Abstract
Global spread and the ability to infect a wide host range including humans underline the importance of influenza A viruses (IAVs) as an omnipresent threat with pandemic potential, which has already been demonstrated by large and devastating outbreaks in the last decades. Animal derived IAVs like avian influenza viruses (AIVs) can cause severe disease in humans which require therapeutic interventions. Since human vaccines only cover a limited range of circulating IAV strains and many strains have been shown resistance to available antiviral drugs, new approaches are necessary to counteract this pathogen in the future. Thus, we are exploiting antiviral drug combinations that target both host and viral factors. To achieve synergistic effects in the inhibition of virus replication, we have combined nucleoside analogues with pyrimidine synthesis inhibitors tha target enzymes essential for intracellular CTP production. AIVs of H5 subtypes as well as different swine influenza A viruses with zoonotic potential were tested in vitro for their sensitivity against different drug combinations. All strains tested to date were sensitive to drug treatments, albeit with varying levels of effectiveness. To further validate this drug efficacy in vivo, initial animal trials in ferrets infected with AIV H5N1 have been performed. In conclusion, this approach may lead to new therapeutic strategies against significant zoonotic pathogens with a decreased risk of antiviral resistance.
Co-Author(s)
David Scheibner1, Leon Schrell2, Annika Graaf-Rau3,4, Kim Klein2, Antje Dickmanns2, Hannah Fuchs2, Sandra Diederich1, Matthias Dobbelstein2 and Anne Balkema-Buschmann1
1Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Germany
2University Medical Center Göttingen, Germany
3Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Germany
4 Department of Pathogen Evolution, Helmholtz Institute for One Health, Germany
Abstract Category
Avian influenza in mammals, pandemic preparedness, and one health