TMEM16 series
Develop optimized salicylamide derivatives with an improved drug property profile as broad-spectrum antivirals
current phase of drug development
updated 11 Mar 2025
DNDi is collaborating with the Translational Health Science and Technology Institute (THSTI) Faridabad, India, to identify affordable antiviral drugs effective against Influenza and other viruses of pandemic potential. The project focuses on the synthesis and optimization of novel salicylamide derivatives, which show potent antiviral activity against a range of different virus families, including orthomyxo, corona, and flaviviruses, with a low potential for the development of drug-induced resistance.
The current aim is to identify compound candidates with improved human plasma exposure compared to existing drugs – such as niclosamide and nitazoxanide – and to select a lead candidate compound suitable for pre-clinical studies. The project includes medicinal chemistry and pharmacokinetic studies, antiviral testing, and pharmacological evaluation.
Compounds included in the study will be analysed and assessed in two steps:
- Medicinal chemistry and pharmacokinetic studies of novel salicylamide derivatives
- Antiviral test cascade and pharmacological evaluation in vitro and in vivo of suitable lead compounds
All medicinal chemistry work is being performed in India with the goal of further strengthening academic drug discovery research in the country. The results of the project will be shared widely through open access publications.
Project updates
2024
New salicylamide derivatives with improved physiochemical profiles have been designed and synthesized, confirming that it is feasible to significantly improve the drug property profiles of compounds in the series. Work is now focused on improving the antiviral potency of the compounds in the sub-series and confirming a favourable plasma exposure profile before assessing in vivo antiviral efficacy.
2023
Salicylamides such as niclosamide and nitazoxanide exhibit potent antiviral activity for a broad range of different viruses, including SARS-CoV-2, dengue, and influenza viruses. The antiviral mechanism of action is not yet fully understood, although it is suggested that they act through host mechanisms by blocking key steps in viral uptake and excretion. Furthermore, it is reported that the antiviral activity is dependent on the interaction with the TMEM16F Ca2+ ion-channel/scramblase. Significant progress in 2023 included the identification of novel analogues showing improved microsomal clearance and the development of an improved understanding of antiviral structure relationships.
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