New Drug Target Found in HIV
Study targets how HIV avoids immune system defenses.
Iris-like pores in the capsid allows HIV to infect cells while avoiding detection from the immune system, a study published in Nature found.
For the study, researchers a hybrid approach that involved discerning the capsid’s atomic structure in different states and creating mutant versions of the virus to see how it altered the infection.
The results of the study showed that the iris-like pores in the capsid open and close like those in the eye. The pores suck in nucleotides at great speed that are need for the replication, while keeping out any unwanted molecules. This revealed why HIV is able to successful evade the immune system.
Once the capsid pores were identified, the team designed an inhibitor molecule that could block them called hexacarboxybenzene. They found that when the pores were blocked, the virus was unable to copy itself, resulting in it becoming non-infectious.
“We used to think that the capsid came apart as soon as the virus entered a cell but now realize that the capsid protects the virus from our innate immune system,” said senior study author Leo James. “The channels we’ve discovered explain how the fuel for replication gets into the capsid to allow the viral genome to be made.”
Although hexacarboxybenzene is unable to cross the cell membrane in human cells in order to gain access to the virus, researchers suggested that drugs may be designed in the future that can enter the cell.
Another option study authors suggest is to look at drugs that are currently on the market to treat HIV, called reverse transcriptase inhibitors.
“We have already designed a prototype inhibitor that directly targets the channel,” said lead study author David Jacques. “We predict that this feature may be common to other viruses and will be an attractive target for new antiviral drugs, including new treatments for HIV and related viruses.”