Thursday, July 2, 2020

Gilead develops new HIV drug candidate

Reporter : Feng Lifei
Publisher : China Science News
Direct translation

Image : The picture shows the scene of the integrity of the HIV virus and the integrity of the capsid (magenta) under the action of small molecule (cyan) protein conjugates.The damaged capsid can no longer continue the HIV genome (white) and reverse transcriptase ( (Purple) and integrase (blue) are intact and cannot support virus replication. Image source: Random42/"Nature"
 

A brand new long-acting antiretroviral drug has demonstrated the potential to treat HIV infection. Preliminary clinical studies have shown that after a single dose of this drug is injected into HIV-infected people, the viral load in the body is reduced, and the drug remains active in the body more than 6 months after injection. Related research was published in Nature on July 1.

Daily oral antiretroviral is a way to control HIV infection, but some individuals become resistant to drugs, which weakens the treatment effect. The new long-acting drugs can increase the treatment options for patients with HIV-resistant strains in the body, and also help patients adhere to the treatment plan.

Stephen Yant and colleagues at Gilead, California, USA described a small molecule they developed called "GS-6207." GS-6207 can destroy the HIV capsid, the protein envelope that surrounds the viral genome. Based on past research, the author designed GS-6207 to tightly bind to the viral capsid protein, thereby interfering with the multiple interactions that are essential for viral replication.

In laboratory experiments, GS-6207 showed effective activity against multiple HIV strains, and could synergize with the approved antiretroviral drugs, making it an ideal supplement for combination therapy. According to a clinical study involving 40 healthy individuals, GS-6207—administered by injection—is generally safe, well tolerated, and remains active in the body more than 6 months after injection. A follow-up phase I clinical trial was conducted in 32 patients infected with HIV-1 but not treated. The results showed that after 9 days of treatment, the patient's viral load was reduced (but not completely cleared).

Most small molecule antiretroviral drugs used to treat HIV work by interfering with viral enzymes, but this latest discovery supports the treatment of HIV infection by targeting viral capsid proteins.

Yant et al said that this small molecule does not need to be frequently administered, so it may become a candidate drug for preventing HIV infection in risk groups, but this has not been tested in the current study.

Link to related article:

DOI: 10.1038/s41586-020-2443-1

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