Shionogi & Co. Ltd. has disclosed heterocyclic derivatives characterized as reverse transcriptase/ribonuclease H (HIV-1) inhibitors for potential use in the treatment of HIV infection.
HIV-1 persistence in latent reservoirs of T lymphoid and myeloid origin is a major barrier for the cure of the disease, with complex and multifactorial mechanisms behind HIV-1 latency; thus, investigating these mechanisms is key for future targeted HIV therapies.
Many cases of human immunodeficiency virus (HIV)-1 infection can be effectively treated with existing drugs, but they can lose efficacy over time because of the emergence of resistance. In an effort to generate next-generation drugs, Chinese researchers at the Chinese Academy of Medical Sciences & Peking Union Medical College and other institutions synthesized a series of peptidomimetics against the viral protease, in which they extended the therapeutically effective hydroxyethyl sulfonamide scaffold using an amino acid linker. They reasoned that the linker could allow the drug to make additional contacts with the protease.
Merck Sharp & Dohme LLC (MSD) has synthesized new N-oxide derivative targeted activator of cell kill (TACK) compounds acting as Gag polyprotein (HIV-1)/protein Pol dimerization inducers reported to be useful for the treatment of HIV infection.
Nucleoside reverse transcriptase translocation inhibitors (NRTTIs) are a novel class of antiretroviral agents that inhibit HIV replication by targeting the viral reverse transcriptase enzyme and specifically blocking its translocation step during DNA synthesis, a critical process in the viral replication cycle.
It was previously demonstrated that the HIV-1 integrase (IN)-interacting host factor INI1/SMARCB1 binds to HIV-1 IN through its Rpt1 domain of INI1 (INI1-Rpt1) and plays a key role in assembly and particle production.
The development of an effective HIV vaccine remains an urgent public health need due to the high genetic variability and rapid mutation rates of the virus, which limit the generation of broadly neutralizing antibodies.
Antiretroviral therapy effectively suppresses HIV viral loads to undetectable levels but cannot eliminate the integration of viral DNA into the host cell genome.
HIV-1 infects lymphocytes and macrophages, gradually destroying the immune system. Multiple treatment combinations suppress the viral load to undetectable levels, but their long-term use leads to adverse effects. Allosteric inhibition of HIV-1 integrase has emerged as a source for new treatment strategies.
In mammals, the disruptor of telomeric silencing 1-like (DOT1L) is the only methyltransferase that catalyzes the mono-, di- and tri-methylation of histone H3 at lysine 79 (H3K79). The DOT1L/H3K79me is involved in several relevant physiological and pathological mechanisms, including several viral infections.
