In vitro anti-HIV and -HSV activity and safety of sodium rutin sulfate as a microbicide candidate.
Sodium rutin sulfate (SRS) is a sulfated rutin modified from the natural flavonol glycoside rutin. Here, we investigated its in vitro anti-HIV and -HSV activities and its cytotoxic profile. Fifty percent inhibitory concentration (IC(50)) values of SRS against HIV-1 X4 virus IIIB, HIV-1 R5 isolates Ada-M and Ba-L were 2.3+/-0.2, 4.5+/-2.0 and 8.5+/-3.8 microM with a selectivity index (SI) of 563, 575 and 329, respectively. Its IC(50) against primary R5 HIV-1 isolate from Yunnan province in China was 13.1+/-5.5 microM, with a SI of 197. In contrast, unsulfated rutin had no activity against any of the HIV-1 isolates tested. Further study indicated that SRS blocked viral entry and virus-cell fusion likely through interacting with the HIV-1 envelope glycoprotein. SRS also demonstrated some activity against human herpes simplex virus (HSV) with an IC(50) of 88.3+/-0.1 microM and a SI of 30. The 50% cytotoxicity concentration (CC(50)) of SRS was >3.0 mM, as determined in human genital ME180, HeLa and primary human foreskin fibroblast cells. Minimum inhibitory concentration of SRS for vaginal lactobacilli was >3.0 mM. These results collectively indicate that SRS represents a novel candidate for anti-HIV-1/HSV microbicide development.
Tao
Jian
J
Nanjing Agriculture University, 1 Weigang, Nanjing, Jiangsu 210095, China.
Hu
Qinxue
Q
Yang
Jing
J
Li
Rurun
R
Li
Xiuyi
X
Lu
Chengping
C
Chen
Chaoyin
C
Wang
Ling
L
Shattock
Robin
R
Ben
Kunlong
K
D000998:Antiviral Agents / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D002681:China; D005260:Female; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D048668:Lactobacillus delbrueckii / Q000187:drug effects; D012431:Rutin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D018139:Simplexvirus / Q000187:drug effects* / Q000502:physiology; D014621:Vagina / Q000187:drug effects / Q000382:microbiology; D053586:Virus Internalization / Q000187:drug effects
D000998:Antiviral Agents; C056067:rutin sulfate; D012431:Rutin