Japanese researchers developed new molecules that prevent HIV from attacking immune cells.
HIV attacks immune cells, including T-helpers (T-lymphocytes), which the body needs to fight the virus off. The HIV particle first enters the T-helper cells, attaching to the CD4 protein on their surface. Once got inside, it creates copies of HIV using the cell division mechanism, and this ultimately kills the host cell. Many treatment methods, such as antiretroviral drugs, try to block the reproduction process, but finding a way to prevent HIV from attaching to CD4 is a very promising approach.
A team of researchers from Tokyo Medical and Dental University (TMDU) has created new molecules that prevent human immunodeficiency virus particles from attacking immune cells. This is accomplished by injecting compounds that mimic the CD4 protein. This new family of molecules acts as CD4 trap-proteins – HIV particles preferentially attach to fake molecules rather than to the cell surface.
In addition, scientists have found that adding polyethylene glycol (PEG) improves pharmacokinetics. “Hybrid molecules that mimic CD4 and also have a PEG-unit attached by a non-fissionable linker have shown better anti-HIV activity with lower cytotoxicity”, the first study author Takuya Kobayakawa says.
Thus, the created hybrids of low molecular CD4-mimetics with polyethylene glycol units act as inhibitors of HIV penetration.
Computer simulation carried out by the team of scientists has confirmed the hypothesis that the hybrid molecule works better because it can electrostatically interact with the carboxylate group of the virus. In animal tests, the hybrid molecule remained in the system longer than the parent compound. “These CD4-mimics have strong synergistic interactions with neutralizing antibodies to fight HIV”, the senior study author Professor Hirokazu Tamamura says. The study is published in the American Chemical Society’s Journal of Medicinal Chemistry.
This discovery has the potential to open the way to new treatments that are more effective to stop the spreading of HIV.
Eduard Yefimenko