The Combination of Bromelain and Acetylcysteine (BromAc) Synergistically Inactivates SARS-CoV-2

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is the cause of a worldwide pandemic, currently with limited therapeutic options. The spike glycoprotein and envelope protein of SARS-CoV-2, containing disulfide bridges for stabilization, represent an attractive target as they are...

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Main Authors: Javed Akhter, Grégory Quéromès, Krishna Pillai, Vahan Kepenekian, Samina Badar, Ahmed H. Mekkawy, Emilie Frobert, Sarah J. Valle, David L. Morris
Format: Article
Language:English
Published: MDPI AG 2021-03-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/13/3/425
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author Javed Akhter
Grégory Quéromès
Krishna Pillai
Vahan Kepenekian
Samina Badar
Ahmed H. Mekkawy
Emilie Frobert
Sarah J. Valle
David L. Morris
author_facet Javed Akhter
Grégory Quéromès
Krishna Pillai
Vahan Kepenekian
Samina Badar
Ahmed H. Mekkawy
Emilie Frobert
Sarah J. Valle
David L. Morris
author_sort Javed Akhter
collection DOAJ
description Severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is the cause of a worldwide pandemic, currently with limited therapeutic options. The spike glycoprotein and envelope protein of SARS-CoV-2, containing disulfide bridges for stabilization, represent an attractive target as they are essential for binding to the ACE2 receptor in host cells present in the nasal mucosa. Bromelain and Acetylcysteine (BromAc) has synergistic action against glycoproteins by breakage of glycosidic linkages and disulfide bonds. We sought to determine the effect of BromAc on the spike and envelope proteins and its potential to reduce infectivity in host cells. Recombinant spike and envelope SARS-CoV-2 proteins were disrupted by BromAc. Spike and envelope protein disulfide bonds were reduced by Acetylcysteine. In in vitro whole virus culture of both wild-type and spike mutants, SARS-CoV-2 demonstrated a concentration-dependent inactivation from BromAc treatment but not from single agents. Clinical testing through nasal administration in patients with early SARS-CoV-2 infection is imminent.
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spelling doaj.art-8f4999e3b9c84264aae68a2a287167ca2023-12-03T12:52:21ZengMDPI AGViruses1999-49152021-03-0113342510.3390/v13030425The Combination of Bromelain and Acetylcysteine (BromAc) Synergistically Inactivates SARS-CoV-2Javed Akhter0Grégory Quéromès1Krishna Pillai2Vahan Kepenekian3Samina Badar4Ahmed H. Mekkawy5Emilie Frobert6Sarah J. Valle7David L. Morris8Department of Surgery, St. George Hospital, Sydney, NSW 2217, AustraliaCIRI, Centre International de Recherche en Infectiologie, Team VirPatH, Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007 Lyon, FranceMucpharm Pty Ltd., Sydney, NSW 2217, AustraliaDepartment of Surgery, St. George Hospital, Sydney, NSW 2217, AustraliaDepartment of Surgery, St. George Hospital, Sydney, NSW 2217, AustraliaDepartment of Surgery, St. George Hospital, Sydney, NSW 2217, AustraliaCIRI, Centre International de Recherche en Infectiologie, Team VirPatH, Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007 Lyon, FranceDepartment of Surgery, St. George Hospital, Sydney, NSW 2217, AustraliaDepartment of Surgery, St. George Hospital, Sydney, NSW 2217, AustraliaSevere acute respiratory syndrome coronavirus (SARS-CoV-2) infection is the cause of a worldwide pandemic, currently with limited therapeutic options. The spike glycoprotein and envelope protein of SARS-CoV-2, containing disulfide bridges for stabilization, represent an attractive target as they are essential for binding to the ACE2 receptor in host cells present in the nasal mucosa. Bromelain and Acetylcysteine (BromAc) has synergistic action against glycoproteins by breakage of glycosidic linkages and disulfide bonds. We sought to determine the effect of BromAc on the spike and envelope proteins and its potential to reduce infectivity in host cells. Recombinant spike and envelope SARS-CoV-2 proteins were disrupted by BromAc. Spike and envelope protein disulfide bonds were reduced by Acetylcysteine. In in vitro whole virus culture of both wild-type and spike mutants, SARS-CoV-2 demonstrated a concentration-dependent inactivation from BromAc treatment but not from single agents. Clinical testing through nasal administration in patients with early SARS-CoV-2 infection is imminent.https://www.mdpi.com/1999-4915/13/3/425SARS-CoV-2BromelainAcetylcysteineBromAcdrug repurposing
spellingShingle Javed Akhter
Grégory Quéromès
Krishna Pillai
Vahan Kepenekian
Samina Badar
Ahmed H. Mekkawy
Emilie Frobert
Sarah J. Valle
David L. Morris
The Combination of Bromelain and Acetylcysteine (BromAc) Synergistically Inactivates SARS-CoV-2
Viruses
SARS-CoV-2
Bromelain
Acetylcysteine
BromAc
drug repurposing
title The Combination of Bromelain and Acetylcysteine (BromAc) Synergistically Inactivates SARS-CoV-2
title_full The Combination of Bromelain and Acetylcysteine (BromAc) Synergistically Inactivates SARS-CoV-2
title_fullStr The Combination of Bromelain and Acetylcysteine (BromAc) Synergistically Inactivates SARS-CoV-2
title_full_unstemmed The Combination of Bromelain and Acetylcysteine (BromAc) Synergistically Inactivates SARS-CoV-2
title_short The Combination of Bromelain and Acetylcysteine (BromAc) Synergistically Inactivates SARS-CoV-2
title_sort combination of bromelain and acetylcysteine bromac synergistically inactivates sars cov 2
topic SARS-CoV-2
Bromelain
Acetylcysteine
BromAc
drug repurposing
url https://www.mdpi.com/1999-4915/13/3/425
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