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Innovative Medicines & Omics

ORIGINAL RESEARCH ARTICLE
Potent and selective inhibitory effect of

4-aminoquinoline derivatives on SARS-CoV-2
replication

Nícolas Glanzmann 1† , Thamara Kelcya F. Oliveira 2,3† , Vinicius Carius de Souza 4† ,
Amanda R. Tucci 2,3 , Eduarda Alves Penna , Alice Santos Rosa 2,3 ,
4
Maria Luiza Pereira Baltazar , Matheus José Novais Landim ,
4
4
Vivian Neuza S. Ferreira 2 , Pamella Constantino-Teles 2,3 ,
Daniel Dias Coutinho Souza 2,3 , Sylvia Roxo 2 , Caroline Souza de Freitas 5,6 ,
Aline de Paula Dias da Silva 5,6 , Thiago Moreno Lopes Souza 5,6 ,
4†
Priscila Vanessa S. Zabala Capriles * , Milene Dias Miranda 2,3† * , and
1†
Adilson D. da Silva *
1 Department of Chemistry, Federal University of Juiz de Fora, Juiz de Fora, Minas Gerais, Brazil
2 Viral Morphology and Morphogenesis Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz
Foundation, Rio de Janeiro, Brazil
3 Postgraduate Program in Cellular and Molecular Biology, Oswaldo Cruz Institute, Oswaldo Cruz
Foundation, Rio de Janeiro, Brazil
4 Department of Computer Science, Institute of Exact Sciences, Federal University of Juiz de Fora,
Juiz de Fora, Minas Gerais, Brazil

† These authors contributed equally
to this work. Abstract
*Corresponding authors:
Adilson D. da Silva The global coronavirus disease 2019 (COVID-19) pandemic, caused by the highly
(david.silva@ufjf.br) infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had
Milene Dias Miranda resulted in significant mortality worldwide. In 2020, the World Health Organization
(mmiranda@ioc.fiocruz.br)
Priscila Vanessa S. Zabala Capriles started the solidarity clinical trial to assess the efficacy of four proposed therapeutic
(capriles@ice.ufjf.br) strategies, including chloroquine (CQ), a 4-aminoquinoline molecule. However, CQ
Citation: Glanzmann N, lacks clinical benefit and, therefore, failed to show in vitro anti-SARS-CoV-2 activity in
Oliveira TKF, de Souza VC, et al. TMPRSS2-expressing cells, such as Calu-3 cell line, which recapitulate human type II
Potent and selective inhibitory effect pneumocytes. Nevertheless, other 4-aminoquinoline derivatives have shown high
of 4-aminoquinoline derivatives on pro
SARS-CoV-2 replication. Innov Med affinity toward the SARS-CoV-2 main protease (M ). This study aimed to evaluate,
Omics. 2024;1(1):88-106. in vitro and in silico, the inhibitory potential of nine 4-aminoquinoline derivatives
doi: 10.36922/imo.3442 against SARS-CoV-2, building upon the observed antiviral activity of established
Received: April 17, 2024 antimalarial drugs. We assessed the ability of these derivatives to inhibit SARS-
Accepted: May 23, 2024 CoV-2 (wild type and Omicron variant) replication in Vero E6 and Calu-3 cell lines.
Published Online: June 21, 2024
In addition, we conducted docking studies to determine the binding affinity and
Copyright: © 2024 Author(s). protein-ligand interactions. Notably, these derivatives exhibited potent antiviral
This is an Open-Access article activity with low cytotoxicity in Vero E6 and Calu-3 cell models. In silico investigations
distributed under the terms of the
pro
Creative Commons Attribution targeting the M enzyme supported the potential of the derivatives as promising
License, permitting distribution, agents in the fight against SARS-CoV-2. Our findings underscore the potential of
and reproduction in any medium, these 4-aminoquinoline derivatives as robust inhibitors of SARS-CoV-2 and advocate
provided the original work is
properly cited. for further research to explore their therapeutic applications, providing valuable
insights for future drug development strategies.
Publisher’s Note: AccScience
Publishing remains neutral with
regard to jurisdictional claims in
published maps and institutional Keywords: SARS-CoV-2; 4-aminoquinolines; Vero E6; Calu-3; Molecular docking
affiliations.

Volume 1 Issue 1 (2024) 88 doi: 10.36922/imo.3442