TY - JOUR
T1 - Small molecule inhibits respiratory syncytial virus entry and infection by blocking the interaction of the viral fusion protein with the cell membrane
AU - Tang, Wei
AU - Li, Manmei
AU - Liu, Yujun
AU - Liang, Ning
AU - Yang, Zhu
AU - Zhao, Yanxiang
AU - Wu, Shuai
AU - Lu, Sangwei
AU - Li, Yaolan
AU - Liu, Fenyong
PY - 2019/3/1
Y1 - 2019/3/1
N2 - Antiviral drug development against respiratory syncytial virus (RSV) is urgently needed due to the public health significance of the viral infection. Here, we report the anti-RSV activity of a small molecule, (1S,3R,4R,5R)-3,4-bis{[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy}-l,5-dihydroxycyclohexane-1-ca methyl ester (3,4-DCQAME) or 3,4-O-Dicaffeoylquinic acid methyl ester, which can be isolated from several plants of traditional Chinese medicine. We showed for the first time that compound 3,4-DCQAME potently inhibits RSV entry and infection. In vitro, 3,4-DCQAME can interact with F(ecto), the ectodomain of RSV fusion (F) protein. In cultured cells, the compound can block the interaction of F(ecto) protein with the cellular membrane and inhibit viral fusion during RSV entry, leading to inhibition of viral gene expression and infection. In RSV-infected mice that were treated with 3,4-DCQAME, we observed a reduction of RSV-induced pathologic changes and substantial inhibition of viral infection and growth in the lung tissues. Our results provide the first direct evidence of the anti-RSV activity of 3,4-DCQAME. Furthermore, these results suggest that 3,4-DCQAME represents a promising lead compound for anti-RSV therapeutic development.—Tang, W., Li, M., Liu, Y., Liang, N., Yang, Z., Zhao, Y., Wu, S., Lu, S., Li, Y., Liu, F. Small molecule inhibits respiratory syncytial virus entry and infection by blocking the interaction of the viral fusion protein with the cell membrane. FASEB J. 33, 4287–4299 (2019). www.fasebj.org.
AB - Antiviral drug development against respiratory syncytial virus (RSV) is urgently needed due to the public health significance of the viral infection. Here, we report the anti-RSV activity of a small molecule, (1S,3R,4R,5R)-3,4-bis{[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy}-l,5-dihydroxycyclohexane-1-ca methyl ester (3,4-DCQAME) or 3,4-O-Dicaffeoylquinic acid methyl ester, which can be isolated from several plants of traditional Chinese medicine. We showed for the first time that compound 3,4-DCQAME potently inhibits RSV entry and infection. In vitro, 3,4-DCQAME can interact with F(ecto), the ectodomain of RSV fusion (F) protein. In cultured cells, the compound can block the interaction of F(ecto) protein with the cellular membrane and inhibit viral fusion during RSV entry, leading to inhibition of viral gene expression and infection. In RSV-infected mice that were treated with 3,4-DCQAME, we observed a reduction of RSV-induced pathologic changes and substantial inhibition of viral infection and growth in the lung tissues. Our results provide the first direct evidence of the anti-RSV activity of 3,4-DCQAME. Furthermore, these results suggest that 3,4-DCQAME represents a promising lead compound for anti-RSV therapeutic development.—Tang, W., Li, M., Liu, Y., Liang, N., Yang, Z., Zhao, Y., Wu, S., Lu, S., Li, Y., Liu, F. Small molecule inhibits respiratory syncytial virus entry and infection by blocking the interaction of the viral fusion protein with the cell membrane. FASEB J. 33, 4287–4299 (2019). www.fasebj.org.
KW - antiviral
KW - drug resistance
KW - mice
KW - RSV
KW - viral entry
UR - http://www.scopus.com/inward/record.url?scp=85078883495&partnerID=8YFLogxK
U2 - 10.1096/fj.201800579R
DO - 10.1096/fj.201800579R
M3 - Journal article
C2 - 30571312
AN - SCOPUS:85078883495
SN - 0892-6638
VL - 33
SP - 4287
EP - 4299
JO - FASEB Journal
JF - FASEB Journal
IS - 3
ER -