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historical perspectives in the development of antiviral agents against poxviruses历史发展的视角疹病毒的抗病毒药物.pdf

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historical perspectives in the development of antiviral agents against poxviruses历史发展的视角疹病毒的抗病毒药物

Viruses 2010, 2, 1322-1339; doi:10.3390/v2061322 OPEN ACCESS viruses ISSN 1999-4915 /journal/viruses Review Historical Perspectives in the Development of Antiviral Agents Against Poxviruses Erik De Clercq Rega Institute for Medical Research, Department of Microbiology and Immunology, Minderbroedersstraat 10, B-3000 Leuven, Belgium; E-Mail: erik.declercq@rega.kuleuven.be; Tel.: +32-16-337367; Fax: +32-16-337340. Received: 19 April 2010; in revised form: 28 May 2010 / Accepted: 28 May 2010 / Published: 14 June 2010 Abstract: The poxvirus vaccinia virus (VV) served as the model virus for which the first antivirals, the thiosemicarbazones, were identified. This dates back to 1950; and, although there is at present no single antiviral drug specifically licensed for the chemotherapy or -prophylaxis of poxvirus infections, numerous candidate compounds have been described over the past 50 years. These compounds include interferon and inducers thereof (i.e., polyacrylic acid), 5-substituted 2’-deoxyuridines (i.e., idoxuridine), IMP dehydrogenase inhibitors, S-adenosylhomocysteine hydrolase inhibitors, acyclic nucleoside phosphonates (such as cidofovir) and alkoxyalkyl prodrugs thereof (such as CMX001), viral egress inhibitors (such as tecovirimat), and cellular kinase inhibitors (such as imatinib). Keywords: thiosemicarbazones; interferon (inducers); idoxuridine (IDU); acyclic nucleoside phosphonates; cidofovi