Researchers from Shandong University and colleagues presented the characterization of [I] as the most active compound from a series of novel diarypyridimine derivatives intended to overcome resistance to NNRTI-resistant HIV-1 strains. The compound displayed EC50 values of 0.0010 and 0.18 µM against HIV IIIB and RES056 strains, respectively.
Researchers from the U.S. National Institutes of Health and collaborators recently conducted a study investigating the mechanisms of HIV-1 resistance to integrase strand transfer inhibitors (INSTIs), such as the approved drug dolutegravir (DTG). They focused on understanding the mechanisms of resistance caused by mutations at positions 138, 140, and 148 and analyzed combinations of the mutations E138K, G140A/S, and Q148H/K/R, all conferring resistance to INSTIs.
It has gone unnoticed in HIV research until now, but a transcriptomic analysis has detected a molecule that could kill this virus. Scientists at a U.S. military research institute laboratory have found a common factor in human cells that inhibited the replication of HIV-1 in people living with the virus. “Without any manipulation of cells in people with HIV, we have found a host factor that is inhibiting HIV in vivo,” the senior author Rasmi Thomas, chief of the Laboratory of Integrative Multiomics at Walter Reed Army Institute of Research, told BioWorld. Using single cell RNA sequencing (scRNA-seq), the study published on Aug. 2, 2023, in Science Translational Medicine identified this host factor as prothymosin α, a protein isolated from the thymus in 1966 and described in 1984.
A study of the genetic determinants of HIV viral load in 3,879 people of African ancestries has found what is claimed to be the only new variant related to HIV infection discovered in more than two decades of research into how host genomics affects the response to the retrovirus.
Researchers from Laboratoire Biodim presented the discovery of novel HIV-1 integrase-LEDGF allosteric inhibitors (INLAIs), designed to share the binding site on the viral protein with the host factor LEDGF/p75. INLAIs act as molecular glues to promote hyper-multimerization of HIV-1 integrase protein to produce defective progeny virions, and as such, severely disrupt maturation of viral particles.
Although huge strides have been made with antiretroviral therapy (ART) and prevention since HIV was first reported 42 years ago, there is still not an effective preventive vaccine or a scalable cure for those living with HIV. But broadly neutralizing antibodies (bNAbs) look to be a further step down the pathway to a cure, speakers said during the International AIDS Society meeting held July 23 to 26 in Brisbane, Australia.
The HIV-1 envelope glycoprotein (Env) mediates cell entry and is the target of the host humoral immune response. Functional Env is a trimer of noncovalent gp120-gp41 heterodimers. Rational trimer design has transformed the HIV-1 vaccine research field and has helped understand Env structure and immunogenicity. Uncleaved prefusion-optimized (UFO) trimers have been shown to stabilize diverse HIV-1 Env glycoproteins.
Merck Sharp & Dohme Corp. researchers have patented targeted activator of cell kill (TACK) compounds acting as Gag polyprotein (HIV-1)/protein Pol dimerization inducers and thus reported to be useful for the treatment of HIV infection.
Although COVID-19 may be more severe in people with HIV (PWH), the underlying biological mechanisms among PWH treated with antiretroviral therapy (ART) remain largely unknown.
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