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Identification of chemical compounds that halt virus replication

Identification of chemical compounds that halt virus replication

Also this week MedZine brings you the latest medical news on various medical specialisms. In this editorial we report about an exciting development in the field of anti-viral treatment.

Researchers at Boston University School of Medicine have identified a new class of compounds that inhibits the replication of nonsegmented, negative-strand RNA viruses. This group of viruses includes the causative agents for mumps, measles and rabies as well as deadly viruses, such as Ebola. This finding opens up the way to the development of broad-spectrum antivirals.

There are many broad-spectrum antibiotics used to treat a wide range of bacteria. For viruses there is currently no effective and safe broad-spectrum drug available. The ability of viruses to rapidly mutate within a host often results in a loss of effectiveness of drugs targeting a specific virus. The development of a broad-spectrum antiviral would decrease the risk that a virus can evade it upon mutation, since these drugs will probably target processes that are essential for the virus. In addition, a broad-spectrum antiviral could also be used against new, emerging viruses.

Viruses are classified based on the type of nucleic acid used to carry their genes, i.e. DNA or RNA. They are further classified based on the number and directionality of the nucleic acid strand. Negative-strand RNA viruses have a single strand of RNA that first needs to be copied to positive-strand RNA, which is then translated to proteins.

“The development of broad-spectrum antivirals is a great way to provide treatment in the future. Towards this end, we have identified a drug that targets multiple viruses- and may be developed into an antiviral treatment for known and emerging viruses” says Claire Marie Filone, first author on the study published in Chemistry & Biology.

The researchers used a screen to identify small molecules that show strong antiviral activity but little cell toxicity. They found that a set of indoline alkaloid-like compounds inhibit replication in a number of viruses, including Ebola. One of these compounds was investigated further and it is most likely that this compound inhibits the viral RNA-dependent RNA polymerase; a polymerase used by all nonsegmented, negative-strand RNA viruses.

“Because the production of viral RNA is the first step in successful replication, it appears that we have uncovered an Achilles heel to halt virus replication,’ said Filone. “These compounds represent probes of a central virus function and a potential drug target for the development of effective broad-spectrum antivirals for a range of human pathogens.”

Source: Eurekalert and Chemistry & Biology


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