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For example, in addition to cellular cdks, PCIs could inhibit any of the herpesvirus-encoded kinases, DNA replication proteins, or proteins involved in nucleotide metabolism. To address this issue, we asked whether purine-derived PCIs (P-PCIs) inhibit HSV and HIV-1 replication by targeting cellular or viral proteins. P-PCIs inhibited replication of HSV-1 and -2 and HIV-1, which require cellular cdks to replicate, but not vaccinia virus or lymphocytic choriomeningitis virus, which are not known to require cdks to replicate. P-PCIs also inhibited strains of HSV-1 and HIV-1 that are resistant to conventional antiviral drugs, which target viral proteins. In addition, the anti-HSV effects of P-PCIs and a conventional antiherpesvirus drug, acyclovir, were additive, demonstrating that the two drugs act by distinct mechanisms. Lastly, the spectrum of proteins that bound to P-PCIs in extracts of mock- and HSV-infected cells was the same. Based on these observations, we conclude that P-PCIs inhibit virus replication by targeting cellular, not viral, proteins.<\/jats:p>","DOI":"10.1128\/jvi.76.15.7874-7882.2002","type":"journal-article","created":{"date-parts":[[2002,7,28]],"date-time":"2002-07-28T23:07:23Z","timestamp":1027897643000},"page":"7874-7882","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":98,"title":["Pharmacological Cyclin-Dependent Kinase Inhibitors Inhibit Replication of Wild-Type and Drug-Resistant Strains of Herpes Simplex Virus and Human Immunodeficiency Virus Type 1 by Targeting Cellular, Not Viral, Proteins"],"prefix":"10.1128","volume":"76","author":[{"given":"Luis M.","family":"Schang","sequence":"first","affiliation":[{"name":"University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Bantly","sequence":"additional","affiliation":[{"name":"University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Knockaert","sequence":"additional","affiliation":[{"name":"Station Biologique de Roscoff, CNRS, Roscoff, Bretagne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farida","family":"Shaheen","sequence":"additional","affiliation":[{"name":"University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Meijer","sequence":"additional","affiliation":[{"name":"Station Biologique de Roscoff, CNRS, Roscoff, Bretagne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Malim","sequence":"additional","affiliation":[{"name":"University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathanael S.","family":"Gray","sequence":"additional","affiliation":[{"name":"Genomics Institute of the Novartis Research Foundation, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscilla A.","family":"Schaffer","sequence":"additional","affiliation":[{"name":"University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.17.7904-7912.2001"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.200375297"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.20.5987"},{"key":"e_1_3_2_5_2","first-page":"2482","volume":"91","year":"1998","unstructured":"Arguello, F., M. 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