Antiviral activities of 2,6-diaminopurine-based acyclic nucleoside phosphonates against herpesviruses: In vitro study results with pseudorabies virus (PrV, SuHV-1)

0463274 - BC 2017 RIV NL eng J - Článek v odborném periodiku
Zouharová, D. - Lipenská, I. - Fojtiková, M. - Kulich, P. - Neca, J. - Slaný, M. - Kovařčík, K. - Turanek-Knotigová, P. - Hubatka, F. - Celechovská, H. - Mašek, J. - Koudelka, Š. - Procházka, L. - Eyer, L. - Plocková, J. - Bartheldyová, E. - Miller, A. D. - Růžek, Daniel - Raška, M. - Janeba, Zlatko - Turánek, J.
Antiviral activities of 2,6-diaminopurine-based acyclic nucleoside phosphonates against herpesviruses: In vitro study results with pseudorabies virus (PrV, SuHV-1).
Veterinary Microbiology. Roč. 184, FEB 29 (2016), s. 84-93. ISSN 0378-1135. E-ISSN 1873-2542
Institucionální podpora: RVO:60077344 ; RVO:61388963
Klíčová slova: Pseudorabies * Acyclic nucleoside phosphonates * DNA viruses * Cidofovir * Antiviral drugs * DNA polymerase
Kód oboru RIV: EE - Mikrobiologie, virologie; CC - Organická chemie (UOCHB-X)
Impakt faktor: 2.628, rok: 2016

Pseudorabies virus (PrV), a causative agent of Aujeszky's disease, is deadly to most mammals with the exception of higher primates and men. This disease causes serious economic loses among farm animals, especially pigs, yet many European countries are today claimed to be Aujeszky's disease free because of the discovery of an efficient vaccination for pigs. In reality, the virus is still present in wild boar. Current vaccines are neither suitable for dogs nor are there anti-PrV drugs approved for veterinary use. Therefore, the disease still represents a high threat, particularly for expensive hunting dogs that can come into close contact with infected boars. Here we report on the anti-PrV activities of a series of synthetic diaminopurine-based acyclic nucleoside phosphonate (DAP-ANP) analogues. Initially, all synthetic DAP-ANPs under investigation are shown to exhibit minimal cytotoxicity by MTT and XTT tests (1-100 mu M range). Thereafter in vitro infection models are established using PrV virus SuHV-1, optimized on PK-15 and RK-13 cell lines. Out of the six DAP-ANP analogues tested, analogue VI functionalized with a cyclopropyl group on the 6-amino position of the purine ring proves the most effective antiviral DAP-ANP analogue against PrV infection, aided by sufficient hydrophobic character to enhance bioavailability to its cellular target viral DNA-polymerase. Four other DAP-ANP analogues with functional groups introduced to the C2'position are shown ineffective against PrV infection, even with favourable hydrophobic properties. Cidofovir (R), a drug approved against various herpesvirus infections, is found to exert only low activity against PrV in these same in vitro models.
Trvalý link: http://hdl.handle.net/11104/0262503