Novel therapeutic agent for Tamiflu-resistant pH1N1 influenza virus discovered
Researchers at the Institute for Molecular Medicine Finland FIMM with their collaborators have shown that first Tamiflu resistant pandemic influenza pH1N1 viruses have emerged in Finland. Furthermore, they have identified a novel antiviral agent MK2206 and shown that the pH1N1 viruses are not able to develop resistance against it.
In 2009 the influenza pH1N1 virus caused the first flu pandemic in the 21st century. The virus reached Finland in May 2009 and killed more than 50 people in the country. Since 2011 the pH1N1 virus infects Finns mainly during flu epidemics (winter/spring seasons). Infections with influenza pH1N1 virus vary from asymptomatic to serious complicated illnesses. World Health Organization has recommended Tamiflu for treatment of patients with severe or progressive illness. The disadvantage of this drug is that it targets viral proteins which mutate quickly and the virus develops resistance to it.
The Medical Systems Virology group at FIMM, together with collaborators has recently sequenced genomes of 135 pH1N1 influenza strains isolated from Finnish patients in 2009-2013 and found one Tamiflu-resistant strain from the 2012-2013 epidemic season. The study was published in the Genome Announcements journal and is now available online.
"This finding suggests that there could be more resistant strains in upcoming seasons. Therefore, there is a need for the development of new antiviral agents against pH1N1", says Dr. Triin Lakspere.
In another study published this week the group investigated influenza pH1N1 virus-host cell interaction in detail and found that certain host function could be temporally inhibited with small molecule MK2206 to block influenza infection in cell culture.
"Importantly, the virus was unable to acquire resistance to host-directed MK2206 in contrast to virus-directed Tamiflu. This small molecule is in clinical trials against cancer and has high specificity and good pharmacological properties, which could warrant its further development as antiviral drug for treatment of pH1N1 virus infection", Dr. Oxana Denisova says.
For further information, please contact:
Dr. Denis Kainov
Institute for Molecular Medicine Finland FIMM
+358 50 415 235460
Lakspere T, Tynell J, Kaloinen M, Vanlede M, Parsons A, Ikonen N, Kallio-Kokko H, Kantele H, Mattila P, Almusa H, Julkunen I, Kainov D, Kakkola L. Full-genome sequences of influenza A(H1N1)pdm09 viruses isolated from Finnish patients during 2009-2013. Genome Announc. 2014. 2. pii: e01004-13.
Denisova OV, Soderholm S, Virtanen S, Von Schantz C, Bychkov D, Desloovere J, Theisen LL, Tynell J, Ikonen N, Vashchinkina E, Nyman TA, Matikainen S, Kallioniemi O, Julkunen I, Muller CP, Saelens X, Verkhusha VV, Kainov DE. Akt inhibitor MK2206 blocks pH1N1 influenza virus infection in vitro. Antimicrob Agents Chemother. Online early publication.