{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:29:28Z","timestamp":1790749768446,"version":"4.1.0"},"reference-count":11,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2011,10,1]],"date-time":"2011-10-01T00:00:00Z","timestamp":1317427200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antiviral Therapy"],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The National Research Council has recommended development of polio antiviral drugs to assist in management of outbreaks and to mitigate adverse consequences of vaccination. V-073 is a small molecule poliovirus capsid inhibitor that is being developed for these purposes. Antiviral use raises the potential of treatment-emergent resistance. Understanding virological consequences of resistance is important.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Six independent laboratory-derived V-073-resistant poliovirus variants were characterized for their ability to be neutralized by conventional vaccine-induced immune sera, to elicit serum neutralizing antibodies upon CD-1 mouse immunization, and to replicate in and to cause paralysis of TgPVR21 mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      V-073-resistant variants were effectively neutralized by oral poliovirus vaccine and inactivated poliovirus vaccine human immune sera. All variants elicited virus neutralizing antibody titres in CD-1 mice that were comparable to drug-susceptible parental and Sabin vaccine strain viruses. Infection efficiency of TgPVR21 mice by variants was comparable to (1 of 6 variants) or considerably lower than (5 of 6 variants) parental viruses. Drug-resistant variants replicated to levels comparable to (1 of 6 variants) or substantially less than (5 of 6 variants) their drug-susceptible parental viruses and were on average 1.4 log\n                      <jats:sub>10<\/jats:sub>\n                      (range 0.3 to &gt;2.8 log\n                      <jats:sub>10<\/jats:sub>\n                      ) less neurovirulent.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Laboratory-derived V-073-resistant variants exhibit clear attenuation of pathogenic properties while maintaining immunological features of drug-susceptible viruses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3851\/imp1838","type":"journal-article","created":{"date-parts":[[2011,6,30]],"date-time":"2011-06-30T14:21:49Z","timestamp":1309443709000},"page":"999-1004","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":19,"title":["Immunological and Pathogenic Properties of Poliovirus Variants Selected for Resistance to Antiviral Drug V-073"],"prefix":"10.1177","volume":"16","author":[{"given":"Diana V","family":"Kouiavskaia","sequence":"first","affiliation":[{"name":"Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenia M","family":"Dragunsky","sequence":"additional","affiliation":[{"name":"Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Mei","family":"Liu","sequence":"additional","affiliation":[{"name":"Centers for Disease Control and Prevention, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Steven","family":"Oberste","sequence":"additional","affiliation":[{"name":"Centers for Disease Control and Prevention, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc S","family":"Collett","sequence":"additional","affiliation":[{"name":"ViroDefense, Inc., Rockville, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin M","family":"Chumakov","sequence":"additional","affiliation":[{"name":"Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2011,10,1]]},"reference":[{"key":"bibr1-IMP1838","unstructured":"Committee on Development of a Polio Antiviral and its Potential Role in Global Poliomyelitis Eradication, National Research Council. Exploring the role of antiviral drugs in the eradication of polio: workshop report. Washington: The National Academies Press 2006. (Accessed 14 June 2011.) Available from http:\/\/www.nap.edu\/catalog\/php?record_id=11599."},{"key":"bibr2-IMP1838","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00671-09"},{"key":"bibr3-IMP1838","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.6.1220"},{"key":"bibr4-IMP1838","unstructured":"World Health Organization. Manual for the virological investigation of polio. WHO\/EPI\/GEN\/97.01. Geneva: World Health Organization 1997. (Accessed 14 June 2011.) Available from http:\/\/whqlibdoc.who.int\/hq\/1997\/WHO_EPI_GEN_97.01.pdf."},{"key":"bibr5-IMP1838","first-page":"497","volume":"71","year":"1993","journal-title":"Bull World Health Organ"},{"key":"bibr6-IMP1838","unstructured":"Committee for the Update of the Guide for the Care and Use of Laboratory Animals, National Research Council. Guide for the care and use of laboratory animals. 8th ed. Washington: National Academies Press 2010. (Accessed 14 June 2011.) Available from http:\/\/www.nap.edu\/catalog.php?record_id=12910."},{"key":"bibr7-IMP1838","doi-asserted-by":"publisher","DOI":"10.1016\/j.jviromet.2005.01.030"},{"key":"bibr8-IMP1838","doi-asserted-by":"publisher","DOI":"10.1016\/j.jviromet.2010.07.037"},{"key":"bibr9-IMP1838","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90168-E"},{"key":"bibr10-IMP1838","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.3.951"},{"key":"bibr11-IMP1838","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/166.4.747"}],"container-title":["Antiviral Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP1838","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP1838","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T12:50:17Z","timestamp":1777380617000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3851\/IMP1838"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,10]]},"references-count":11,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2011,10]]}},"alternative-id":["10.3851\/IMP1838"],"URL":"https:\/\/doi.org\/10.3851\/imp1838","relation":{},"ISSN":["1359-6535","2040-2058"],"issn-type":[{"value":"1359-6535","type":"print"},{"value":"2040-2058","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,10]]}}}