TY - JOUR
T1 - A simple, rapid, and sensitive system for the evaluation of anti-viral drugs in rats
AU - Li, Xiaoguang
AU - Qian, Hua
AU - Miyamoto, Fusako
AU - Naito, Takeshi
AU - Kawaji, Kumi
AU - Kajiwara, Kazumi
AU - Hattori, Toshio
AU - Matsuoka, Masao
AU - Watanabe, Kentaro
AU - Oishi, Shinya
AU - Fujii, Nobutaka
AU - Kodama, Eiichi N.
N1 - Funding Information:
This work was supported by a Grant from the Ministry of Education, Culture, Sports, Science, and Technology of Japan , a Grant for the Promotion of AIDS Research from the Ministry of Health, Labour and Welfare , a Grant for Research for Health Sciences Focusing on Drug Innovation from the Japan Health Sciences Foundation and the Science and Technology Incubation Program in Advanced Regions from the Japan Science and Technology Agency .
PY - 2012/7/27
Y1 - 2012/7/27
N2 - The lack of small animal models for the evaluation of anti-human immunodeficiency virus type 1 (HIV-1) agents hampers drug development. Here, we describe the establishment of a simple and rapid evaluation system in a rat model without animal infection facilities. After intraperitoneal administration of test drugs to rats, antiviral activity in the sera was examined by the MAGI assay. Recently developed inhibitors for HIV-1 entry, two CXCR4 antagonists, TF14016 and FC131, and four fusion inhibitors, T-20, T-20EK, SC29EK, and TRI-1144, were evaluated using HIV-1 IIIB and HIV-1 BaL as representative CXCR4- and CCR5-tropic HIV-1 strains, respectively. CXCR4 antagonists were shown to only possess anti-HIV-1 IIIB activity, whereas fusion inhibitors showed both anti-HIV-1 IIIB and anti-HIV-1 BaL activities in rat sera. These results indicate that test drugs were successfully processed into the rat sera and could be detected by the MAGI assay. In this system, TRI-1144 showed the most potent and sustained antiviral activity. Sera from animals not administered drugs showed substantial anti-HIV-1 activity, indicating that relatively high dose or activity of the test drugs might be needed. In conclusion, the novel rat system established here, " phenotypic drug evaluation" , may be applicable for the evaluation of various antiviral drugs in vivo.
AB - The lack of small animal models for the evaluation of anti-human immunodeficiency virus type 1 (HIV-1) agents hampers drug development. Here, we describe the establishment of a simple and rapid evaluation system in a rat model without animal infection facilities. After intraperitoneal administration of test drugs to rats, antiviral activity in the sera was examined by the MAGI assay. Recently developed inhibitors for HIV-1 entry, two CXCR4 antagonists, TF14016 and FC131, and four fusion inhibitors, T-20, T-20EK, SC29EK, and TRI-1144, were evaluated using HIV-1 IIIB and HIV-1 BaL as representative CXCR4- and CCR5-tropic HIV-1 strains, respectively. CXCR4 antagonists were shown to only possess anti-HIV-1 IIIB activity, whereas fusion inhibitors showed both anti-HIV-1 IIIB and anti-HIV-1 BaL activities in rat sera. These results indicate that test drugs were successfully processed into the rat sera and could be detected by the MAGI assay. In this system, TRI-1144 showed the most potent and sustained antiviral activity. Sera from animals not administered drugs showed substantial anti-HIV-1 activity, indicating that relatively high dose or activity of the test drugs might be needed. In conclusion, the novel rat system established here, " phenotypic drug evaluation" , may be applicable for the evaluation of various antiviral drugs in vivo.
KW - CXCR4 antagonist
KW - Fusion inhibitor
KW - HIV-1
KW - MAGI assay
KW - Rat
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U2 - 10.1016/j.bbrc.2012.06.097
DO - 10.1016/j.bbrc.2012.06.097
M3 - Article
C2 - 22735265
AN - SCOPUS:84864291198
SN - 0006-291X
VL - 424
SP - 257
EP - 261
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -
