Molecular biologists from Yale have created an ultra-effective drug that suppresses the enzyme work that helps HIV integrate itself into the DNA of the cell, and protected it with mice from infection, according to an article published in the journal PNAS.
“One dose of nanoparticles stuffed with our” substance-1 “protected the T-cells of mice from mass death and kept the concentration of virus particles at a minimum level for three weeks.” Substance-1 “is able to combat both normal clinical strains of HIV and with its “invulnerable” versions, “- write Karen Anderson (Karen Anderson) and her colleagues from Yale University (USA).
As scientists explain, today, HIV patients can live decades after receiving antiretroviral drugs – substances that suppress various stages of viral replication in the cells of the body. Since they often have strong side effects, physicians often have to stop taking them for several weeks.
At the termination of their reception of a HIV “gets out of entrenchments” and starts to copy intensively itself, frequently returning to initial scales of an infection for three or two weeks. In recent years, scientists are actively trying to find drugs or antibodies that would help to avoid such a “counter-attack” of the virus, or allow “to drive” the virus out of the cells.
Anderson and her colleagues have been studying the structure of one of the main components of HIV, the so-called reverse transcriptase, for several years. It is a special enzyme that the virus uses to “read” its single RNA helix and turn it into a double strand of DNA that can be embedded in the genome of the infected cell.
Many types of antiretroviral drugs, as scientists explain, block the work of this protein, but none of them does it with 100% reliability and safety. Some of the viruses gradually become invulnerable to their action, and by themselves these substances have a number of deadly side effects that do not allow them to take them indefinitely.
Anderson and her colleagues were able to solve this problem by conducting most of the experiments not on real samples of cells and viruses, but on their virtual counterparts. Using computer models of different versions of reverse transcriptase, scientists studied how different substances and drugs already known to science interact with it, and selected the most effective ones.
Having discovered several dozens of such molecules capable of suppressing the work of this enzyme, scientists tried to improve their work by changing the structure of their key elements, which are connected with reverse transcriptase. The fruit of these efforts was the discovery of a molecule, called “substance-1”, interacting with the virus about 2,5 thousand times more actively than its ancestor.
Having achieved this result, scientists synthesized its real analogue and tested its work on cultures of immune cells infected with HIV, in combination with other antiretroviral drugs or in the composition of special nanoparticles, which gradually separated “substance-1” into the environment.
As these experiments showed, “substance-1” strengthened the action of other drugs and effectively suppressed the multiplication of the virus, even in small doses, without causing any side effects, which led scientists to proceed to the preclinical tests that they conducted in mice with a “human” immune system.
These experiments showed that even a single dose of nanoparticles with “substance-1” protected the mice from infection for 30 days, if they were not infected before the experiments, and kept it at a minimally low level otherwise. All this, according to scientists, suggests that this compound can become the basis for safe and “long-playing” drugs and means of prevention from HIV.