Combinations of Drug Design for Anti-Mycobacterial Membrane

[摘要] To combat the increasing problem of medication resistance in human TB, new anti-tubercular medicines are urgently needed. Somestructure-assisted approaches to create drugs that target Mycobacterial Membrane Protein Large 3 (MmpL3) were employed. MmpL3 isrequired for the transfer of mycolic acids, a key component of mycobacterial cell walls. In cell culture, chemicals that effectively suppressthe development of Mycobacterium Tuberculosis (Mtb) and other mycobacteria were created. The structure of mycobacterial MmpL3 inassociation with one of these drugs (ST004) was determined using cryo-EM on lipid nanodiscs with an overall resolution of 3.36. Thestructure elucidates ST004's binding mechanism to MmpL3, with the S4 and S5 subsites of the inhibitor-binding pocket in the protontranslocation channel playing critical roles. These findings provide a potential foundation for the development of anti-tuberculosis medicinesthat target MmpL3. Nucleocapsid (N) protein has critical roles in the life cycle of Severe Acute Respiratory Syndrome CoronaVirus 2(SARS-CoV-2), including the production of Ribo Nucleo Protein (RNP) complex with the viral RNA.

[学科分类] 药理学