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dc.contributor.authorAli, Akbar
dc.contributor.authorBandaranayake, Rajintha M.
dc.contributor.authorCai, Yufeng
dc.contributor.authorKing, Nancy M.
dc.contributor.authorKolli, Madhavi
dc.contributor.authorMittal, Seema
dc.contributor.authorFoulkes-Murzycki, Jennifer E.
dc.contributor.authorNalam, Madhavi N. L.
dc.contributor.authorNalivaika, Ellen A.
dc.contributor.authorOzen, Aysegul
dc.contributor.authorPrabu-Jeyabalan, Moses
dc.contributor.authorThayer, Kelly
dc.contributor.authorSchiffer, Celia A.
dc.date2022-08-11T08:08:00.000
dc.date.accessioned2022-08-23T15:38:46Z
dc.date.available2022-08-23T15:38:46Z
dc.date.issued2010-11-14
dc.date.submitted2011-11-22
dc.identifier.citationViruses. 2010 Nov;2(11):2509-2535. <a href="http://dx.doi.org/10.3390/v2112509">Link to article on publisher's site</a>
dc.identifier.issn1999-4915 (Linking)
dc.identifier.doi10.3390/v2112509
dc.identifier.pmid21994628
dc.identifier.urihttp://hdl.handle.net/20.500.14038/26006
dc.description<p>Co-author Aysegul Ozen is a student in the Biochemistry & Molecular Pharmacology program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.</p>
dc.description.abstractHIV-1 protease is one of the major antiviral targets in the treatment of patients infected with HIV-1. The nine FDA approved HIV-1 protease inhibitors were developed with extensive use of structure-based drug design, thus the atomic details of how the inhibitors bind are well characterized. From this structural understanding the molecular basis for drug resistance in HIV-1 protease can be elucidated. Selected mutations in response to therapy and diversity between clades in HIV-1 protease have altered the shape of the active site, potentially altered the dynamics and even altered the sequence of the cleavage sites in the Gag polyprotein. All of these interdependent changes act in synergy to confer drug resistance while simultaneously maintaining the fitness of the virus. New strategies, such as incorporation of the substrate envelope constraint to design robust inhibitors that incorporate details of HIV-1 protease's function and decrease the probability of drug resistance, are necessary to continue to effectively target this key protein in HIV-1 life cycle.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=21994628&dopt=Abstract">Link to Article in PubMed</a>
dc.subjectDrug Resistance, Viral
dc.subjectHIV Antigens
dc.subjectHIV Protease Inhibitors
dc.subjectHIV-1
dc.subjectHumans
dc.subjectVirus Replication
dc.subjectgag Gene Products, Human Immunodeficiency Virus
dc.subjectImmunology and Infectious Disease
dc.subjectMolecular Biology
dc.subjectVirology
dc.titleMolecular Basis for Drug Resistance in HIV-1 Protease
dc.typeJournal Article
dc.source.journaltitleViruses
dc.source.volume2
dc.source.issue11
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1136&amp;context=bmp_pp&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/bmp_pp/136
dc.identifier.contextkey2367986
refterms.dateFOA2022-08-23T15:38:46Z
html.description.abstract<p>HIV-1 protease is one of the major antiviral targets in the treatment of patients infected with HIV-1. The nine FDA approved HIV-1 protease inhibitors were developed with extensive use of structure-based drug design, thus the atomic details of how the inhibitors bind are well characterized. From this structural understanding the molecular basis for drug resistance in HIV-1 protease can be elucidated. Selected mutations in response to therapy and diversity between clades in HIV-1 protease have altered the shape of the active site, potentially altered the dynamics and even altered the sequence of the cleavage sites in the Gag polyprotein. All of these interdependent changes act in synergy to confer drug resistance while simultaneously maintaining the fitness of the virus. New strategies, such as incorporation of the substrate envelope constraint to design robust inhibitors that incorporate details of HIV-1 protease's function and decrease the probability of drug resistance, are necessary to continue to effectively target this key protein in HIV-1 life cycle.</p>
dc.identifier.submissionpathbmp_pp/136
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.source.pages2509-2535


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