Researchers Develop Novel Molecules That Prevent HIV Particles From Attacking Immune Cells

April 21, 2021
Aislinn Antrim, Associate Editor

The molecules act as decoy CD4 proteins, which the HIV particles preferentially attach to instead of CD4 cells at the surface of the cell.

Investigators in Japan have developed novel molecules that prevent HIV particles from attacking immune cells, a finding that could potentially lead to new treatments that may be more effective at stopping the proliferation of the virus.

The danger of HIV lies in its ability to attack the immune cells necessary for the body to fight back, including T helper cells, according to a press release. HIV particles first gain entrance to a T helper cell by attaching to a CD4 protein on its surface. Once inside the cell, the reproduction machinery of the T helper cell is hijacked to make copies of HIV, ultimately killing the host cell.

Many treatments attempt to block this reproduction process, including antiretroviral drugs. However, the researchers said finding a way to prevent HIV from attaching in the first place would be a better, more efficient approach.

To investigate this further, a team of researchers at Tokyo Medical and Dental University created a new family of molecules that act as decoy CD4 proteins. According to the study, the HIV particles preferentially attach with the fake molecules instead of those at the surface of the cell. In their research, the investigators found that adding a polyethylene glycol (PEG) improved the pharmacokinetics of the treatment.

“Hybrid molecules that mimic CD4 and also have a PEG unit attached with an uncleavable linker showed better anti-HIV activity with lower cytotoxicity,” said first author Takuya Kobayakawa in a press release.

The investigators also ran computer simulations to confirm their findings, which supported their hypothesis that the hybrid molecule works better because it can interact electrostatically with a carboxylate group on the virus. In animal tests, the hybrid molecule remained in the system longer compared to the parent compound. Based on their findings, the investigators said new combined treatment protocols may be developed to take advantage of the new molecules.

“These CD4 mimics have strong synergistic interactions with neutralizing antibodies for fighting HIV,” said senior author Hirokazu Tamamura in the press release.

REFERENCE

HIV Has Been Had [news release]. Tokyo Medical and Dental University; January 27, 2021. https://www.tmd.ac.jp/english/press-release/20210127-1/. Accessed April 16, 2021