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dc.contributor.authorBerry, Michael
dc.contributor.authorFielding, Burtram C.
dc.contributor.authorGamieldien, Junaid
dc.date.accessioned2017-02-28T11:03:47Z
dc.date.available2017-02-28T11:03:47Z
dc.date.issued2015
dc.identifier.citationBerry, M. et al. (2015). Potential broad spectrum inhibitors of the coronavirus 3CLpro: a virtual screening and structure-based drug design study. Viruses,7: 6642–6660en_US
dc.identifier.issn1999-4915
dc.identifier.urihttp://hdl.handle.net/10566/2578
dc.identifier.urihttp://dx.doi.org/10.3390/v7122963
dc.description.abstractHuman coronaviruses represent a significant disease burden; however, there is currently no antiviral strategy to combat infection. The outbreak of severe acute respiratory syndrome (SARS) in 2003 and Middle East respiratory syndrome (MERS) less than 10 years later demonstrates the potential of coronaviruses to cross species boundaries and further highlights the importance of identifying novel lead compounds with broad spectrum activity. The coronavirus 3CLpro provides a highly validated drug target and as there is a high degree of sequence homology and conservation in main chain architecture the design of broad spectrum inhibitors is viable. The ZINC drugs-now library was screened in a consensus high-throughput pharmacophore modeling and molecular docking approach by Vina, Glide, GOLD and MM-GBSA. Molecular dynamics further confirmed results obtained from structure-based techniques. A highly defined hit-list of 19 compounds was identified by the structure-based drug design methodologies. As these compounds were extensively validated by a consensus approach and by molecular dynamics, the likelihood that at least one of these compounds is bioactive is excellent. Additionally, the compounds segregate into 15 significantly dissimilar (p < 0.05) clusters based on shape and features, which represent valuable scaffolds that can be used as a basis for future anti-coronaviral inhibitor discovery experiments. Importantly though, the enriched subset of 19 compounds identified from the larger library has to be validated experimentally.en_US
dc.language.isoenen_US
dc.publisherMDPIen_US
dc.subjectHuman coronavirusesen_US
dc.subjectMolecular dockingen_US
dc.subject3CLproen_US
dc.subjectVirtual screeningen_US
dc.subjectStructure-based drug designen_US
dc.subjectMolecular dynamicsen_US
dc.titlePotential broad spectrum inhibitors of the coronavirus 3CLpro: a virtual screening and structure-based drug design studyen_US
dc.typeArticleen_US
dc.description.accreditationISI
dcterms.rightsThis is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).


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