Today, a new paper published online by Nature, a leading academic journal, describes a new small-molecule drug developed by the biopharmaceutical company Gilead Sciences, demonstrating the potential for long-term treatment of HIV infection. Preliminary clinical studies showed that after a single dose of the drug, hiv-infected people had reduced viral load in the body, and the drug remained active in the body after more than 6 months of injection.
The study authors note in their paper that daily oral oral antiviral “cocktail” therapy provides a life-saving treatment for millions of people living with HIV, but some people are resistant to multiple drugs, reducing the effectiveness of the treatment. If, for some reason, patients are unable to adhere to daily medication, not only may the virus in the body return, but the risk of drug resistance will increase, not conducive to treatment.
Because of this, researchers are working to develop new long-acting drugs that give patients with HIV-resistant strains more treatment options, and can significantly reduce the frequency of medication, helping patients stick to treatment options.
AIDS has become a chronic disease that can be controlled by drugs, reducing the frequency of medication and helping patients stick to treatment (Photo: 123RF)
Before we introduce the drugs in this paper, let’s briefly introduce THE HIV virus. Among the virus particles, there is a unique cone protein shell called the HIV shell. The genome of the virus, along with reverse transcriptases and integration enzymes, is hidden in this shell. The shell is self-assembled by a shell protein that not only protects the genetic material of the virus, but also helps the virus’s genes and enzymes to fit perfectly at all stages of HIV infection, thus producing the virus continuously.
HIV shell made up of shell protein (Photo: PDB101.rcsb.org)
The study’s authors note that most small molecule antiviral drugs for HIV act by interfering with the virus’s reverse transcriptase or integrated enzymes, and that the new drug, called GS-6207, is a distinctive target. Designed to bind the HIV shell protein closely, this small molecule can interfere with the assembly of the shell and disrupt its function.
Inside the HIV virus, the integrity of the shell (magenta) is damaged by the combination of small molecules (cyan) proteins, and the HIV genome (white) cannot continue to be well wrapped together with reverse transcriptase (purple) and integration enzymes (blue) to support viral replication (Photo: Random42)
In cell experiments, the scientists found that the small molecule had a wide range of activity against more than 20 HIV strains tested, effectively inhibited the replication of the virus, and ec50 was 105 pM in MT-4 cells infected with HIV-1, making them more potent than other approved antiretroviral drugs. In addition, GS-6207 and other antiretroviral drugs can be used together to produce synergies, which researchers believe can be an ideal complement to “cocktail therapy.”
GS-6207 Molecular Structure
Next, the researchers conducted preliminary clinical trials. In a single-dose study of randomized, double-blind and placebo-controlled cases of 40 healthy individuals, the researchers showed overall safety and good tolerance by injecting the drug with subcutaneous injections. Moreover, GS-6207 showed slow, sustained drug release, with only one injection, and after more than six months the drug remained active in the body.
The researchers then conducted phase 1 clinical trials in 32 patients infected with HIV-1 but not treated. The results showed that after 9 days of single-dose administration, the viral load in the patient’s body decreased, although it was not completely removed.
In healthy people and HIV-1 infected people, the activity of this small molecule drug can be maintained for 24 weeks and reducethe viral load in the infected person
At the end of the paper, the researchers concluded that GS-6207, a first-in-class HIV-1 shell inhibitor, exhibited good safety, prolonged pharmacokinetic exposure, and the antiviral effects observed in humans, and could continue clinical development for long-term treatment of HIV infection. The study authors also said that because of the need for frequent administration, the small molecule drug could become a candidate for HIV prevention in risk groups, but that this needs to be tested in follow-up studies.
We look forward to positive results from subsequent clinical studies of this innovative treatment, which will ultimately benefit more people living with HIV-1.