eproducible and highly (EC 50 = 5?0 M). Furthermore, AZTTP proved to be a more robust assay, we have screened 100,000 compounds from the potent inhibitor of PERV RT than d4TTP. In contrast, 3TC, ChemBridge 2 (CB2) compound library at a low and high con- 4 -ethynyl-d4T, and the nonnucleoside RT inhibitor nevirapine centration against Inenza strain A/Udorn/72 (H3N2). The were inactive against PERV replication.?rate (>50% CPE inhibition of virus) for the compounds Conclusion: Some nucleoside HIV RT Salbutamol inhibitors, such as screened at 5 g/ml and 40 g/ml was determined to be 0.022% AZT, PMEO-DAPy, and PMPDAP, may be effective in the and 0.37%, respectively. The hits obtained in this screen were prevention of PERV transmission to humans upon xenotrans- evaluated by measuring their antiviral activity, cell toxicity and plantation. selectivity in dose response experiments. Three compounds dis- played moderate activity (SI 50 = 10?9) in reducing inenza doi: 10.1016/j.antiviral.2007.01.093 in the presence of 5 g/ml compound. Quite the opposite, when screening at the higher concentration, several compounds were 86 identid that were highly active with an SI 50 > 50.

These quanti- tative data provide a foundation for grouping the hits into classes of compounds with similar scaffolds for structure activity rela- tionship (SAR) analysis and make them excellent candidates for 17-AAG, an Hsp90 Inhibitor, Suppress Hepatitis C Virus (HCV) Replication Saneyuki Ujino 1 , ?, Kunitada Shimotohno 3 , Hiroshi Takaku 1 , 2 the development of new small-molecule therapeutics. Acknowledgement: This work was supported by contract NO1-AI-30047. 1 Department of Life and Environmental Sciences, Chiba, Japan; 2 High Technology Research Center, Chiba Institute of Tech- nology, 2-17-1 Tsudanuma Narashino, Chiba 275-0016, Japan; doi: 10.1016/j.antiviral.2007.01.092 3 Department of Viral Oncology, Institute for Virus Research, Kyoto University, Kyoto Salbutamol adrenergic receptor inhibitor 606-0507, Japan 85 Heat-shock protein 90 (Hsp90), which accounts for 1?% of Antiviral Activity of Reverse Transcriptase Inhibitors against Porcine Endogenous Retroviruses (PERV) Minyi Shi 1 , 2 , ?, Xin Wang 1 , Erik De Clercq 3 , Sonshin Takao 2 , cytosolic protein, is one of the most abundant cellular chap- erone proteins1. It functions in a multicomponent complex of chaperone proteins including Hsp70,

Hop (Hsp70 and Hsp90 organizing protein), Cdc37, Hsp40 and p23. Hsp90 is involved Masanori Baba 1 in the folding, activation and assembly of several proteins, 1 Center for Chronic Viral Diseases, Graduate School of Med- ical and Dental Sciences, Kagoshima University, Kagoshima, Japan; 2 Frontier Science Research Center, Kagoshima Univer- sity, Kagoshima, Japan; 3 Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium known as Hsp90 client proteins. As Salbutamol 51022-70-9 numerous oncoproteins have been shown to be Hsp90 client proteins, Hsp90 inhibitors have become a new strategy in antitumor therapy. Geldanamycin, a classical Hsp90 inhibitor, is known as a potent antitumor agent; however, it has not been used in clinical trials because of its liver toxicity.

17-Allylamino-17-demethoxygeldanamycin Background: Xenotransplantation is a possible solution to the (17-AAG) is a new derivative of geldanamycin that shares its shortage of organs in transplantation. The Kagoshima strain of important biological activities but shows less toxicity. mini-pigs is considered to be a suitable organ donor in xeno- Here, we present a new and potent strategy for the hepatitis transplantation because of its size and other favorable proes. C virus (HCV) therapy with 17-AAG, an Hsp90 sodium nitrate inhibitor. We However, a concern about the transmission of porcine endoge- examine the effects of 17-AAG on full length HCV replicon cells line. The HCV RNA replication in the HCV replicon was quan- 1 Program and Abstracts / Antiviral Research 74 (2007) A197 A63 tid by real time RT-PCR (Taq-Man) at 2 days with indicated dose (0.25 nM, 25 nM, 50 nM, an