Frontiers in Chemistry (Oct 2022)

Synthesis and evaluation of 3-alkynyl-5-aryl-7-aza-indoles as broad-spectrum antiviral agents

  • Belén Martinez-Gualda,
  • Belén Martinez-Gualda,
  • Mirthe Graus,
  • Anita Camps,
  • Emiel Vanhulle,
  • Sirle Saul,
  • Sirle Saul,
  • Siavash Azari,
  • Siavash Azari,
  • Do Hoang Nhu Tran,
  • Do Hoang Nhu Tran,
  • Laura Vangeel,
  • Winston Chiu,
  • Johan Neyts,
  • Dominique Schols,
  • Shirit Einav,
  • Shirit Einav,
  • Shirit Einav,
  • Kurt Vermeire,
  • Steven De Jonghe

DOI
https://doi.org/10.3389/fchem.2022.1058229
Journal volume & issue
Vol. 10

Abstract

Read online

RNA viral infections, including those caused by respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and Venezuelan Equine encephalitis virus (VEEV), pose a major global health challenge. Here, we report the synthesis and screening of a series of pyrrolo[2,3-b]pyridines targeting RSV, SARS-CoV-2 and/or VEEV. From this campaign, a series of lead compounds was generated that demonstrated antiviral activity in the low single-digit micromolar range against the various viruses and did not show cytotoxicity. These findings highlight the potential of 3-alkynyl-5-aryl-7-aza-indoles as a promising chemotype for the development of broad-spectrum antiviral agents.

Keywords