Structure-Driven Discovery of α,γ-Diketoacid Inhibitors Against UL89 Herpesvirus Terminase.

ABSTRACT: Human cytomegalovirus (HCMV) is an opportunistic pathogen causing a variety of severe viral infections, including irreversible congenital disabilities. Nowadays, HCMV infection is treated by inhibiting the viral DNA polymerase. However, DNA polymerase inhibitors have several drawbacks. An alternative strategy is to use compounds against the packaging machinery or terminase complex, which is essential for viral replication. Our discovery that raltegravir (1), a human immunodeficiency virus drug, inhibits the nuclease function of UL89, one of the protein subunits of the complex, prompted us to further develop terminase inhibitors. On the basis of the structure of 1, a library of diketoacid (α,γ-DKA and β,δ-DKA) derivatives were synthesized and tested for UL89-C nuclease activit

SUBMITTER: Bongarzone S 

PROVIDER: S-EPMC6645139 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature