Host-directed therapies based on protease inhibitors to control Mycobacterium tuberculosis and HIV coinfection

Despite continuous and extensive global efforts in the fight against tuberculosis (TB), this infectious disease continues to exert a tremendous burden on public health concerns and deaths worldwide. TB, caused by the bacterial species Mycobacterium tuberculosis, is highly frequent in people living with HIV. The continuing epidemics of both chronic infections and the emergence of antimicrobial resistance, as well as the lack of effective diagnostic tools and drug–drug interactions, pose major challenges in the fight against these pathogens. Developing a wide range of host-directed therapies may improve treatment outcomes, helping alleviate the morbidity and mortality associated with both infections. In this review, we discuss the identification and development of new host-directed strategies based on protease inhibitors and their clinical relevance as adjunctive treatment. In the context of therapeutic agents with novel mechanisms, selective protease inhibitors, including saquinavir (SQV) and cystatins (CstC and CstF), are valuable targets that may provide effective therapeutic solutions for controlling Mtb and HIV coinfection.