<i>Bruguiera gymnorhiza</i> (L.) Lam. at the Forefront of Pharma to Confront Zika Virus and Microbial Infections—An In Vitro and In Silico Perspective

The recent emergence of Zika virus (ZIKV) in Brazil and the increasing resistance developed by pathogenic bacteria to nearly all existing antibiotics should be taken as a wakeup call for the international authority as this represents a risk for global public health. The lack of antiviral drugs and e...

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Main Authors: Nabeelah Bibi Sadeer, Juliano G. Haddad, Mohammed Oday Ezzat, Philippe Desprès, Hassan H. Abdallah, Gokhan Zengin, Ahmet Uysal, Chaker El Kalamouni, Monica Gallo, Domenico Montesano, Mohamad Fawzi Mahomoodally
Format: Article
Language:English
Published: MDPI AG 2021-09-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/26/19/5768
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author Nabeelah Bibi Sadeer
Juliano G. Haddad
Mohammed Oday Ezzat
Philippe Desprès
Hassan H. Abdallah
Gokhan Zengin
Ahmet Uysal
Chaker El Kalamouni
Monica Gallo
Domenico Montesano
Mohamad Fawzi Mahomoodally
author_facet Nabeelah Bibi Sadeer
Juliano G. Haddad
Mohammed Oday Ezzat
Philippe Desprès
Hassan H. Abdallah
Gokhan Zengin
Ahmet Uysal
Chaker El Kalamouni
Monica Gallo
Domenico Montesano
Mohamad Fawzi Mahomoodally
author_sort Nabeelah Bibi Sadeer
collection DOAJ
description The recent emergence of Zika virus (ZIKV) in Brazil and the increasing resistance developed by pathogenic bacteria to nearly all existing antibiotics should be taken as a wakeup call for the international authority as this represents a risk for global public health. The lack of antiviral drugs and effective antibiotics on the market triggers the need to search for safe therapeutics from medicinal plants to fight viral and microbial infections. In the present study, we investigated whether a mangrove plant, <i>Bruguiera gymnorhiza</i> (L.) Lam. (<i>B. gymnorhiza</i>) collected in Mauritius, possesses antimicrobial and antibiotic potentiating abilities and exerts anti-ZIKV activity at non-cytotoxic doses. Microorganisms <i>Escherichia coli</i> ATCC 25922, <i>Pseudomonas aeruginosa</i> ATCC 27853, <i>Klebsiella pneumoniae</i> ATCC 70603, methicillin-resistant <i>Staphylococcus aureus</i> ATCC 43300 (MRSA), <i>Salmonella enteritidis</i> ATCC 13076, <i>Sarcina lutea</i> ATCC 9341, <i>Proteus mirabilis</i> ATCC 25933, <i>Bacillus cereus</i> ATCC 11778 and <i>Candida albicans</i> ATCC 26555 were used to evaluate the antimicrobial properties. Ciprofloxacin, chloramphenicol and streptomycin antibiotics were used for assessing antibiotic potentiating activity. ZIKV<sup>MC-MR766NIID</sup> (ZIKV<sup>GFP</sup>) was used for assessing anti-ZIKV activity. In silico docking (Autodock 4) and ADME (SwissADME) analyses were performed on collected data. Antimicrobial results revealed that <i>Bruguiera</i> twig ethyl acetate (BTE) was the most potent extract inhibiting the growth of all nine microbes tested, with minimum inhibitory concentrations ranging from 0.19–0.39 mg/mL. BTE showed partial synergy effects against MRSA and <i>Pseudomonas aeruginosa</i> when applied in combination with streptomycin and ciprofloxacin, respectively. By using a recombinant ZIKV-expressing reporter GFP protein, we identified both <i>Bruguiera</i> root aqueous and <i>Bruguiera</i> fruit aqueous extracts as potent inhibitors of ZIKV infection in human epithelial A549 cells. The mechanisms by which such extracts prevented ZIKV infection are linked to the inability of the virus to bind to the host cell surface. In silico docking showed that ZIKV E protein, which is involved in cell receptor binding, could be a target for cryptochlorogenic acid, a chemical compound identified in <i>B. gymnorhiza</i>. From ADME results, cryptochlorogenic acid is predicted to be not orally bioavailable because it is too polar. Scientific data collected in this present work can open a new avenue for the development of potential inhibitors from <i>B. gymnorhiza</i> to fight ZIKV and microbial infections in the future.
