The Drugs for Neglected Diseases initiative (DNDi) and the Translational Health Science and Technology Institute (THSTI) of India are collaborating in the field of drug discovery to improve and optimize promising molecules that could become affordable, broad-spectrum antiviral treatments for influenza and other viruses of pandemic potential. The project is enabled through financial support from the Novo Nordisk Foundation’s strategic Pandemic Antiviral Discovery Partnership.
Initiated in March 2024, this lead optimization project focuses on the TMEM16 series of compounds, part of DNDi’s R&D programme for pandemic preparedness.
Respiratory viruses of pandemic potential such as influenza pose a major risk to human health. The development and availability of effective antivirals are essential in mitigating the impact of these viruses and protecting public health. However, there are only a limited number of antiviral drugs currently available, and few new antiviral drug candidates in later-stage development that could enter clinical trials to test their safety and efficacy when new pandemic threats emerge.
A class of molecules called salicylamides provide an attractive starting point for the development of novel, resistance-resilient treatments for influenza infections. Like other ‘host-directed’ therapies, salicylamides prevent viruses from entering human cells and using cell machinery to replicate. Although compounds in this chemical class have presented promising results in earlier clinical trials, their drug property profile prevents the achievement of optimal human plasma and tissue exposure.
The project led by DNDi and THSTI therefore aims to modify the structure of investigational compounds to improve the human exposure and obtain good candidates for pre-clinical studies. Given their broad-spectrum activity, salicylamides could target not only influenza A and B infections, but also other viruses such as SARS-CoV-2, Nipah virus, Chikungunya, and dengue.
Partners’ efforts have focused on the synthesis and profiling of novel, potent salicylamide derivatives and prodrugs with optimized physiochemical and pharmacokinetic properties to provide improved human plasma exposure compared to niclosamide and nitazoxanide while maintaining potent influenza activity. The project includes medicinal chemistry and pharmacokinetic studies, as well as pharmacological evaluation, including antiviral testing.
Scientific results from this project will be shared widely through open-access publications.
THSTI is a leading translational research institute funded by the Government of India with wide-ranging and renowned expertise in influenza virus pre-clinical models; DNDi is a non-profit drug development organization developing new, safe and accessible medicines for the most neglected populations. Their collaborative project aims to bridge gaps in research and development in India targeting new treatments that will be affordable and accessible for vulnerable communities.
Photo credit: Matt Bouch-DNDi
