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In severe cases, it can lead to neurological complications such as acute flaccid myelitis (AFM). EV-D68 belongs to the enterovirus genera of the Picornaviridae family, which also includes many other significant human pathogens such as poliovirus, enterovirus A71, and rhinovirus. There are currently no vaccines or antivirals against EV-D68. In this review, we present the current understanding of the link between EV-D68 and AFM, the mechanism of viral replication, and recent progress in developing EV-D68 antivirals by targeting various viral proteins and host factors that are essential for viral replication. The future directions of EV-D68 antiviral drug discovery and the criteria for drugs to reach clinical trials are also discussed.<\/jats:p>","DOI":"10.1021\/acsinfecdis.0c00120","type":"journal-article","created":{"date-parts":[[2020,4,30]],"date-time":"2020-04-30T12:57:56Z","timestamp":1588251476000},"page":"1572-1586","source":"Crossref","is-referenced-by-count":80,"title":["Enterovirus D68 Antivirals: Past, Present, and Future"],"prefix":"10.1021","volume":"6","author":[{"given":"Yanmei","family":"Hu","sequence":"first","affiliation":[{"name":"The University of Arizona , , , ,","place":["Tucson, Arizona, United States, 85721"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rami","family":"Musharrafieh","sequence":"additional","affiliation":[{"name":"The University of Arizona , , , ,","place":["Tucson, Arizona, United States, 85721"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine","family":"Zheng","sequence":"additional","affiliation":[{"name":"The University of Arizona , , , ,","place":["Tucson, Arizona, United States, 85721"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4845-4621","authenticated-orcid":true,"given":"Jun","family":"Wang","sequence":"additional","affiliation":[{"name":"The University of Arizona , , , ,","place":["Tucson, Arizona, United States, 85721"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,4,30]]},"reference":[{"key":"2026081722191594600_cit1","doi-asserted-by":"publisher","first-page":"E12209","DOI":"10.1073\/pnas.1803347115","article-title":"Molecular basis\nfor the acid-initiated uncoating of\nhuman enterovirus D68","volume":"115","author":"Liu","year":"2018","journal-title":"Proc. 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