Antiviral effects of two Ganoderma lucidum triterpenoids against enterovirus 71 infection.
Enterovirus 71 (EV71) is a major causative agent for hand, foot and mouth disease (HFMD), and fatal neurological and systemic complications in children. However, there is currently no clinical approved antiviral drug available for the prevention and treatment of the viral infection. Here, we evaluated the antiviral activities of two Ganoderma lucidum triterpenoids (GLTs), Lanosta-7,9(11),24-trien-3-one,15;26-dihydroxy (GLTA) and Ganoderic acid Y (GLTB), against EV71 infection. The results showed that the two natural compounds display significant anti-EV71 activities without cytotoxicity in human rhabdomyosarcoma (RD) cells as evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation assay. The mechanisms by which the two compounds affect EV71 infection were further elucidated by three action modes using Ribavirin, a common antiviral drug, as a positive control. The results suggested that GLTA and GLTB prevent EV71 infection through interacting with the viral particle to block the adsorption of virus to the cells. In addition, the interactions between EV71 virion and the compounds were predicated by computer molecular docking, which illustrated that GLTA and GLTB may bind to the viral capsid protein at a hydrophobic pocket (F site), and thus may block uncoating of EV71. Moreover, we demonstrated that GLTA and GLTB significantly inhibit the replication of the viral RNA (vRNA) of EV71 replication through blocking EV71 uncoating. Thus, GLTA and GLTB may represent two potential therapeutic agents to control and treat EV71 infection.
State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
Wenjing
W
Zhang
State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
Junyan
J
Tao
State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
Xiaoping
X
Yang
Key Laboratory of Biodiversity and Biogeography, Kunming Institute of Botany, Chinese Academy of Science, Kunming 650201, China.
Zhuliang
Z
Yang
Department of Academy of Sciences, Liaoning University, Shenyang 110036, China.
Li
L
Zhang
Department of Academy of Sciences, Liaoning University, Shenyang 110036, China.
Hongsheng
H
Liu
State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
Kailang
K
Wu
State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: jwu@whu.edu.cn.
Jianguo
J
Wu
D000998:Antiviral Agents / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D029821:Enterovirus A, Human / Q000187:drug effects*; D004769:Enterovirus Infections / Q000188:drug therapy*; D006801:Humans; D020940:Reishi / Q000737:chemistry*; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
C000590174:15,26-dihydroxylanosta-7,9(11),24-trien-3-one; D000998:Antiviral Agents; D014315:Triterpenes; C000590175:ganoderic acid Y
Antiviral activity; Enterovirus 71 (EV71); Ganoderma lucidum triterpenoids (GLTs); Hand-foot-mouth disease (HFMD); Potential therapeutic antiviral agents; Virus infection