En antiviral mot flera högpatogena virala zoonoser
- Diarienummer
- FID15-0010
- Start- och slutdatum
- 161101-210701
- Beviljat belopp
- 2 500 000 kr
- Förvaltande organisation
- National Veterinary Institute
- Forskningsområde
- Livsvetenskaperna
Summary
Recent incidents of RNA viruses such as Ebola virus (EBOV) causing lethal hemorrhagic fever and an increasing number of Zika virus (ZIKV) cases have put pressure on finding new strategies to target emerging viruses, as to date no effective approved cure exists. Both EBOV and ZIKV and a number of other pathogenic viruses carry their genetic material as RNA that is vulnerable for oxidation and degradation. Cellular oxidative status is known to influence the antiviral defense system of host cells,but it remains unknown how viral RNA genome cope with oxidative stress and whether cellular DNA repair pathways are involved in the maintenance of viral genomic stability and in viral transcription and replication. We hypothesize that the base excision repair pathway of host cell may be crucial for RNA viruses, as it repairs oxidized bases from DNA and RNA. The proposed project aims to elucidate the interplay between the cellular DNA damage response and the life cycle of RNA viruses, focusing on understanding the role of DNA glycosylase OGG1 on transcription and replication of hemorrhagic fever viruses. The mode of action of newly synthesized OGG1 inhibitors that show antiviral properties will be studied first in hemorrhagic fever infections and later on in the context of other pathogenic RNA viruses such as ZIKV and influenza. Having an access to high containment laboratories together with state-of-the-art molecular biology resources will present unique settings to study this subject.
Populärvetenskaplig beskrivning
Outbreaks of emerging infectious diseases continue to challenge both human and veterinary health in Europe and around the world. The reported incidence of zoonotic vector-borne disease is increasing in many parts of the continent in Europe. The potential for bioterrorism through the deliberate release of an infectious agent in an area not previously affected adds a further dimension to the emergence of infectious disease and its control. At present, there is no effective cure against the most deadly viruses available and new approaches for targeting these highly pathogenic RNA viruses are needed. This is a narrow research field with a few top experts around the world and a limited number of capacity hubs. Altogether, it is clear that multidisciplinary research efforts need to be focused into a program on these diseases. We have succeeded to bring together selected competitive advantages; 1) operative capacity with appropriate facilities, 2) world-leading scientist within Biochemistry, 3) Expertise in the field of emerging viral diseases, 4) Interaction between Universities and governmental research institutes and 3) an international network through the PIs. This project will focus to develop a novel antiviral against these deadly viruses.