PD 404,182 is a virucidal small molecule that disrupts hepatitis C virus and human immunodeficiency virus
We describe a virucidal small molecule, PD 404,182, effective against hepatitis C virus (HCV) and human immunodeficiency virus (HIV). The median IC50 values for the antiviral effect of PD 404,182 against HCV and HIV in cell culture are 11 μM and 1 μM, respectively. The antiviral activity of PD 404,182 is due to physical disruption of virions that is accompanied to varying degrees (depending on the virus and exposure temperature/time) by release of viral nucleic acids into the surrounding medium. PD 404,182 does not directly lyse liposomal membranes even after extended exposure and shows no attenuation in antiviral activity when pre-incubated with liposomes of various lipid compositions, suggesting that the compound inactivates viruses through interaction with a non-lipid structural component of the virus. The virucidal activity of PD 404,182 appears to be virus-specific as little to no viral inactivation was detected with the enveloped Dengue and Sindbis viruses. PD 404,182 effectively inactivates a broad range of primary isolates of HIV-1 as well as HIV-2 and simian immunodeficiency virus (SIV), and does not exhibit significant cytotoxicity with multiple human cell lines in vitro (CC50 > 300 μM). The compound is fully active in cervical fluids although exhibiting decreased potency in the presence of human serum, retains its full antiviral potency for over 8 h when in contact with cells and is effective against both cell-free and cell-associated HIV. These qualities make PD 404,182 an attractive candidate microbicide for the prevention of HIV transmission through sexual intercourse.
作 者：Ana Maria Chamouna, Karuppiah Chockalingama, Michael Bobardtc, Rudo Simeona, Jinhong Changd, Philippe Gallayc,1 and Zhilei Chena,b,1
期刊名称： Antimicrobial Agents and Chemotherapy
期卷页： 第卷 第期 页 原文链接：http://aac.asm.org/content/early/2011/11/10/AAC.05722-11.abstract?sid=d38ce85f-1954-474c-a963-c6564fa8a27a