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SARS-CoV-2 inhibition in human airway epithelial cells using a mucoadhesive, amphiphilic chitosan that may serve as an anti-viral nasal spray

View ORCID ProfileKrzysztof Pyrć, View ORCID ProfileAleksandra Milewska, View ORCID ProfileEmilia Barreto Duran, Paweł Botwina, Rui Lopes, Alejandro Arenas-Pinto, Moutaz Badr, Ryan Mellor, Tammy L. Kalber, View ORCID ProfileDelmiro Fernandes-Reyes, Andreas G. Schätzlein, View ORCID ProfileIjeoma F. Uchegbu
doi: https://doi.org/10.1101/2020.12.10.413609
Krzysztof Pyrć
1Laboratory of Virology and ABSL3 Animal Facility at the Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7a, 30-387 Krakow, Poland
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Aleksandra Milewska
1Laboratory of Virology and ABSL3 Animal Facility at the Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7a, 30-387 Krakow, Poland
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Emilia Barreto Duran
1Laboratory of Virology and ABSL3 Animal Facility at the Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7a, 30-387 Krakow, Poland
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Paweł Botwina
1Laboratory of Virology and ABSL3 Animal Facility at the Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7a, 30-387 Krakow, Poland
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Rui Lopes
2Nanomerics Ltd., 6th Floor, 2 London Wall Place, London EC2Y 5AU United Kingdom
3UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX
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Alejandro Arenas-Pinto
4Centre for Clinical Research in Infection and Sexual Health, UCL Institute for Global Health, Mortimer Market Centre, off Capper Street, London WC1E 6JB
5MRC-Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, 90 High Holborn, London WC1V 6LJ
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Moutaz Badr
2Nanomerics Ltd., 6th Floor, 2 London Wall Place, London EC2Y 5AU United Kingdom
3UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX
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Ryan Mellor
2Nanomerics Ltd., 6th Floor, 2 London Wall Place, London EC2Y 5AU United Kingdom
3UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX
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Tammy L. Kalber
6Centre for Advanced Biomedical Imaging (CABI), Division of Medicine, University College London, London WC1E 6DD
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Delmiro Fernandes-Reyes
7Computer Science Department, University College London, Gower Street, London WC1E 6BT
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Andreas G. Schätzlein
2Nanomerics Ltd., 6th Floor, 2 London Wall Place, London EC2Y 5AU United Kingdom
3UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX
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Ijeoma F. Uchegbu
2Nanomerics Ltd., 6th Floor, 2 London Wall Place, London EC2Y 5AU United Kingdom
3UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX
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  • ORCID record for Ijeoma F. Uchegbu
  • For correspondence: ijeoma.uchegbu@ucl.ac.uk
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Abstract

There are currently no cures for coronavirus infections, making the prevention of infections the only course open at the present time. The COVID-19 pandemic has been difficult to prevent, as the infection is spread by respiratory droplets and thus effective, scalable and safe preventive interventions are urgently needed. We hypothesise that preventing viral entry into mammalian nasal epithelial cells may be one way to limit the spread of COVID-19. Here we show that N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (GCPQ), a positively charged polymer that has been through an extensive Good Laboratory Practice toxicology screen, is able to reduce the infectivity of SARS-COV-2 in A549ACE2+ and Vero E6 cells with a log removal value of −3 to −4 at a concentration of 10 – 100 μg/ mL (p < 0.05 compared to untreated controls) and to limit infectivity in human airway epithelial cells at a concentration of 500 μg/ mL (p < 0.05 compared to untreated controls). GCPQ is currently being developed as a pharmaceutical excipient in nasal and ocular formulations. GCPQ’s electrostatic binding to the virus, preventing viral entry into the host cells, is the most likely mechanism of viral inhibition. Radiolabelled GCPQ studies in mice show that at a dose of 10 mg/ kg, GCPQ has a long residence time in mouse nares, with 13.1% of the injected dose identified from SPECT/CT in the nares, 24 hours after nasal dosing. With a no observed adverse effect level of 18 mg/ kg in rats, following a 28-day repeat dose study, clinical testing of this polymer, as a COVID-19 prophylactic is warranted.

Competing Interest Statement

Ijeoma F. Uchegbu and Andreas G. Schatzlein are directors of Nanomerics Ltd.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted December 10, 2020.
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SARS-CoV-2 inhibition in human airway epithelial cells using a mucoadhesive, amphiphilic chitosan that may serve as an anti-viral nasal spray
Krzysztof Pyrć, Aleksandra Milewska, Emilia Barreto Duran, Paweł Botwina, Rui Lopes, Alejandro Arenas-Pinto, Moutaz Badr, Ryan Mellor, Tammy L. Kalber, Delmiro Fernandes-Reyes, Andreas G. Schätzlein, Ijeoma F. Uchegbu
bioRxiv 2020.12.10.413609; doi: https://doi.org/10.1101/2020.12.10.413609
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SARS-CoV-2 inhibition in human airway epithelial cells using a mucoadhesive, amphiphilic chitosan that may serve as an anti-viral nasal spray
Krzysztof Pyrć, Aleksandra Milewska, Emilia Barreto Duran, Paweł Botwina, Rui Lopes, Alejandro Arenas-Pinto, Moutaz Badr, Ryan Mellor, Tammy L. Kalber, Delmiro Fernandes-Reyes, Andreas G. Schätzlein, Ijeoma F. Uchegbu
bioRxiv 2020.12.10.413609; doi: https://doi.org/10.1101/2020.12.10.413609

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