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In vitro study of BromAc on SARS-CoV-2 spike and envelope protein shows synergy and disintegration at modest concentrations

Javed Akhter, Krishna Pillai, Samina Badar, View ORCID ProfileAhmed Mekkawy, View ORCID ProfileSarah J Valle, View ORCID ProfileDavid L. Morris
doi: https://doi.org/10.1101/2020.09.07.286906
Javed Akhter
1Department of Surgery, St George Hospital, Sydney NSW Australia
2Mucpharm Pty Ltd, Australia
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Krishna Pillai
2Mucpharm Pty Ltd, Australia
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Samina Badar
1Department of Surgery, St George Hospital, Sydney NSW Australia
3University of New South Wales, St George & Sutherland Clinical School, Sydney, NSW, Australia
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Ahmed Mekkawy
1Department of Surgery, St George Hospital, Sydney NSW Australia
2Mucpharm Pty Ltd, Australia
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  • ORCID record for Ahmed Mekkawy
Sarah J Valle
2Mucpharm Pty Ltd, Australia
3University of New South Wales, St George & Sutherland Clinical School, Sydney, NSW, Australia
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David L. Morris
1Department of Surgery, St George Hospital, Sydney NSW Australia
2Mucpharm Pty Ltd, Australia
3University of New South Wales, St George & Sutherland Clinical School, Sydney, NSW, Australia
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  • ORCID record for David L. Morris
  • For correspondence: david.morris@unsw.edu.au
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Abstract

Objectives SARS-CoV-2 infection is the cause of a worldwide pandemic, currently with limited therapeutic options. It is characterised by being highly contagious and nasal mucosa appears to be the primary site with subsequent spread to the lungs and elsewhere. BromAc (Bromelain & Acetylcysteine) has been described to disrupt glycoproteins by the synchronous breakage of glycosidic linkages and disulphide bonds. The spike protein of SARS-CoV-2 is an attractive target as it is essential for binding to the ACE2 receptor in host cells and is formed of glycoprotein and disulphide bridges for stabilisation. Hence, we sought to determine whether BromAc has activity on the spike and envelope protein specific to SARS-CoV-2 virus.

Design Gel electrophoresis analysis was carried out on recombinant spike and envelope proteins that were treated with a range of concentrations of single agents and BromAc. For UV analysis of disulfide bonds reduction, both spike and envelope protein were treated with Acetylcysteine with the determination of loss of disulfide bonds.

Results Recombinant spike and envelope SARS-CoV-2 protein were fragmented by BromAc whilst single agents had minimal effect. Spike and envelope proteins disulphide bonds were reduced by Acetylcysteine.

Conclusion BromAc disintegrates the spike and envelope protein from SARS-CoV-2 and may render it non-infective. In vitro tests on live virus have been encouraging and clinical testing through nasal administration in patients with early SARS-CoV-2 infection is imminent.

Competing Interest Statement

Disclosures & conflicts of interest Professor David Morris is the co-inventor and assignee of the Licence for this study and director of the spin-off sponsor company, Mucpharm Pty Ltd. Dr Javed Akhter, Dr Krishna Pillai and Dr Ahmed Mekkawy are employees of Mucpharm Pty Ltd. Miss Sarah Valle is partly employed by Mucpharm for its cancer development and is supported by an Australian Government Research Training Program Scholarship. Funding This research is partly funded by Mucpharm Pty Ltd, Australia.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted September 08, 2020.
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In vitro study of BromAc on SARS-CoV-2 spike and envelope protein shows synergy and disintegration at modest concentrations
Javed Akhter, Krishna Pillai, Samina Badar, Ahmed Mekkawy, Sarah J Valle, David L. Morris
bioRxiv 2020.09.07.286906; doi: https://doi.org/10.1101/2020.09.07.286906
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In vitro study of BromAc on SARS-CoV-2 spike and envelope protein shows synergy and disintegration at modest concentrations
Javed Akhter, Krishna Pillai, Samina Badar, Ahmed Mekkawy, Sarah J Valle, David L. Morris
bioRxiv 2020.09.07.286906; doi: https://doi.org/10.1101/2020.09.07.286906

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