• Helyson Lucas Bezerra Braz, João Alison de Moraes Silveira, Aline Diogo Marinho, Maria Elisabete Amaral de Moraes, Manoel Odorico de Moraes Filho, Helena Serra Azul Monteiro, and Roberta Jeane Bezerra Jorge.
• Postgraduate Program in Morphological Science, Department of Morphology, School of Medicine, Federal University of Ceara, Delmiro de Farias St., 60.430-170, Fortaleza-CE, Brazil; Drug Research and Development Center, Federal University of Ceara, Coronel Nunes de Melo St., 1000, 60.430-275, Fortaleza-CE, Brazil.
• Int. J. Antimicrob. Agents. 2020 Sep 1; 56 (3): 106119.

AbstractCoronavirus disease 2019 (COVID-19) is a highly transmissible viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clinical trials have reported improved outcomes resulting from an effective reduction or absence of viral load when patients were treated with chloroquine (CQ) or hydroxychloroquine (HCQ). In addition, the effects of these drugs were improved by simultaneous administration of azithromycin (AZM). The receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein binds to the cell surface angiotensin-converting enzyme 2 (ACE2) receptor, allowing virus entry and replication in host cells. The viral main protease (Mpro) and host cathepsin L (CTSL) are among the proteolytic systems involved in SARS-CoV-2 S protein activation. Hence, molecular docking studies were performed to test the binding performance of these three drugs against four targets. The findings showed AZM affinity scores (ΔG) with strong interactions with ACE2, CTSL, Mpro and RBD. CQ affinity scores showed three low-energy results (less negative) with ACE2, CTSL and RBD, and a firm bond score with Mpro. For HCQ, two results (ACE2 and Mpro) were firmly bound to the receptors, however CTSL and RBD showed low interaction energies. The differences in better interactions and affinity between HCQ and CQ with ACE2 and Mpro were probably due to structural differences between the drugs. On other hand, AZM not only showed more negative (better) values in affinity, but also in the number of interactions in all targets. Nevertheless, further studies are needed to investigate the antiviral properties of these drugs against SARS-CoV-2.Copyright © 2020 Elsevier Ltd. All rights reserved.

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