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dc.contributor.authorWhite, Judith M
dc.contributor.authorSchiffer, Joshua T
dc.contributor.authorBender Ignacio, Rachel A
dc.contributor.authorXu, Shuang
dc.contributor.authorKainov, Denis
dc.contributor.authorIanevski, Aleksandr
dc.contributor.authorAittokallio, Tero
dc.contributor.authorFrieman, Matthew
dc.contributor.authorOlinger, Gene G
dc.contributor.authorPolyak, Stephen J
dc.date.accessioned2022-01-19T16:05:07Z
dc.date.available2022-01-19T16:05:07Z
dc.date.issued2021-12-21
dc.identifier.urihttp://hdl.handle.net/10713/17593
dc.description.abstractThe world was unprepared for coronavirus disease 2019 (COVID-19) and remains ill-equipped for future pandemics. While unprecedented strides have been made developing vaccines and treatments for COVID-19, there remains a need for highly effective and widely available regimens for ambulatory use for novel coronaviruses and other viral pathogens. We posit that a priority is to develop pan-family drug cocktails to enhance potency, limit toxicity, and avoid drug resistance. We urge cocktail development for all viruses with pandemic potential both in the short term (<1 to 2 years) and longer term with pairs of drugs in advanced clinical testing or repurposed agents approved for other indications. While significant efforts were launched against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in vitro and in the clinic, many studies employed solo drugs and had disappointing results. Here, we review drug combination studies against SARS-CoV-2 and other viruses and introduce a model-driven approach to assess drug pairs with the highest likelihood of clinical efficacy. Where component agents lack sufficient potency, we advocate for synergistic combinations to achieve therapeutic levels. We also discuss issues that stymied therapeutic progress against COVID-19, including testing of agents with low likelihood of efficacy late in clinical disease and lack of focus on developing virologic surrogate endpoints. There is a need to expedite efficient clinical trials testing drug combinations that could be taken at home by recently infected individuals and exposed contacts as early as possible during the next pandemic, whether caused by a coronavirus or another viral pathogen. The approach herein represents a proactive plan for global viral pandemic preparedness.en_US
dc.description.urihttps://doi.org/10.1128/mbio.03347-21en_US
dc.language.isoenen_US
dc.publisherAmerican Society for Microbiologyen_US
dc.relation.ispartofmBioen_US
dc.subjectCOVID-19en_US
dc.subjectEbola virusen_US
dc.subjectSARS-CoV-2en_US
dc.subjectantiviral drugsen_US
dc.subjectcategory A-C pathogensen_US
dc.subjectcountermeasuresen_US
dc.subjectdrug synergyen_US
dc.subjectearly treatmenten_US
dc.subjectmodel-driven approachen_US
dc.subjectpandemic preparednessen_US
dc.subjectprophylaxisen_US
dc.subjectviral pandemicen_US
dc.titleDrug Combinations as a First Line of Defense against Coronaviruses and Other Emerging Viruses.en_US
dc.typeArticleen_US
dc.identifier.doi10.1128/mbio.03347-21
dc.identifier.pmid34933447
dc.source.journaltitlemBio
dc.source.volume12
dc.source.issue6
dc.source.beginpagee0334721
dc.source.endpage
dc.source.countryUnited States


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