Measles virus entry inhibitors: a structural proposal for mechanism of action and the development of resistance.

ABSTRACT: Previously, we developed a panel of nonpeptidic compounds specifically preventing fusion of the measles virus (MV) with target cells at IC(50) values of 0.6-3 muM. Mutations in the MV fusion protein (MV F) that render resistance to these blockers were described. The structural basis for both inhibition and resistance was unclear in the earlier work because of the availability of a structural model for only the postfusion conformation of MV F. We have now developed structural models for both pre- and postfusion conformers of the latter protein trimer. The models allow investigation of the large-scale conformational changes occurring in the MV fusion machinery and, in conjunction with antisera binding studies, provide a rationale for how inhibitors may arrest a conformational intermediate by

SUBMITTER: Prussia AJ 

PROVIDER: S-EPMC4084900 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature