, there are promising drugs in the pipeline. But before a drug can be used in practice, a lot of research is necessary. For example, in the case of a drug, the safety, low susceptibility to resistance and efficacy must first be investigated in various animal models. Combining the strengths of different research groups is essential in this respect. For example, BPRC scientists were part of a large research collaboration that investigated the anti-dengue drug JNJ-1802.
Safety of JNJ-1802
Dengue can be caused by four different variants of DENV. It is therefore important to develop a cure that is effective against all variants. After much preliminary laboratory research, JNJ-1802, a compound with a good safety profile, has now been developed.
JNJ-1802 is effective against DENV in cell cultures and mice
First, the effectiveness of JNJ-1802 against DENV was tested in cell cultures by the researchers. The drug turned out to be highly effective against all four variants of DENV in cells grown in culture dishes. Subsequently, it was investigated in mice whether the drug could also counteract DENV in this species. It turned out that JNJ-1802 was not only safe, but also highly effective against the different variants of DENV in mice. An additional, but important advantage is that the virus does not appear to be able to quickly develop resistance against JNJ-1802.
JNJ-1802 tested in monkeys
Finally, the effectiveness of JNJ-1802 was also investigated in rhesus monkeys, because this animal species is closely related to humans and is also naturally susceptible to DENV. Efficacy against variant DENV1 was tested in the USA, while effectiveness against variant DENV2 was investigated at BPRC. In both studies, JNJ-1802 was highly effective against infection with the DENV variants and was also safe to use.
Can JNJ-1802 be applied in humans against DENV?
JNJ-1802 has already also shown to have a good safety profile in humans. So finally, we have now arrived at the burning question: is the drug effective in humans? This will be tested soon. The data from the monkey studies are very important for this, because they also assist in determining the best dosage. All in all, a remedy that can combat dengue is now more and more within reach. The results of the above work have been published in the leading journal Nature.