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New strategy in creating broad-spectrum antiviral drugs
In its latest edition, the Journal of Hepatology has published the results obtained by the Molecular Virology Research Group at the Department of Experimental and Health Sciences (DCEXS) at UPF, directed by Juana Díez, focusing on obtaining an antiviral drug that can be used to treat various infections. The study has also involved the collaboration of Andreas Meyerhans, head of the Infection Biology Laboratory, also of the DCEXS, and Mark Brönstrup, head of the Chemical Medicine Department at the Helmholtz Center for Infection Research in Germany.
The idea that a single drug can treat different microbes is common in bacteriology. Not having necessarily to identify which specific bacterium has caused an infection allows for a very quick response: a broad-spectrum antibiotic is prescribed.
With viral infections this is not possible. There are currently very few antiviral drugs and those that exist are specific to one type of virus, requiring a diagnostic process before being able to apply treatment. The development of broad-spectrum antivirals would speed up the prescription of treatments, which in many cases, is essential to beat the disease, and would provide a first line of defence against new viruses. "Antiviral drugs on the market today are aimed at specific components of a virus, usually viral enzymes necessary for the multiplication of the virus in infected cells", explains Georgios Koutsoudakis, researcher of Juana Díez's group and first author of the study. Bearing in mind that viruses of different families are genetically quite different, direct action antivirals are tailored to a specific type of virus.
The team of Juana Díez has warned that different viruses may need the same components of the host cell to complete their life cycles. In collaboration with the teams of Andreas Meyerhans and of Mark Brönstrup, it has shown that a natural component can inhibit two very different viruses, human immunodeficiency (HIV) and hepatitis C (HCV). Moreover, its potential as an inhibitor of HCV is just as good as an anti-HCV drug already present on the market. This compound is SoraphenA, a product extracted from soil myxobacteria that is targeted at the cellular enzyme Acetyl-Coenzyme A Carboxylase (ACC), a protein involved in the synthesis of lipids within cells. The great advantage of this compound is that because its antiviral activity is mediated by a cell component, it is effective for various genotypes of HCV and is little susceptible to developing drug resistance.
Given that not only HIV and HCV but many other viruses, including the emerging Dengue virus, West Nile virus and Chikungunya virus, depend on the lipid cellular metabolism to multiply, it is possible that the antiviral activity of SorA will go beyond HIV and HCV, which is something that the laboratories of Dr. Díez and Dr. Meyerhans are already testing.
The concept of broad-spectrum antivirals targeting host cells and obtained from nature as well as the characteristics of the inhibition of HCV mediated by SorA are published in two articles. It is still very early to speak of SorA in treatment. From an antiviral compound being effective in cell cultures to it coming to be used on patients is very long process. But the experimental discoveries so far are very promising.
Articles of reference:
Koutsoudakis G, Romero-Brey I, Berger C, Pérez-Vilaró G, Monteiro Perin P, Vondran F, Kalesse M, Harmrolfs K, Müller R, Martinez J, Pietschmann T, Bartenschlager R, Brönstrup M, Meyerhans A, Díez J. Soraphen A: a broad-spectrum antiviral natural product with potent anti-hepatitis C virus activity . J. Hepatol (2015) (Epub ahead of print).
J. P. Martinez, F. Sasse, M. Brönstrup, J. Diez and A. Meyerhans. Antiviral drug discovery: broad-spectrum drugs from nature . Nat. Prod. Rep., 32 (1), 29-48 (2015).