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dc.contributor.authorMatthew, Ashley N.
dc.contributor.authorLeidner, Florian
dc.contributor.authorLockbaum, Gordon J.
dc.contributor.authorHenes, Mina
dc.contributor.authorZephyr, Jacqueto
dc.contributor.authorHou, Shurong
dc.contributor.authorDesaboini, Nageswara Rao
dc.contributor.authorTimm, Jennifer
dc.contributor.authorRusere, Linah N.
dc.contributor.authorRagland, Debra A.
dc.contributor.authorPaulsen, Janet L.
dc.contributor.authorPrachanronarong, Kristina L.
dc.contributor.authorSoumana, Djade I.
dc.contributor.authorNalivaika, Ellen A.
dc.contributor.authorYilmaz, Nese Kurt
dc.contributor.authorAli, Akbar
dc.contributor.authorSchiffer, Celia A.
dc.date2022-08-11T08:08:26.000
dc.date.accessioned2022-08-23T15:55:03Z
dc.date.available2022-08-23T15:55:03Z
dc.date.issued2021-01-07
dc.date.submitted2021-01-27
dc.identifier.citation<p>Matthew AN, Leidner F, Lockbaum GJ, Henes M, Zephyr J, Hou S, Rao DN, Timm J, Rusere LN, Ragland DA, Paulsen JL, Prachanronarong K, Soumana DI, Nalivaika EA, Kurt Yilmaz N, Ali A, Schiffer CA. Drug Design Strategies to Avoid Resistance in Direct-Acting Antivirals and Beyond. Chem Rev. 2021 Jan 7. doi: 10.1021/acs.chemrev.0c00648. Epub ahead of print. PMID: 33410674. <a href="https://doi.org/10.1021/acs.chemrev.0c00648">Link to article on publisher's site</a></p>
dc.identifier.issn0009-2665 (Linking)
dc.identifier.doi10.1021/acs.chemrev.0c00648
dc.identifier.pmid33410674
dc.identifier.urihttp://hdl.handle.net/20.500.14038/29668
dc.description.abstractDrug resistance is prevalent across many diseases, rendering therapies ineffective with severe financial and health consequences. Rather than accepting resistance after the fact, proactive strategies need to be incorporated into the drug design and development process to minimize the impact of drug resistance. These strategies can be derived from our experience with viral disease targets where multiple generations of drugs had to be developed to combat resistance and avoid antiviral failure. Significant efforts including experimental and computational structural biology, medicinal chemistry, and machine learning have focused on understanding the mechanisms and structural basis of resistance against direct-acting antiviral (DAA) drugs. Integrated methods show promise for being predictive of resistance and potency. In this review, we give an overview of this research for human immunodeficiency virus type 1, hepatitis C virus, and influenza virus and the lessons learned from resistance mechanisms of DAAs. These lessons translate into rational strategies to avoid resistance in drug design, which can be generalized and applied beyond viral targets. While resistance may not be completely avoidable, rational drug design can and should incorporate strategies at the outset of drug development to decrease the prevalence of drug resistance.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=33410674&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1021/acs.chemrev.0c00648
dc.subjectDrug resistance
dc.subjectViruses
dc.subjectPeptides and proteins
dc.subjectGenetics
dc.subjectInhibitors
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectBiochemistry
dc.subjectMedicinal Chemistry and Pharmaceutics
dc.subjectMedicinal-Pharmaceutical Chemistry
dc.subjectPharmaceutics and Drug Design
dc.subjectVirus Diseases
dc.subjectViruses
dc.titleDrug Design Strategies to Avoid Resistance in Direct-Acting Antivirals and Beyond
dc.typeJournal Article
dc.source.journaltitleChemical reviews
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/1882
dc.identifier.contextkey21291269
html.description.abstract<p>Drug resistance is prevalent across many diseases, rendering therapies ineffective with severe financial and health consequences. Rather than accepting resistance after the fact, proactive strategies need to be incorporated into the drug design and development process to minimize the impact of drug resistance. These strategies can be derived from our experience with viral disease targets where multiple generations of drugs had to be developed to combat resistance and avoid antiviral failure. Significant efforts including experimental and computational structural biology, medicinal chemistry, and machine learning have focused on understanding the mechanisms and structural basis of resistance against direct-acting antiviral (DAA) drugs. Integrated methods show promise for being predictive of resistance and potency. In this review, we give an overview of this research for human immunodeficiency virus type 1, hepatitis C virus, and influenza virus and the lessons learned from resistance mechanisms of DAAs. These lessons translate into rational strategies to avoid resistance in drug design, which can be generalized and applied beyond viral targets. While resistance may not be completely avoidable, rational drug design can and should incorporate strategies at the outset of drug development to decrease the prevalence of drug resistance.</p>
dc.identifier.submissionpathfaculty_pubs/1882
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.contributor.departmentSchiffer Lab
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology


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