Thanks to a collaboration with the University of Siena and CNR of Pavia, a novel strategy to fight West Nile Virus and other emergent viruses
Following their recent study that led to the identification of the first molecule able to inhibit the replication of several viruses (such as Hepatitis C, HIV, Dengue) through the action on a cellular enzyme (DDX3), the research groups coordinated by Prof. Maurizio Botta from the University of Siena and Dr. Giovanni Maga from the IGM-CNR Pavia, also in collaboration with Lead Discovery Siena and Prof. Giannecchini from the University of Florence, have developed a novel family of DDX3 inhibitors which have been shown to be efficacious to block the replication of West Nile virus in human cells, without any damage to healthy cells.
These molecules, with promising pharmacokinetic properties, pave the way for the formulation of an innovative class of drugs directed against West Nile virus and other emergent viruses. The research has been published on the prestigious Journal of Medicinal Chemistry, published by the American Chemical Society.
West Nile virus is most commonly spread to people by the bite of infected mosquitoes that are also present in Italy where it is responsible for several infections each year, even with severe neurological complications. Moreover, this virus infects each year millions of persons all over the world. Despite continuous efforts being made to identify new drugs or vaccines, no specific therapy or prophylaxis is actually available on the market.
“Our approach – commented Prof. Botta and Dr. Maga – is highly innovative because exploits a cellular enzyme to block virus replication. Actually, it makes the cell an adverse environment for virus replication. Usually, antiviral drugs are directed against viral proteins which rapidly mutates and thus might become resistant to treatments. On the other side, our strategy is able to overcome this obstacle. Other viruses, such as Dengue and Zika, depend on DDX3 for their replication. Thus, our molecules could become broad spectrum antiviral therapeutic agents – not available so far – against emergent viruses. The good scientific research conducted in our Universities and at CNR has played a leading role in achieving such success. This work was made possible thanks to the precious economic support from Tuscany Region through the FAS Salute 2014 Grant (DD 4042/2014) and from First Health Pharmaceuticals B. V.”.
Published article on Journal Medicinal Chemistry
Maurizio Botta, LDS CEO, gives an interview on a popular television programme in Italy, dedicated to health and welfare.
Maurizio talks about the project on DDX3 inhibitors as antiviral agents active against HIV and Hepatitis C, among the others.
Maurizio’s research group together with the Molecular Genetics Institute of CNR in Pavia, identified the first molecules targeting DDX3, a human protein involved in the replication of many viral pathogens. During its interview, Maurizio outlines the innovative strategy which underpins the research project on DDX3 inhibitors, and recalls the history of this exciting discovery which mainly involved Italian research groups.
LDS is now taking part to the development of these broad spectrum antiviral agents thanks to its expertise and competences in discovery and development.
The show aired on 23th May 2016.
Maurizio Botta, and researchers from University of Siena and LDS, were really honoured they had the chance to tell their story about DDX3 to the Italian Nobel Prize winner Dario Fo.
The Italian recipient of the 1997 Nobel Prize in Literature, Dario Fo, and his wife Franca Rame, privately contributed to support the DDX3-inhibitor project through the Rame-Fo Foundation. Soon after the publication of the important results achieved in the project, and published in PNAS publication, Dario Fo expressed his enthusiasm about it in his web page:
Unfortunately, Franca Rame passed away before learning the results of her efforts but the researchers working on DDX3 are all incredibly grateful for her support and for believing in this pioneering project.
On 6th May, Dario Fo invited the researchers working in the DDX3 Project for a meeting at the “Libera Università di Alcatraz” founded by his son Jacopo Fo and they spent a wonderful day they’ll never forget with him. Here is a video about the interview.
All the DDX3 researchers would like to express a huge thank you to Dario Fo and to his group for all the effort and the great support to this work, which LDS is also actively contributing to. This is a really precious endorsement for all of them.
LDS is project partner in UNAVIR Project (Malattie Virali Rare: una strategia innovative per combatterle con un unico agente antivirale), together with University of Siena (lead institution), University of Florence, University of Pisa, and VisMederi.
UNAVIR is beneficiary of the “FAS Salute 2014” Call of Tuscany Region and is supported by Distretto Toscano Scienze della Vita.
The project aims at developing broad spectrum antiviral agents able to stop the progression of several viral diseases, such as Dengue and Chikungunya fever. By choosing a human protein as the biological target, it will be possible to overcome the resistance which is commonly developed by viral proteins against drugs. It is an innovative therapeutic approach for the treatment of rare viral infections including Dengue, Chikungunya fever, and West Nile viral disease, and whose incidence is constantly growing.
Within UNAVIR, LDS will guide the design and synthesis of new molecules which will be then tested in vitro by the other partners.