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In silico study of azithromycin, chloroquine and hydroxychloroquine and their potential mechanisms of action against SARS-CoV-2 infection.
Int J Antimicrob Agents. 2020 Sep; 56(3):106119.IJ

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.

Authors+Show Affiliations

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.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.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.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.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.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.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. Electronic address: robertajeane@ufc.br.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32738306

Citation

Braz, Helyson Lucas Bezerra, et al. "In Silico Study of Azithromycin, Chloroquine and Hydroxychloroquine and Their Potential Mechanisms of Action Against SARS-CoV-2 Infection." International Journal of Antimicrobial Agents, vol. 56, no. 3, 2020, p. 106119.
Braz HLB, Silveira JAM, Marinho AD, et al. In silico study of azithromycin, chloroquine and hydroxychloroquine and their potential mechanisms of action against SARS-CoV-2 infection. Int J Antimicrob Agents. 2020;56(3):106119.
Braz, H. L. B., Silveira, J. A. M., Marinho, A. D., de Moraes, M. E. A., Moraes Filho, M. O., Monteiro, H. S. A., & Jorge, R. J. B. (2020). In silico study of azithromycin, chloroquine and hydroxychloroquine and their potential mechanisms of action against SARS-CoV-2 infection. International Journal of Antimicrobial Agents, 56(3), 106119. https://doi.org/10.1016/j.ijantimicag.2020.106119
Braz HLB, et al. In Silico Study of Azithromycin, Chloroquine and Hydroxychloroquine and Their Potential Mechanisms of Action Against SARS-CoV-2 Infection. Int J Antimicrob Agents. 2020;56(3):106119. PubMed PMID: 32738306.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In silico study of azithromycin, chloroquine and hydroxychloroquine and their potential mechanisms of action against SARS-CoV-2 infection. AU - Braz,Helyson Lucas Bezerra, AU - Silveira,João Alison de Moraes, AU - Marinho,Aline Diogo, AU - de Moraes,Maria Elisabete Amaral, AU - Moraes Filho,Manoel Odorico de, AU - Monteiro,Helena Serra Azul, AU - Jorge,Roberta Jeane Bezerra, Y1 - 2020/07/30/ PY - 2020/04/12/received PY - 2020/07/20/revised PY - 2020/07/23/accepted PY - 2020/8/2/pubmed PY - 2020/9/12/medline PY - 2020/8/2/entrez KW - Azithromycin KW - COVID-19 KW - Chloroquine KW - Coronavirus KW - Hydroxychloroquine KW - Molecular docking SP - 106119 EP - 106119 JF - International journal of antimicrobial agents JO - Int J Antimicrob Agents VL - 56 IS - 3 N2 - 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. SN - 1872-7913 UR - https://www.unboundmedicine.com/medline/citation/32738306/In_silico_study_of_azithromycin_chloroquine_and_hydroxychloroquine_and_their_potential_mechanisms_of_action_against_SARS_CoV_2_infection_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0924-8579(20)30302-2 DB - PRIME DP - Unbound Medicine ER -