INVESTIGATING THE POTENTIAL OF ANTIVIRAL DRUGS AS TRANSMISSION-BLOCKING AGENTS IN MOSQUITOES

• Grant number: 25/19547-7
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: February 27, 2026
• End date: February 26, 2027
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Rafael Elias Marques Pereira Silva
• Grantee: Luiza Leme
• Supervisor: Leen Delang
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Campinas , SP, Brazil
• Institution abroad: University of Leuven, Leuven (KU Leuven), Belgium
• Associated to the scholarship: 23/10771-6 - Functional study of Envelope Protein N-Glycosylation on St. Louis encephalitis virus Infection., BP.DR

Abstract

Arthropod-borne viruses (arboviruses), such as St. Louis Encephalitis virus (SLEV), Dengue virus (DENV), Chikungunya virus (CHIKV), and Zika virus (ZIKV), pose a significant global threat, as they cause millions of infections annually, resulting in substantial public health and socioeconomic burden. Despite the high morbidity associated with these infections, there are currently no approved antiviral therapies and vaccines are available against a few arboviruses only. Given the impracticality of developing virus-specific treatments for over a hundred known arboviruses, a promising alternative is the development of broad-spectrum antivirals to disrupt viral transmission at the vector level. While antiviral drug development has typically focused on treating infected humans, an innovative and underexplored strategy is to target virus replication within the mosquito vector itself, blocking transmission at its source. This concept has been explored in the context of malaria, however, only a limited number of studies have investigated the potential of antiviral compounds to suppress arboviral replication in infected mosquitoes. Building upon the expertise of the research group of Dr. Leen Delang at KU Leuven, we aim to investigate the mechanism of action of Compound series 6, a new class of small molecules with potent, broad-spectrum activity against alphaviruses. Although effective in vitro, its mechanism remains unknown. We hypothesize that the Compound series 6 inhibits alphavirus replication by a defined mechanism and that it could be used as an arbovirus transmission-blocking antiviral compound. To test this, we will identify resistance-associated mutations in CHIKV by genotyping drug resistant CHIKV variants in cell culture and reverse-engineering identified mutations into reporter viruses to assess the involvement in the resistant phenotype. We will also assess its efficacy in mosquito vectors through a combination of in vivo infection models, ex vivo mosquito gut assays, and testing the drug in mosquitoes. The Delang Laboratory at KU Leuven provides an ideal environment for conducting this research due to its recognized excellence in mosquito virology and vector-pathogen interaction studies and being uniquely equipped to support the proposed investigations, particularly those involving mosquito models. This project adds to the ongoing collaboration between CNPEM and KU Leuven and represents a unique opportunity for the professional development of the proponent as a scientist in the field of arbovirology.