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First generation inhibitors of the adenovirus proteinase.

ABSTRACT: As there are more than 50 adenovirus serotypes, the likelihood of developing an effective vaccine is low. Here we describe inhibitors of the adenovirus proteinase (AVP) with the ultimate objective of developing anti-adenovirus agents. Inhibitors were identified via structure-based drug design using as druggable sites the active site and a conserved cofactor pocket in the crystal structures of AVP. A lead compound was identified that had an IC50 of 18 ?M. One of eight structural derivatives of the lead compound had an IC50 of 140 nM against AVP and an IC50 of 490 nM against the AVP with its cofactor bound.

SUBMITTER: McGrath WJ

PROVIDER: S-EPMC3810942 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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First generation inhibitors of the adenovirus proteinase.

McGrath William J WJ Graziano Vito V Zabrocka Katarzyna K Mangel Walter F WF

FEBS letters 20130524 15

As there are more than 50 adenovirus serotypes, the likelihood of developing an effective vaccine is low. Here we describe inhibitors of the adenovirus proteinase (AVP) with the ultimate objective of developing anti-adenovirus agents. Inhibitors were identified via structure-based drug design using as druggable sites the active site and a conserved cofactor pocket in the crystal structures of AVP. A lead compound was identified that had an IC50 of 18 μM. One of eight structural derivatives of th ...[more]

PMID: 23711373

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