Synthesis and Activity of Piperazine-containing Antirhinoviral Agents and Crystal Structure of SDZ 880-061 Bound to Human Rhinovirus 14

Oren, Deena A.; Zhang, Anqiang; Nesvadba, H.; Rosenwirth, Brigitte; Arnold, Edward

doi:10.1006/jmbi.1996.0307

Cited by 19 publications

(15 citation statements)

References 43 publications

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“…9), inhibited 85% (76/89) of HRV serotypes tested at concentrations 3 mg/mL. 136 Structural studies of SDZ 880-061 bound to HRV-14 reveal that this compound binds in the same hydrophobic pocket as previously discussed, leaving the innermost portion of the pocket vacant. 136 The alterations in VP1 backbone conformation are similar but less extensive, compared to other antiviral agents, such as SCH 38057 or WIN compounds.…”

Section: H Sdz 35-682 and Sdz 880-061mentioning

confidence: 94%

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Selective inhibitors of picornavirus replication

Palma

Vliegen

Clercq

et al. 2008

Medicinal Research Reviews

232

217

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Picornaviruses cover a large family of pathogens that have a major impact on human but also on veterinary health. Although most infections in man subside mildly or asymptomatically, picornaviruses can also be responsible for severe, potentially life-threatening disease. To date, no therapy has been approved for the treatment of picornavirus infections. However, efforts to develop an antiviral that is effective in treating picornavirus-associated diseases are ongoing. In 2007, Schering-Plough, under license of ViroPharma, completed a phase II clinical trial with Pleconaril, a drug that was originally rejected by the FDA after a New Drug Application in 2001. Rupintrivir, a rhinovirus protease inhibitor developed at Pfizer, reached clinical trials but was recently halted from further development. Finally, Biota's HRV drug BTA-798 is scheduled for phase II trials in 2008. Several key steps in the picornaviral replication cycle, involving structural as well as non-structural proteins, have been identified as valuable targets for inhibition. The current review aims to highlight the most important developments during the past decades in the search for antivirals against picornaviruses.

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Section: H Sdz 35-682 and Sdz 880-061mentioning

confidence: 94%

“…The marginal effect of SDZ 880-061 on uncoating is most probably due to the fact that it does not completely fill the hydrophobic pocket, hence not causing enough virion stabilization. 136 …”

Section: H Sdz 35-682 and Sdz 880-061mentioning

confidence: 97%

Selective inhibitors of picornavirus replication

Palma

Vliegen

Clercq

et al. 2008

Medicinal Research Reviews

232

217

View full text Add to dashboard Cite

show abstract

“…Binding of a piperazine to Rhinovirus B HRV14/SDZ 880-061 complex [50] was correctly reproduced with minimization of clashes, maximization of hydrophobic interactions and 2PHH. Binding of a piperazine to Rhinovirus B HRV14/SDZ 880-061 complex [50] was correctly reproduced with minimization of clashes, maximization of hydrophobic interactions and 2PHH.…”

Section: Software News and Updatesmentioning

confidence: 90%

GaudiMM: A modular multi‐objective platform for molecular modeling

et al. 2017

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GaudiMM (for Genetic Algorithms with Unrestricted Descriptors for Intuitive Molecular Modeling) is here presented as a modular platform for rapid 3D sketching of molecular systems. It combines a Multi-Objective Genetic Algorithm with diverse molecular descriptors to overcome the difficulty of generating candidate models for systems with scarce structural data. Its grounds consist in transforming any molecular descriptor (i.e. those generally used for analysis of data) as a guiding objective for PES explorations. The platform is written in Python with flexibility in mind: the user can choose which descriptors to use for each problem and is even encouraged to code custom ones. Illustrative cases of its potential applications are included to demonstrate the flexibility of this approach, including metal coordination of multidentate ligands, peptide folding, and protein-ligand docking. GaudiMM is available free of charge from https://github.com/insilichem/gaudi. © 2017 Wiley Periodicals, Inc.

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“…Thereby the molecules enter through a pore on the floor of the canyon. Correct shape, a certain flexibility, and predominantly hydrophobic character are requirements for binding [5]. The most prominent member of this class of antirhinoviral compounds, is pleconaril (WIN 63843), see Chart 1.…”

Section: Introductionmentioning

confidence: 99%

DockingVersus Pharmacophore Model Generation: A Comparison of High-Throughput Virtual Screening Strategies for the Search of Human Rhinovirus Coat Protein Inhibitors

Steindl

Langer

2005

QSAR Comb. Sci.

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Inhibition of the human rhinovirus coat protein is an intensively studied approach towards finding a therapy for common cold. We present the results of a docking study using the tool LigandFit and a database of 1000 drug-like compounds seeded with known active HRV coat protein inhibitors. One scoring function performed especially well in ranking the active molecules at high positions. The conformations and positions from the docking process were found to be in good agreement with the X-ray data. Furthermore, highly selective pharmacophore hypotheses were generated in a structure-based approach. They include information on necessary chemical functions as well as on the required shape. When applied in 3D database screening, they selectively retrieved compounds with known antirhinoviral activity from large data sets. We compare these two virtual screening methods and summarise their benefits but also the observed disadvantages. Finally, a focussed virtual library for a special class of rhinovirus coat protein inhibitors was generated with our novel tool ilib diverse and screened with the pharmacophore models described.

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Synthesis and Activity of Piperazine-containing Antirhinoviral Agents and Crystal Structure of SDZ 880-061 Bound to Human Rhinovirus 14

Cited by 19 publications

References 43 publications

Selective inhibitors of picornavirus replication

Selective inhibitors of picornavirus replication

GaudiMM: A modular multi‐objective platform for molecular modeling

DockingVersus Pharmacophore Model Generation: A Comparison of High-Throughput Virtual Screening Strategies for the Search of Human Rhinovirus Coat Protein Inhibitors

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