Structural bases of norovirus RNA dependent RNA polymerase inhibition by novel suramin-related compounds.
Structural bases of norovirus RNA dependent RNA polymerase inhibition by novel suramin-related compounds.
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DOI：
10.1371/journal.pone.0091765
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Hwu JR
中科院分区：
文献类型：
--
作者：
Croci R;Pezzullo M;Tarantino D;Milani M;Tsay SC;Sureshbabu R;Tsai YJ;Mastrangelo E;Rohayem J;Bolognesi M;Hwu JR
Noroviruses (NV) are +ssRNA viruses responsible for severe gastroenteritis; no effective vaccines/antivirals are currently available. We previously identified Suramin (9) as a potent inhibitor of NV-RNA dependent RNA polymerase (NV-RdRp). Despite significant in vitro activities versus several pharmacological targets, Suramin clinical use is hampered by pharmacokinetics/toxicity problems. To improve Suramin access to NV-RdRp in vivo, a Suramin-derivative, 8, devoid of two sulphonate groups, was synthesized, achieving significant anti-human-NV-RdRp activity (IC50 = 28 nM); the compound inhibits also murine NV (mNV) RdRp. The synthesis process led to the isolation/characterization of lower molecular weight intermediates (3–7) hosting only one sulphonate head. The crystal structures of both hNV/mNV-RdRps in complex with 6, were analyzed, providing new knowledge on the interactions that a small fragment can establish with NV-RdRps, and establishing a platform for structure-guided optimization of potency, selectivity and drugability.
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DOI：
10.1107/s0907444905036693
发表时间：
2006-01-01
影响因子：
2.2
作者：
Evans, P
通讯作者：
Evans, P
DOI：
10.1016/s1054-3589(08)60486-x
发表时间：
1978-01-01
期刊：
Advances in pharmacology and chemotherapy
影响因子：
--
作者：
Hawking, F
通讯作者：
Hawking, F
影响因子：
7.3
作者：
DUNN, PM;BLAKELEY, AGH
通讯作者：
BLAKELEY, AGH
影响因子：
--
作者：
Eltahla, Auda A.;Lackovic, Kurt;White, Peter A.
通讯作者：
White, Peter A.
影响因子：
5.9
作者：
KAPLAN, LD;WOLFE, PR;GOTTLIEB, MS
通讯作者：
GOTTLIEB, MS