Researchers from Merck & Co. reported the development of MK-7762, a novel oxazolidine with antitubercular activity designed to overcome the off-target effects of linezolid.
Tuberculosis (TB) is a serious infectious disease caused by the bacterium Mycobacterium tuberculosis. While multidrug treatment regimens are the standard of care, the lengthy treatment schedule and the emergence of drug-resistant TB highlight the need for new therapeutic options to address these challenges. Inosine-5′-monophosphate dehydrogenase (GuaB) is vital for bacterial survival and propagation; therefore, GuaB inhibitors are considered potential compounds to add to first-line TB treatment.
An experimental tuberculosis (TB) vaccine with a dual mission – self-destruction after inducing immunity – improved the design of the Bacillus Calmette-Guérin (BCG) immunotherapy, a vaccine also used against cancer. Scientists at the University of Pittsburgh engineered this strain with a double break, which is effective and safer after an intravenous administration, according to their results in nonhuman primates and mice.
Tuberculosis still kills a lot of people worldwide (1.6 million deaths per year). Previous findings demonstrated that induced myeloid leukemia cell differentiation protein Mcl-1 inhibitors reduced the growth of Mycobacterium tuberculosis in human macrophages, but when inhibiting multiple proteins from the Mcl-1/Bcl-2 family, the result was more effective and in a more complex human in vitro granuloma environment.
Researchers from Michigan State University and Tarn Biosciences Inc. have published their work on the discovery and preclinical evaluation of novel antimycobacterial nitro-containing compounds.
One way to prevent the effect of a molecule is to use the cell’s own machinery to break it down. This is what the PROTAC technology does, an acronym for proteolysis targeting chimera, or BacPROTAC, when applied to bacteria. A study led by Austrian and German scientists has demonstrated the effectiveness of this technique in eliminating the tuberculosis pathogen Mycobacterium tuberculosis (Mtb). The finding opens the door to the BacPROTAC strategy as an alternative to the development of drugs against this microorganism.
Prior to the COVID-19 pandemic, tuberculosis ranked as the leading cause of infectious disease deaths worldwide; the increase of multidrug-resistant Mycobacterium tuberculosis puts some pressure on the search for new tuberculosis therapeutic approaches. Researchers from Sanofi SA and their collaborators have published preclinical results on a sequanamycin – sequanamycin 9 (SEQ-9) – for the potential treatment of tuberculosis.
Researchers at the University of Cape Town have compared the T-cell responses of individuals who were infected with Mycobacterium tuberculosis but were able to control the infection to those who developed active disease. The researchers wrote that the shared antigens in controllers “can be considered as high-priority targets for future vaccine development.” Their results were published online in Nature Medicine on Jan. 5, 2023. In their experiments, the team first sequenced the CDR3β region of the T-cell repertoire in a total of 166 individuals with M. tuberculosis infection who progressed to either TB or controlled infection.
GSK plc scientists seeking compounds with the potential to treat resistant tuberculosis infection identified a series of tetrazole agents using phenotypic screening against Mycobacterium tuberculosis.
