1vrh
From Proteopedia
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HRV14/SDZ 880-061 COMPLEX
Overview
A series of antipicornaviral agents containing piperazinyl moieties was, synthesized with the objective of obtaining a compound with a broad, spectrum of antirhinovirus activity, high potency (< or = 0.003, microgram/ml), and low cytotoxicity (> or = 30 micrograms/ml). Five, compounds of this series were evaluated in detail for efficacy against, various HRV serotypes. The agent SDZ 880-061, containing the benzothiazine, moiety SDZ 108-075, which is particularly active against HRV14, and the, thiazolyl acetic acid ester group of SDZ 89-124, which is potent against, HRV1B, indeed has a relatively broad antiviral spectrum. SDZ 880-061, inhibited 85% of 89 HRV serotypes tested at a concentration of < or = 3, micrograms/ml. The 3.0 A resolution X-ray structure of SDZ 880-061 bound, to HRV14 has revealed the binding characteristics of this potent compound., It binds in the same pocket as other capsid-binding antiviral agents, characterized to date, leaving the innermost portion of the pocket vacant., The binding causes similar, although less extensive, alterations of the, HRV14 VP1 backbone conformation (residues 100 to 110, 151 to 159, and 213, to 224) compared to other antiviral agents analyzed structurally. Although, the contacts between SDZ 880-061 and HRV14 are mostly of hydrophobic, character, the inhibitor has three relatively short polar interactions, with residues of VP1 that represent potential hydrogen bonds. The amount, of solvent-accessible surface area of SDZ 880-061 buried in the complex, (613 A2) is within the range of that observed in protein-protein, interfaces. The observed influence of time of addition or removal of SDZ, 880-061 on virus yield and on the infectious-center formation indicates, that the compound primarily interferes with HRV14 cellular attachment., Since it is assumed that uncoating requires virion instability and/or, flexibility, the finding that SDZ 880-061 has only a marginal effect on, uncoating may be due to the fact that it does not completely fill the, hydrophobic pocket.
About this Structure
1VRH is a Protein complex structure of sequences from Human rhinovirus 10 with SD8 as ligand. Full crystallographic information is available from OCA.
Reference
Synthesis and activity of piperazine-containing antirhinoviral agents and crystal structure of SDZ 880-061 bound to human rhinovirus 14., Oren DA, Zhang A, Nesvadba H, Rosenwirth B, Arnold E, J Mol Biol. 1996 May 31;259(1):120-34. PMID:8648640
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