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In silico study of azithromycin, chloroquine and hydroxychloroquine and their potential mechanisms of action against SARS-CoV-2 infection.
Braz, Helyson Lucas Bezerra; Silveira, João Alison de Moraes; Marinho, Aline Diogo; de Moraes, Maria Elisabete Amaral; Moraes Filho, Manoel Odorico de; Monteiro, Helena Serra Azul; Jorge, Roberta Jeane Bezerra.
  • Braz HLB; 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
  • Silveira JAM; Drug Research and Development Center, Federal University of Ceara, Coronel Nunes de Melo St., 1000, 60.430-275, Fortaleza-CE, Brazil; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceara, Coronel Nunes de Melo St., 1127, 60.430-275, Fortaleza-CE, Brazil.
  • Marinho AD; Drug Research and Development Center, Federal University of Ceara, Coronel Nunes de Melo St., 1000, 60.430-275, Fortaleza-CE, Brazil; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceara, Coronel Nunes de Melo St., 1127, 60.430-275, Fortaleza-CE, Brazil.
  • de Moraes MEA; Drug Research and Development Center, Federal University of Ceara, Coronel Nunes de Melo St., 1000, 60.430-275, Fortaleza-CE, Brazil; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceara, Coronel Nunes de Melo St., 1127, 60.430-275, Fortaleza-CE, Brazil.
  • Moraes Filho MO; Drug Research and Development Center, Federal University of Ceara, Coronel Nunes de Melo St., 1000, 60.430-275, Fortaleza-CE, Brazil; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceara, Coronel Nunes de Melo St., 1127, 60.430-275, Fortaleza-CE, Brazil.
  • Monteiro HSA; Drug Research and Development Center, Federal University of Ceara, Coronel Nunes de Melo St., 1000, 60.430-275, Fortaleza-CE, Brazil; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceara, Coronel Nunes de Melo St., 1127, 60.430-275, Fortaleza-CE, Brazil.
  • Jorge RJB; Drug Research and Development Center, Federal University of Ceara, Coronel Nunes de Melo St., 1000, 60.430-275, Fortaleza-CE, Brazil; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceara, Coronel Nunes de Melo St., 1127, 60.430-275, Fortaleza-CE, Brazil. Electro
Int J Antimicrob Agents ; 56(3): 106119, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-690298
ABSTRACT
Coronavirus 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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Cysteine Endopeptidases / Chloroquine / Viral Nonstructural Proteins / Azithromycin / Peptidyl-Dipeptidase A / Cathepsin L / Spike Glycoprotein, Coronavirus / Betacoronavirus / Hydroxychloroquine Type of study: Prognostic study Language: English Journal: Int J Antimicrob Agents Year: 2020 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Cysteine Endopeptidases / Chloroquine / Viral Nonstructural Proteins / Azithromycin / Peptidyl-Dipeptidase A / Cathepsin L / Spike Glycoprotein, Coronavirus / Betacoronavirus / Hydroxychloroquine Type of study: Prognostic study Language: English Journal: Int J Antimicrob Agents Year: 2020 Document Type: Article