tetano
Editor, Senior Moderator
Antimicrob Agents Chemother. 2013 Jul 8. [Epub ahead of print]
Identification of 23-(S)-2-Amino-3-Phenylpropanoyl-Silybin as an Antiviral Agent for Influenza A Virus Infection in Vitro and in Vivo.
Dai JP, Wu LQ, Li R, Zhao XF, Wan QY, Chen XX, Li WZ, Wang GF, Li KS.
Source
Department of Microbiology and Immunology, Shantou University Medical College, Shantou, Guangdong, 515041, P. R. China.
Abstract
It has been reported that autophagy is involved in the replication of many viruses. In this study, we screened 89 medicinal plants using an assay based on the inhibition of the formation of the Atg12-Atg5/Atg16 heterotrimer, an important regulator of autophagy, and selected Silybum marianum L. for further study. An antiviral assay indicated that silybin, the major active compound of Silybum marianum L., can inhibit IAV infection. We later synthesized 5 silybin derivatives and found that 23-(S)-2-amino-3- phenylpropanoyl- silybin (S3) had the best activity. When we compared the polarity of the substituent groups, we found that the hydrophobicity of the substituent groups was positively correlated with their activities. We further studied the mechanisms of action of these compounds and determined that S0 and S3 also inhibited both the formation of the Atg12-Atg5/Atg16 heterotrimer and the elevated autophagy induced by IAV infection. In addition, we found that S0 and S3 could inhibit several components induced by IAV infection, including oxidative stress, the activation of ERK/p38 MAPK and IKK pathways, and the expression of autophagic genes, especially Atg7 and Atg3; all of these components have been reported to be related to the formation of the Atg12-Atg5/Atg16 heterotrimer, which might validate our screening strategy. Finally, we demonstrated that S3 can significantly reduce influenza virus replication and the associated mortality in infected mice. In conclusion, we identified 23-(S)-2-amino-3- phenylpropanoyl- silybin as a promising inhibitor of IAV infection.
PMID:
23836164
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23836164
Identification of 23-(S)-2-Amino-3-Phenylpropanoyl-Silybin as an Antiviral Agent for Influenza A Virus Infection in Vitro and in Vivo.
Dai JP, Wu LQ, Li R, Zhao XF, Wan QY, Chen XX, Li WZ, Wang GF, Li KS.
Source
Department of Microbiology and Immunology, Shantou University Medical College, Shantou, Guangdong, 515041, P. R. China.
Abstract
It has been reported that autophagy is involved in the replication of many viruses. In this study, we screened 89 medicinal plants using an assay based on the inhibition of the formation of the Atg12-Atg5/Atg16 heterotrimer, an important regulator of autophagy, and selected Silybum marianum L. for further study. An antiviral assay indicated that silybin, the major active compound of Silybum marianum L., can inhibit IAV infection. We later synthesized 5 silybin derivatives and found that 23-(S)-2-amino-3- phenylpropanoyl- silybin (S3) had the best activity. When we compared the polarity of the substituent groups, we found that the hydrophobicity of the substituent groups was positively correlated with their activities. We further studied the mechanisms of action of these compounds and determined that S0 and S3 also inhibited both the formation of the Atg12-Atg5/Atg16 heterotrimer and the elevated autophagy induced by IAV infection. In addition, we found that S0 and S3 could inhibit several components induced by IAV infection, including oxidative stress, the activation of ERK/p38 MAPK and IKK pathways, and the expression of autophagic genes, especially Atg7 and Atg3; all of these components have been reported to be related to the formation of the Atg12-Atg5/Atg16 heterotrimer, which might validate our screening strategy. Finally, we demonstrated that S3 can significantly reduce influenza virus replication and the associated mortality in infected mice. In conclusion, we identified 23-(S)-2-amino-3- phenylpropanoyl- silybin as a promising inhibitor of IAV infection.
PMID:
23836164
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23836164