New drug hope in the fight against viruses
avenues in drug development resulting in novel therapies for the
treatment of poxviruses such as variola virus, the cause of
smallpox.
The research is a welcome piece of news for pharmaceutical research as developing antivirals poses a unique set of problems. Antiviral drugs work by interfering with viral replication. Because viruses are tiny and replicate inside cells using the cells' own metabolic pathways, there are only a limited number of metabolic functions that antiviral drugs can target.
In contrast, bacteria are relatively large organisms, commonly reproduce by themselves outside of cells, and have many metabolic functions against which antibiotics can be directed.
Therefore, antiviral drugs are much more difficult to develop. Antiviral drugs can be toxic to human cells. Viruses can also develop resistance to antiviral drugs.
Research done by an Imperial College London team discovered the mechanism allowing Vaccinia virus to shed its outer lipid membrane and enter cells.
Viruses, such as influenza, are surrounded by a single lipid membrane, or envelope, and to enter cells this membrane must be removed.
Previously, all enveloped viruses were thought to shed their lipid membrane by fusion with a cell membrane, which allows the virus core to be released into the cell.
"This work has uncovered a completely novel biological process. It increases our understanding of how viruses can manipulate biological membranes and will help the development of new drugs against poxviruses," commented professor Geoffrey Smith, from >Imperial College London.
The extracellular form of Vaccinia virus has two lipid membranes, meaning a single fusion event will not release a naked virus core into the cell.
The researchers found that interactions between polyanionic or negatively charged molecules on the cell surface and glycoproteins on the virus particle caused a non-fusogenic disruption of the virus outer envelope, allowing the poxvirus to enter the cell.
As well as discovering how the double membrane problem is solved, the researchers demonstrated that polyionic compounds can be used to treat poxvirus infections, even days after infection has started.
Disrupting the outer membrane with polyanionic compounds exposes the virus, allowing antiviral antibodies to be more effective. The disruption of the outer membrane also limits the spread of the virus in the body.
The research is to be published in the >Proceedings of the National Academy of Sciences on 11 April.
