The azaindole (AI) framework continues to play a significant role in the design of new
antiviral agents. Modulating the position and isosteric replacement of the nitrogen atom
of AI analogs notably influences the intrinsic physicochemical properties of lead
compounds. The intra- and intermolecular interactions of AI derivatives with host
receptors or viral proteins can also be fine tuned by carefully placing the nitrogen
atom in the heterocyclic core. This wide-ranging perspective article focuses on AIs that
have considerable utility in drug discovery programs against RNA viruses. The inhibition
of influenza A, human immunodeficiency, respiratory syncytial, neurotropic alpha,
dengue, ebola, and hepatitis C viruses by AI analogs is extensively reviewed to assess
their plausible future potential in antiviral drug discovery. The binding interaction of
AIs with the target protein is examined to derive a structural basis for designing new
antiviral agents.