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.

Indole – a promising pharmacophore in recent antiviral drug discovery

“…87,88 A set of novel indole derivatives are prepared and evaluated for anti-influenza properties. 89 The four new synthetic indole derivatives 96-99 (Fig. 32) are checked for cytotoxicity wherein the derivatives are found to be non-toxic (IC 50 = 266-442 μM).…”

Melatonin and other indoles show antiviral activities against swine coronaviruses in vitro at pharmacological concentrations

“…Indole is an aromatic heterocyclic organic compound with a bicyclic structure, which consists of pyrrole and benzene in parallel. 19 Generally speaking, heterocyclic compounds are important structures of pharmacologically active compounds. Indole stents have been widely used in the design of antiviral drugs.…”

A conceptual review of rhodanine: current applications of antiviral drugs, anticancer and antimicrobial activities

“…One of the main factors of the neurotransmitter serotonin and an indole derivative is amino acid tryptophan. So far, indoles have illustrated significant pharmacological functions and potent physiological activities like anti-HIV activity [48,49], antiinflammatory and antioxidant [50], antiviral [51][52][53], antineoplastic [51,54,55] and antimicrobial [56,57]. Another derivative of indole is N-Arylsulfonylindoles, which can widely use for chemical drug studies and also act as anti-AIDS drugs [58], antifungal agents [59] 5-HT6 receptor antagonists [60].…”