US News & World Report (05.29.2013)
Researchers from the University of Pittsburgh School of Medicine used a supercomputer from the University of Illinois to map the structure of the protein that makes up the HIV capsid (the virus’s protein casing that holds its DNA). The capsid has to be strong enough to protect the virus outside of a host cell, but pliable enough to break open when the virus infects a cell so that the contents can be released for the virus to replicate in the host cells.
Scientists have tried to find ways to attack HIV’s capsid, but it has proved to be too tough. Now that The University of Illinois’s supercomputer, called “Blue Waters,” has been able to detail the chemical makeup and reveal “seams” in the capsid, scientists can use the information to find ways to take advantage of vulnerable areas of the virus. Peijun Zhang, one of the study authors, suggested that researchers now can work on two possible lines of therapy: they could try to make the capsid “hyperstable” or unable to separate or break open, thus rendering it harmless to humans; or they could make it less stable, destroying the virus before it had a chance to cause damage. The team discovered a three-helix bundle in the capsid that they felt could be a target for a drug.
HIV mutates very quickly, making it resistant to almost every antiviral drug. By targeting the capsid rather than its DNA, researchers believe the virus will not develop drug resistances as quickly. Zhang commented that most therapies target the virus’s reverse transcriptase, which is the process that allows it to reproduce. She felt that another strategy would be to develop drugs against the parts of the virus that do not mutate as much.
The full report, “Mature HIV-1 Capsid Structure by Cryo-Electron Microscopy and All-Atom Molecular Dynamics,” was published online in the journal Nature, (2013; doi:10.1038/nature12162).