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spelling doaj.art-010e761138f4446d92a81239e39f5c132023-11-22T16:32:23ZengMDPI AGMolecules1420-30492021-09-012619576810.3390/molecules26195768<i>Bruguiera gymnorhiza</i> (L.) Lam. at the Forefront of Pharma to Confront Zika Virus and Microbial Infections—An In Vitro and In Silico PerspectiveNabeelah Bibi Sadeer0Juliano G. Haddad1Mohammed Oday Ezzat2Philippe Desprès3Hassan H. Abdallah4Gokhan Zengin5Ahmet Uysal6Chaker El Kalamouni7Monica Gallo8Domenico Montesano9Mohamad Fawzi Mahomoodally10Department of Health Sciences, Faculty of Medicine and Health Sciences, University of Mauritius, Réduit 80837, MauritiusUnité Mixte Processus Infectieux en Milieu Insulaire Tropical, Plateforme Technologique CYROI, Université de la Réunion, INSERM U1187, CNRS UMR 9192, IRD UMR 249, 94791 Sainte Clotilde, La Réunion, FranceDepartment of Chemistry, College of Education for Women, University of Anbar, Ramadi 31001, IraqUnité Mixte Processus Infectieux en Milieu Insulaire Tropical, Plateforme Technologique CYROI, Université de la Réunion, INSERM U1187, CNRS UMR 9192, IRD UMR 249, 94791 Sainte Clotilde, La Réunion, FranceChemistry Department, College of Education, Salahaddin University-Erbil, Erbil 44001, IraqDepartment of Biology, Science Faculty, Selcuk University, Campus, 42130 Konya, TurkeyDepartment of Medicinal Laboratory, Vocational School of Health Services, Selcuk University, 42130 Konya, TurkeyUnité Mixte Processus Infectieux en Milieu Insulaire Tropical, Plateforme Technologique CYROI, Université de la Réunion, INSERM U1187, CNRS UMR 9192, IRD UMR 249, 94791 Sainte Clotilde, La Réunion, FranceDepartment of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, via Pansini 5, 80131 Naples, ItalyDepartment of Pharmacy, University of Naples Federico II, via D. Montesano 49, 80131 Naples, ItalyDepartment of Health Sciences, Faculty of Medicine and Health Sciences, University of Mauritius, Réduit 80837, MauritiusThe recent emergence of Zika virus (ZIKV) in Brazil and the increasing resistance developed by pathogenic bacteria to nearly all existing antibiotics should be taken as a wakeup call for the international authority as this represents a risk for global public health. The lack of antiviral drugs and effective antibiotics on the market triggers the need to search for safe therapeutics from medicinal plants to fight viral and microbial infections. In the present study, we investigated whether a mangrove plant, <i>Bruguiera gymnorhiza</i> (L.) Lam. (<i>B. gymnorhiza</i>) collected in Mauritius, possesses antimicrobial and antibiotic potentiating abilities and exerts anti-ZIKV activity at non-cytotoxic doses. Microorganisms <i>Escherichia coli</i> ATCC 25922, <i>Pseudomonas aeruginosa</i> ATCC 27853, <i>Klebsiella pneumoniae</i> ATCC 70603, methicillin-resistant <i>Staphylococcus aureus</i> ATCC 43300 (MRSA), <i>Salmonella enteritidis</i> ATCC 13076, <i>Sarcina lutea</i> ATCC 9341, <i>Proteus mirabilis</i> ATCC 25933, <i>Bacillus cereus</i> ATCC 11778 and <i>Candida albicans</i> ATCC 26555 were used to evaluate the antimicrobial properties. Ciprofloxacin, chloramphenicol and streptomycin antibiotics were used