Fighting HIV. We've got something new

Recently, science, a leading academic journal, published two papers online, introducing two recent developments in the fight against HIV infection The first paper describes why commonly used anti HIV drugs are effective, and the second describes why these drugs sometimes fail Before introducing these two papers, let's introduce HIV In this virus, there is a protein complex called an integrase, which contains the DNA of the virus and a protein called an integrase After entering the cell, a series of reactions will integrate the genetic material of the virus into human DNA and generate new viruses continuously At present, scientists have developed a series of drugs that can inhibit the integron, which are called integrated enzyme chain transfer inhibitors (insti), which can prevent the integron from integrating the virus DNA into the human genome, so as to control the disease Although it has achieved good clinical efficacy, so far we do not know the specific mode of action of these drugs, and do not know why sometimes HIV virus will develop drug resistance against these drugs The first study, led by scientists at the Salk Institute, answered the previous question Previously, scientists have been unable to isolate the whole body from the HIV virus, so most of them are prototype foamy virus (PFV), which is closely related to HIV In this paper, the researchers have separated the purified HIV virus integron, and obtained the structure of the integron with the approved insti drug or with the drug under research by using single particle cryo-EM From the structure, the scientists observed that compared with the structure previously obtained in PFV, HIV integrant and drug binding way is significantly different For example, a kind of in-depth therapy called 4f, although it can well integrate PFV, it can not well integrate HIV This also shows that drugs developed on the basis of PFV integrant may not be suitable for HIV infection Another key finding is that these insti drugs recognize exactly where the integron binds to DNA In other words, if there is a mutation in this position, so that the drug can not be combined, it is likely that the HIV integration lost the ability to combine DNA, thus losing its ability to invade the human body "We're looking at drugs that are already in clinical use, or molecules that are under development Before this paper, no one knew how they combined with this complex of HIV, "said Professor Dmitry lyumkis, the study's co-author." a better understanding of how these drugs work can help us optimize them and design new drugs " The second study was from Harvard University and the Francis Crick Institute The scientists used a primate lentivirus similar to HIV-1, and also used frozen electron microscopy to obtain the structure of its integrase when combined with drugs Through this structure, scientists found that the reason why these drugs have strong binding ability is that they can bond with metal ions on integrase However, some resistant virus strains will change the environment around metal ions, which will weaken the binding ability of drugs "We found that HIV can slightly change the chemical environment around metal ions and weaken the binding ability of drugs This is a gap in the armor of these drugs, "said Professor Peter cherepanov, one of the study's co authors "The good news is that we have finally seen the precise structure of the active site of viral enzyme and drug binding These blueprints can guide the design of more effective integrase inhibitors, which are expected to improve the quality of life of millions of people living with HIV " Professor Alan Engelman, another corresponding author of the study, commented All in all, these two structural biology studies have brought us new insights to fight HIV infection We also hope that with the help of these models, researchers can develop more and better anti infective drugs for the benefit of patients all over the world! (BIOON Com)