Development of an effective inhibitor against influenza A viruses

The Heinrich Pette Institute, Leibniz Institute for Experimental Virology (HPI), the Universität Hamburg (UHH) and the Hamburg-based company Evotec SE are funded for a joint project to further develop an inhibitor against influenza A viruses.

Emerging influenza A viruses pose a serious risk of causing large epidemics or even pandemics. An important hallmark of pandemic preparedness is the development of effective and broad-acting antiviral therapeutics. However, currently available antivirals for the treatment of influenza virus infections do not provide broad protection against different subtypes of influenza A virus.

One inhibitor already known is the active ingredient T-705 (favipiravir, Avigan®), which shows activity against various influenza A and influenza B viruses as well as against other RNA viruses. However, its clinical use is severely limited due to its low efficacy and teratogenic and embryotoxic potential.

The joint project "NoVIR-Flu" of HPI research department head Prof. Gülsah Gabriel and Prof. Chris Meier from the Institute of Organic Chemistry at the Universität Hamburg and the company Evotec aims at modifying the chemical structure of the active form of T-705 (T-705-RTP) to provide an optimized and potentially broadly effective inhibitor against influenza A and other RNA viruses. In particular, Evotec will provide its expertise and technology platforms in the areas of 'compound profiling' and 'ADME' for this project.

"T-705 is a nucleobase analog that, in the form of its active metabolite T-705-RTP, inhibits influenza virus polymerase. New, non-teratogenic and influenza A virus subtype-spanning T-705 derivatives will be developed in this research project," explains Prof. Gülsah Gabriel. 

"T-705-RTP derivatives are designed to penetrate the infected cells, release the actual drug directly and block the influenza-specific polymerase," adds Prof. Chris Meier.

The project is supported by the Hamburg-based cooperation platform "BRIDGE 53" (call for proposals 2019). The aim of the cooperation platform is to find and characterize new anti-infectives and to transfer the scientific findings generated into application as quickly as possible. The "NoVIR-Flu" project aims to contribute to the effort to combat the annually recurring influenza infections. The funding is provided by the Free and Hanseatic City of Hamburg (Ministry of Science, Research, Equalities and Districts, BWFGB).

Project: NoVIR-Flu: Design and evaluation of T-705 -derived, new inhibitors of viral RNA-dependent RNA polymerase against a broad range of influenza A viruses