A great deal of research revolves around the question of how does viruses replicate. Viruses since a very long time know to us, are held responsible for various acute and chronicle diseases. Thus, it is crucial to know the in and out of viruses. According to recent research at Colorado State University they have used computational chemistry, biochemistry and virology to uncover new information on how viruses replicate. The observed, that these viruses paralyze their own genome replication machinery.
The study, “Motif V regulates energy transduction between the flavivirus NS3 ATPase and RNA-binding cleft,” was published in the Journal of Biological Chemistry on Feb. 7.
Nonstructural Protein 3 – or NS3 – in flaviviruses has been the topic of study for Kelly Du Pont, the first author of the study and a doctoral candidate in chemistry at CSU, studies. She observed NS3 causes a number of diseases in humans. NS3 is a key enzyme that these viruses use to copy their genomes.
For flaviviruses to replicate, the NS3 helicase – a viral enzyme that binds or remodels nucleic acid – has to unwind the double-stranded ribonucleic acid. NS3 uses adenosine triphosphate or ATP, a molecule abundant in cells, as fuel to power the unwinding.
Du Pont said this research was initially focused on trying to figure out what part of the NS3 protein acts as its molecular transmission. While studying the process, the team identified the part of NS3 that acts as a brake during unwinding.
They also identified mutations that make NS3 unwind the double-stranded ribonucleic acid faster than is normally seen, but also make the virus replicate more inefficiently in cells. If researchers can learn more about how NS3 unwinds the double-stranded ribonucleic acid and how this process is controlled, they could potentially target areas within the helicase for the development of drugs to treat virus-caused diseases.
“Most vaccines are developed by finding random mutations that slow down virus growth,” he said. “By understanding how viral enzymes like NS3 work in great detail, we can use that information to rationally design new mutant viruses that replicate less well and act better as a vaccine, without having to rely on chance to make the vaccine. This can help develop vaccines more rapidly and precisely.”
The research team is now taking a closer look at how changes in NS3 affect replication of the virus and how the changes affect the ability of the virus to kill cells.
Source: Colorado State University