Researchers Synthesized And Tested The Anti-HIV Activity of A molecule That Mimics CD4

A team of scientists led by the Institute of Biomaterials and Bioengineering at Tokyo Medical and Dental University (TMDU) has created a new molecule that prevents human immunodeficiency virus (HIV) particles from attacking immune cells. This is achieved by injecting compounds that mimic the proteins normally used by viruses to enter cells. This work may lead to new HIV treatments that may be more effective in preventing the proliferation of the virus with fewer side effects.

HIV is a very dangerous pathogen because it attacks the immune cells that the body needs to fight back, including T helper cells. HIV particles first enter the T helper cells by attaching to the CD4 protein on their surface. Once inside, the reproduction mechanism of T helper cells will be hijacked to replicate HIV and ultimately kill the host cell. Many treatments, such as antiretroviral drugs, try to prevent this reproduction process, but it would be better to find a way to prevent HIV from attaching first.

Now, a team of researchers led by Tokyo Medical and Dental University (TMDU) has created a new family of molecules that can act as bait CD4 proteins. HIV particles preferentially attach to the pseudo-molecules rather than to the cell surface. Scientists have discovered that adding polyethylene glycol (PEG) can improve pharmacokinetics. "Mixed molecules that mimic CD4 and also have PEG units attached to non-cleavable linkers show better anti-HIV activity and lower cytotoxicity," said first author Takuya Kobayakawa.

The computer simulations that the team ran support the hypothesis that the mixed molecule works better because it can electrostatically interact with the carboxyl groups on the virus. In the test on rhesus monkeys, the hybrid molecules stayed longer in the system than the parent compound. "These CD4 mimics have a strong synergistic interaction with neutralizing antibodies against HIV," said senior author Hirokazu Tamamura. It is possible to develop new combination therapies to help utilize the new molecules. This work was published in the "Journal of Medicinal Chemistry" under the title "a mixture of small molecule CD4 mimics and polyethylene glycol units as HIV entry inhibitors."

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