Drug repurposing approaches to discover arbovirus inhibitors

Tuesday 19 September 2023, 10:30 am
PhD student
F. Meutiawati
prof. dr. ir. R.P. van Rij
dr. F.S. Varghese (UniQure)

Arthropod-borne (arbo)-viruses are a group of viruses that are transmitted primarily by mosquitoes and a common cause of disabling fever syndromes worldwide. Dengue virus (DENV) and Chikungunya virus (CHIKV) are the mosquito-borne arboviruses with the most significant global burden. Along with vaccines and vector control, antiviral drugs could be an important tool to fight the burden of arbovirus infections. In this study, a drug repurposing method was used to identify compounds with antiviral activity in a library of small drug-like molecules with known biological activities that are used for other therapeutic purposes. We identified posaconazole (PCZ), an established antifungal drug, as a potential antiviral against DENV and CHIKV by targeting oxysterol binding protein and early stage of CHIKV virus life cycle, respectively. We also explored the potential of small molecules known to inhibit DENV replication in mammalian cells as an approach to block virus transmission in mosquitoes. Our results provide proof-of-principle that small molecule antivirals can be used to inhibit DENV replication in Ae. aegypti, which may serve as a basis to develop intervention strategies to inhibit arbovirus transmission.

Febrina Meutiawati obtained her Master’s Degree from the Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung (ITB), after which she worked as a Research Assistant in Eijkman Institute for Molecular Biology.  In April 2016, she received a scholarship from the Indonesian Endowment Fund for Education (LPDP) to pursue her PhD at the Department of Medical Microbiology at the Radboudumc, under the supervision of Prof. Ronald van Rij. Currently, she is working in Exeins Health Initiatives (EHI) as a Scientific Advisor.