Identification of 5-methoxy-2-(diformylmethylidene)-3,3-dimethylindole as an anti-influenza a virus agent

Ming Cheang Tan, Wan Ying Wong, Wei Lun Ng, Kok Siong Yeo, Taznim Begam, Mohd Mohidin, Yat Yuen Lim, Fadhil Lafta, Hapipah Mohd Ali, Chee Kwee Ea

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Influenza virus is estimated to cause 3-5 million severe complications and about 250-500 thousand deaths per year. Different kinds of anti-influenza virus drugs have been developed. However, the emergence of drug resistant strains has presented a big challenge for efficient antiviral therapy. Indole derivatives have been shown to exhibit both antiviral and anti-inflammatory activities. In this study, we adopted a cell-based system to screen for potential anti-IAV agents. Four indole derivatives (named 525A, 526A, 527A and 528A) were subjected to the antiviral screening, of which 526A was selected for further investigation. We reported that pre-treating cells with 526A protects cells from IAV infection. Furthermore, 526A inhibits IAV replication by inhibiting the expression of IAV genes. Interestingly, 526A suppresses the activation of IRF3 and STAT1 in host cells and thus represses the production of type I interferon response and cytokines in IAV-infected cells. Importantly, 526A also partially blocks the activation of RIG-I pathway. Taken together, these results suggest that 526A may be a potential anti-influenza A virus agent.

Original languageEnglish (US)
Article numbere0170352
JournalPLoS One
Volume12
Issue number1
DOIs
StatePublished - Jan 1 2017

Fingerprint

Orthomyxoviridae
Viruses
Antiviral Agents
Chemical activation
Derivatives
indoles
Interferon Type I
cells
Pharmaceutical Preparations
Screening
Anti-Inflammatory Agents
Genes
drugs
Cytokines
Influenza A virus
interferons
anti-inflammatory activity
cytokines
death
screening

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Identification of 5-methoxy-2-(diformylmethylidene)-3,3-dimethylindole as an anti-influenza a virus agent. / Tan, Ming Cheang; Wong, Wan Ying; Ng, Wei Lun; Yeo, Kok Siong; Begam, Taznim; Mohidin, Mohd; Lim, Yat Yuen; Lafta, Fadhil; Ali, Hapipah Mohd; Ea, Chee Kwee.

In: PLoS One, Vol. 12, No. 1, e0170352, 01.01.2017.

Research output: Contribution to journalArticle

Tan, MC, Wong, WY, Ng, WL, Yeo, KS, Begam, T, Mohidin, M, Lim, YY, Lafta, F, Ali, HM & Ea, CK 2017, 'Identification of 5-methoxy-2-(diformylmethylidene)-3,3-dimethylindole as an anti-influenza a virus agent', PLoS One, vol. 12, no. 1, e0170352. https://doi.org/10.1371/journal.pone.0170352
Tan, Ming Cheang ; Wong, Wan Ying ; Ng, Wei Lun ; Yeo, Kok Siong ; Begam, Taznim ; Mohidin, Mohd ; Lim, Yat Yuen ; Lafta, Fadhil ; Ali, Hapipah Mohd ; Ea, Chee Kwee. / Identification of 5-methoxy-2-(diformylmethylidene)-3,3-dimethylindole as an anti-influenza a virus agent. In: PLoS One. 2017 ; Vol. 12, No. 1.
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