Small molecule inhibits respiratory syncytial virus entry and infection by blocking the interaction of the viral fusion protein with the cell membrane

Wei Tang, Manmei Li, Yujun Liu, Ning Liang, Zhu Yang, Yanxiang Zhao, Shuai Wu, Sangwei Lu, Yaolan Li, Fenyong Liu

Research output: Journal article publicationJournal articleAcademic researchpeer-review

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4287-4299
Number of pages13
JournalFASEB Journal
Volume33
Issue number3
DOIs
Publication statusPublished - 1 Mar 2019

Keywords

  • antiviral
  • drug resistance
  • mice
  • RSV
  • viral entry

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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