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
Affiliations
- Belén Martinez-Gualda
- KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Rega Institute for Medical Research, Laboratory of Medicinal Chemistry, Leuven, Belgium
- Belén Martinez-Gualda
- KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium
- Mirthe Graus
- KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium
- Anita Camps
- KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium
- Emiel Vanhulle
- KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium
- Sirle Saul
- Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA, United States
- Sirle Saul
- Department of Microbiology and Immunology, Stanford University, Stanford, CA, United States
- Siavash Azari
- Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA, United States
- Siavash Azari
- Department of Microbiology and Immunology, Stanford University, Stanford, CA, United States
- Do Hoang Nhu Tran
- Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA, United States
- Do Hoang Nhu Tran
- Department of Microbiology and Immunology, Stanford University, Stanford, CA, United States
- Laura Vangeel
- KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium
- Winston Chiu
- KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium
- Johan Neyts
- KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium
- Dominique Schols
- KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium
- Shirit Einav
- Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA, United States
- Shirit Einav
- Department of Microbiology and Immunology, Stanford University, Stanford, CA, United States
- Shirit Einav
- Chan Zuckerberg Biohub, San Francisco, CA, United States
- Kurt Vermeire
- KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium
- Steven De Jonghe
- KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium
- DOI
- https://doi.org/10.3389/fchem.2022.1058229
- Journal volume & issue
-
Vol. 10
Abstract
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
- 7-aza-indole
- pyrrolo[2,3-b]pyridine
- respiratory syncytial virus (RSV)
- severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
- Venezuelan equine encephalitis virus (VEEV)
- adaptor-associated kinase 1
