title: Identification of 5-Methoxy-2-(Diformylmethylidene)-3,3-Dimethylindole as an Anti-Influenza A Virus Agent.
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.
authors.affiliation: Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Ming Cheang
authors.initials: MC
authors.lastname: Tan
authors.affiliation: Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Wan Ying
authors.initials: WY
authors.lastname: Wong
authors.affiliation: Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Wei Lun
authors.initials: WL
authors.lastname: Ng
authors.affiliation: Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Kok Siong
authors.initials: KS
authors.lastname: Yeo
authors.affiliation: Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Taznim Begam Mohd
authors.initials: TB
authors.lastname: Mohidin
authors.affiliation: Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Yat-Yuen
authors.initials: YY
authors.lastname: Lim
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Fadhil
authors.initials: F
authors.lastname: Lafta
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Hapipah
authors.initials: H
authors.lastname: Mohd Ali
authors.affiliation: Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Chee-Kwee
authors.initials: CK
authors.lastname: Ea
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D009980:Influenza A virus / Q000187:drug effects* / Q000502:physiology; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D008315:Malondialdehyde / Q000031:analogs & derivatives* / Q000494:pharmacology; D050794:STAT1 Transcription Factor / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
chemical_list: C000621946:5-methoxy-2-(diformylmethylidene)-3,3-dimethylindole; D000998:Antiviral Agents; D007211:Indoles; D050838:Interferon Regulatory Factor-3; D050794:STAT1 Transcription Factor; D008315:Malondialdehyde