Work

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

Year: 2022

Type: article

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.

Source: Frontiers in Chemistry

DOI: 10.3389/fchem.2022.1058229

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

Institutions: Rega Institute for Medical Research, KU Leuven, Stanford Medicine, Stanford University, Chan Zuckerberg Biohub San Francisco

Language: English

Topic: Synthesis and biological activity

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,950

Funders: U.S. Department of Defense, Fonds Wetenschappelijk Onderzoek, KU Leuven, Vlaamse regering, Rega Foundation, Defense Threat Reduction Agency, National Institute of Allergy and Infectious Diseases, Hercule Programmes, Congressionally Directed Medical Research Programs

Awards: G21146293, G4119534169, NAK Inhibitors for Combating Dengue, Ebola, COVID-19, and Other Emerging Viral Infections, G5033194471, G5069427589, Selective AAK1 and GAK Inhibitors for Combating Dengue and Other Emerging Viral Infections, NAK INHIBITORS FOR COMBATING DENGUE, EBOLA, COVID-19, AND OTHER EMERGING VIRAL INFECTIONS, SELECTIVE AAK1 AND GAK INHIBITORS FOR COMBATING DENGUE AND OTHER EMERGING VIRAL INFECTIONS, Advancing the development of a novel class of small molecules for treating pan-coronavirus infections

OpenAlex ID: W4307556089

FWCI: 0.476

Cites: 33

Cited by: 10

Related to: 10