for assessing antibiotic potentiating activity. ZIKV<sup>MC-MR766NIID</sup> (ZIKV<sup>GFP</sup>) was used for assessing anti-ZIKV activity. In silico docking (Autodock 4) and ADME (SwissADME) analyses were performed on collected data. Antimicrobial results revealed that <i>Bruguiera</i> twig ethyl acetate (BTE) was the most potent extract inhibiting the growth of all nine microbes tested, with minimum inhibitory concentrations ranging from 0.19–0.39 mg/mL. BTE showed partial synergy effects against MRSA and <i>Pseudomonas aeruginosa</i> when applied in combination with streptomycin and ciprofloxacin, respectively. By using a recombinant ZIKV-expressing reporter GFP protein, we identified both <i>Bruguiera</i> root aqueous and <i>Bruguiera</i> fruit aqueous extracts as potent inhibitors of ZIKV infection in human epithelial A549 cells. The mechanisms by which such extracts prevented ZIKV infection are linked to the inability of the virus to bind to the host cell surface. In silico docking showed that ZIKV E protein, which is involved in cell receptor binding, could be a target for cryptochlorogenic acid, a chemical compound identified in <i>B. gymnorhiza</i>. From ADME results, cryptochlorogenic acid is predicted to be not orally bioavailable because it is too polar. Scientific data collected in this present work can open a new avenue for the development of potential inhibitors from <i>B. gymnorhiza</i> to fight ZIKV and microbial infections in the future.https://www.mdpi.com/1420-3049/26/19/5768mangrove plantsantiviralantimicrobialenvelope proteinADMEpharmacokinetics
spellingShingle Nabeelah Bibi Sadeer
Juliano G. Haddad
Mohammed Oday Ezzat
Philippe Desprès
Hassan H. Abdallah
Gokhan Zengin
Ahmet Uysal
Chaker El Kalamouni
Monica Gallo
Domenico Montesano
Mohamad Fawzi Mahomoodally
<i>Bruguiera gymnorhiza</i> (L.) Lam. at the Forefront of Pharma to Confront Zika Virus and Microbial Infections—An In Vitro and In Silico Perspective
Molecules
mangrove plants
antiviral
antimicrobial
envelope protein
ADME
pharmacokinetics
title <i>Bruguiera gymnorhiza</i> (L.) Lam. at the Forefront of Pharma to Confront Zika Virus and Microbial Infections—An In Vitro and In Silico Perspective
title_full <i>Bruguiera gymnorhiza</i> (L.) Lam. at the Forefront of Pharma to Confront Zika Virus and Microbial Infections—An In Vitro and In Silico Perspective
title_fullStr <i>Bruguiera gymnorhiza</i> (L.) Lam. at the Forefront of Pharma to Confront Zika Virus and Microbial Infections—An In Vitro and In Silico Perspective
title_full_unstemmed <i>Bruguiera gymnorhiza</i> (L.) Lam. at the Forefront of Pharma to Confront Zika Virus and Microbial Infections—An In Vitro and In Silico Perspective
title_short <i>Bruguiera gymnorhiza</i> (L.) Lam. at the Forefront of Pharma to Confront Zika Virus and Microbial Infections—An In Vitro and In Silico Perspective
title_sort i bruguiera gymnorhiza i l lam at the forefront of pharma to confront zika virus and microbial infections an in vitro and in silico perspective
topic mangrove plants
antiviral
antimicrobial
envelope protein
ADME
pharmacokinetics
url https://www.mdpi.com/1420-3049/26/19/5768
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