DNDi and our partners are working to accelerate research to prepare for future viral pandemics. Utilizing our experience in non-profit drug development and partnerships with medical research institutions worldwide, our drug discovery teams are focused on identifying new broad-spectrum antivirals targeting several families of viruses recognized by WHO as presenting the greatest epidemic and pandemic potential in humans. Employing open science, AI, and cutting-edge research tools, our goal is to advance new drug candidates through Phase I safety trials to have them ready for testing against emerging viruses with pandemic potential.
Our progress in 2025 includes:
Drug discovery
Nucleoside Booster: The results of the final batch of compounds have been generated. In total, 125 nucleosides have now been assayed in duplicates in a single concentration of 10 µM in 24 different viral assay systems using two different cell lines per virus (Chikungunya, dengue, Zika, Ebola, Marburg, Nipah, Lassa, MERS, SARS-CoV2, influenza, and Crimean-Congo viruses). The 25 nucleosides that displayed the most promising activity in these assays have been resupplied and measured in dose-response in the same assay systems covering the 10 viral diseases. The 6 compounds that displayed a broader spectrum of activities have been further evaluated in 14 different viral assays systems covering the same 10 virus types in primary human cell lines or monocytes. The results generated as part of this project will be made broadly available to the scientific community by our DZIF partners through publication in the Reframe database hosted by the Scripps Research Institute.
TMEM16 series: The lead optimization programme yielded compounds with significantly improved physiochemical profiles, as well as in vivo exposure approximately 100 times higher than the original lead compound, niclosamide. The optimized compounds are now being evaluated in both in vivo and in vitro infection models, and are showing potent in vitro efficacy across several viral families, including dengue, chikungunya, zika, SARS-CoV-2, and oropouche viruses.
AViDD ASAP: The ASAP lead optimization project focused on progressing the discovery of broad-spectrum flavivirus inhibitors. Recent developments in the NS2B_NS3 protease project confirmed that the compounds showed antiviral activity for both dengue virus serotype 2 and Zika virus. These compounds are now being further optimized to allow for in vivo proof-of-concept studies.
Flavivirus screening: High-throughput screening of all 20,000 compounds against both dengue and Zika viruses at a concentration of 10 µM were completed by IPK and all active compounds with dose-response assays were validated. A counter screen of the active hits using Eisai’s molecular beacon-based fluorescent helicase assay identified three distinct chemical series that inhibit NS3 helicase and suppress viral growth in both dengue and Zika cellular assays. These three series are undergoing further enrichment through additional analogue testing at IPK and Eisai and are being considered for advancement to the hit-to-lead phase.
Translational research
ASAP-0017445: ASAP-0017445 progressed through the first phase of toxicology studies and is progressing towards the next stages, including GMP synthesis of the active pharmaceutical ingredient, formulation development, and GLP toxicology studies. The structure of ASAP-0017445 was publicly disclosed in March 2025. The compound was nominated as a pre-clinical candidate in September 2025.
Photo credit: Stuart March-DNDi
