BUSCADOR RECOLECTA

13 Pág., Flaviviruses affect the lives of millions of people in endemic regions and also have the potential to impact non-endemic areas. Factors such as climate change, global warming, deforestation, and increased travel and trade are linked to the spread of flaviviruses into new habitats and host species. Given the absence of specific treatments and the limited availability of vaccines, it is imperative to understand the biology of flaviviruses and develop rapid and sensitive diagnostic tests. These measures are essential for preventing the transmission of these potentially life-threatening pathogens. Flavivirus infections are mainly diagnosed using conventional methods. However, these techniques present several drawbacks, including high expenses, time-consuming procedures, and the need for skilled professionals. The search for fast, easy-to-use, and affordable alternative techniques as a feasible solution for developing countries is leading to the search for new methods in the diagnosis of flaviviruses, such as biosensors. This review provides a comprehensive overview of different biosensor detection strategies for flaviviruses and describes recent advances in diagnostic technologies. Finally, we explore their future prospects and potential applications in pathogen detection. This review serves as a valuable resource to understand advances in ongoing research into new biosensor-based diagnostic methods for flaviviruses., This work was supported by the Spanish Ministry of Science and Innovation AEI under grant PID2020-119195RJ-I00 (to NJO)., Peer reviewed

West Nile virus (WNV) is a neurotropic flavivirus transmitted by the bites of infected mosquitoes. Severe forms of the disease include meningitis, encephalitis, acute flaccid paralysis, or even death, and survivors develop long-lasting sequelae. The damage induced by WNV does not only stem from viral multiplication but also arises from immune-related pathology linked to neuroinflammation. Certain sphingolipids are key players in WNV infection, neurodegenerative diseases and inflammatory disorders. Neutral sphingomyelinase 2 (nSMase2), catalyzes the conversion of sphingomyelin into ceramide and is essential for flavivirus multiplication. Thus, nSMase2 constitutes a promising therapeutic target for the development of dual-acting antiviral and anti-inflammatory therapies against WNV. The effect of an orally bioavailable and brain-penetrating prodrug of the potent nSMase2 inhibitor DPTIP (DPTIP-P1) was studied in WNV-infected mice. While no reduction in the viral load in the brain of infected animals was observed, WNV-induced expression of inflammatory markers was modulated, resulting in a reduced IL-1β expression in brain. Transcriptomic analyses revealed that treatment with the DPTIP prodrug also modulated the expression of various genes related to immune cell function without altering antiviral innate response. Among others, DPTIP-P1 reduced the expression of Lyz2, an inducible genetic marker associated with macrophage infiltration, and modified the expression of genes related to T cell activation such as Trbc1 and Ptnp22. These results identify nSMase2 inhibitors as a new type of immune modulators of WNV infection. The neuroprotective effects exerted by DPTIP-P1 could contribute to mitigate WNV-induced neuroinflammation and sequelae., This work was supported by the Spanish Ministry of Science and Innovation AEI/10.13039/501100011033 under Grants PID2019- 105117RR-C21 (to MAMA), PID2019-105117RR-C22 (to MJPP) and PID2020-119195RJ-I00 (to NJO); Spanish Ministry of Science and Innovation AEI/10.13039/501100011033 and FEDER, EU under grants PID2022-137372OR-C21 (to MAMA), PID2022-137372OR-C22 (MJPP and EMP), by Comunidad de Madrid under grant TEC-2024/BIO-66/ SALAINDEC-CM (to MAMA) and by the European Commission—NextGenerationEU through CSIC’s Global Health Platform (PTI Salud Global). PMC was supported by an FPI fellowship from AEI/ 10.13039/501100011033 under Grant PRE2020-093374. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication., Peer reviewed