1887

Abstract

A novel proprietary formulation, ViruSAL, has previously been demonstrated to inhibit diverse enveloped viral infections and . We evaluated the ability of ViruSAL to inhibit SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) infectivity using physiologically relevant models of the human bronchial epithelium, to model early infection of the upper respiratory tract. ViruSAL potently inhibited SARS-CoV-2 infection of human bronchial epithelial cells cultured as an air–liquid interface (ALI) model, in a concentration- and time-dependent manner. Viral infection was completely inhibited when ViruSAL was added to bronchial airway models prior to infection. Importantly, ViruSAL also inhibited viral infection when added to ALI models post-infection. No evidence of cellular toxicity was detected in ViruSAL-treated cells at concentrations that completely abrogated viral infectivity. Moreover, intranasal instillation of ViruSAL to a rat model did not result in any toxicity or pathological changes. Together these findings highlight the potential for ViruSAL as a novel and potent antiviral for use within clinical and prophylactic settings.

Funding
This study was supported by the:
  • Irish Research Council for Science, Engineering and Technology (Award GOIPG/2019/4432)
    • Principle Award Recipient: SophieO'Reilly
  • UCD Foundation (Award 000)
    • Principle Award Recipient: NicolaF Fletcher
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.001821
2023-02-14
2024-07-23
Loading full text...

Full text loading...

/deliver/fulltext/jgv/104/2/jgv001821.html?itemId=/content/journal/jgv/10.1099/jgv.0.001821&mimeType=html&fmt=ahah

References

  1. Bridges JP, Vladar EK, Huang H, Mason RJ. Respiratory epithelial cell responses to SARS-CoV-2 in COVID-19. Thorax 2022; 77:203–209 [View Article] [PubMed]
    [Google Scholar]
  2. Jia HP, Look DC, Shi L, Hickey M, Pewe L et al. ACE2 receptor expression and severe acute respiratory syndrome coronavirus infection depend on differentiation of human airway epithelia. J Virol 2005; 79:14614–14621 [View Article] [PubMed]
    [Google Scholar]
  3. Guo W, Porter LM, Crozier TW, Coates M, Jha A et al. Topical TMPRSS2 inhibition prevents SARS-CoV-2 infection in differentiated human airway cultures. Life Sci Alliance 2022; 5:e202101116 [View Article]
    [Google Scholar]
  4. Hui KPY, Ho JCW, Cheung M-C, Ng K-C, Ching RHH et al. SARS-CoV-2 Omicron variant replication in human bronchus and lung ex vivo. Nature 2022; 603:715–720 [View Article] [PubMed]
    [Google Scholar]
  5. Peacock TP et al. The SARS-cov-2 variant, omicron, shows rapid replication in human primary nasal epithelial cultures and efficiently uses the endosomal route of entry. bioRxiv 2021 [View Article]
    [Google Scholar]
  6. Hui KPY, Ng K-C, Ho JCW, Yeung H-W, Ching RHH et al. Replication of SARS-CoV-2 Omicron BA.2 variant in ex vivo cultures of the human upper and lower respiratory tract. EBioMedicine 2022; 83:104232 [View Article]
    [Google Scholar]
  7. Du X, Tang H, Gao L, Wu Z, Meng F et al. Omicron adopts a different strategy from Delta and other variants to adapt to host. Signal Transduct Target Ther 2022; 7:45 [View Article] [PubMed]
    [Google Scholar]
  8. Wölfel R, Corman VM, Guggemos W, Seilmaier M, Zange S et al. Virological assessment of hospitalized patients with COVID-2019. Nature 2020; 581:465–469 [View Article] [PubMed]
    [Google Scholar]
  9. Ratcliffe NA, Castro HC, Paixão IC, Evangelho VGO, Azambuja P et al. Nasal therapy-the missing link in optimising strategies to improve prevention and treatment of COVID-19. PLoS Pathog 2021; 17:e1010079 [View Article]
    [Google Scholar]
  10. Fletcher NF, Meredith LW, Tidswell EL, Bryden SR, Gonçalves-Carneiro D et al. A novel antiviral formulation inhibits A range of enveloped viruses. J Gen Virol 2020; 101:1090–1102 [View Article] [PubMed]
    [Google Scholar]
  11. Reed LJ, Muench H. A simple method of estimating fifty percent endpoints. Am J Hyg 1938; 27:493–497 [View Article]
    [Google Scholar]
  12. Mallon PWG, Crispie F, Gonzalez G, Tinago W, Garcia Leon AA et al. Whole-genome sequencing of SARS-CoV-2 in the Republic of Ireland during waves 1 and 2 of the pandemic. Infect Dis 2021 [View Article]
    [Google Scholar]
  13. Matsuyama S, Nao N, Shirato K, Kawase M, Saito S et al. Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. Proc Natl Acad Sci 2020; 117:7001–7003 [View Article]
    [Google Scholar]
  14. Sala-Comorera L, Reynolds LJ, Martin NA, O’Sullivan JJ, Meijer WG et al. Decay of infectious SARS-CoV-2 and surrogates in aquatic environments. Water Res 2021; 201:117090 [View Article] [PubMed]
    [Google Scholar]
  15. Mendonça L, Howe A, Gilchrist JB, Sheng Y, Sun D et al. Correlative multi-scale cryo-imaging unveils SARS-CoV-2 assembly and egress. Nat Commun 2021; 12:4629 [View Article] [PubMed]
    [Google Scholar]
  16. RR M. eds In Monographs on Pathology of Laboratory Animals: Urinary System Springer; 1998 pp 306–309
    [Google Scholar]
  17. Chitalia VC, Munawar AH. A painful lesson from the COVID-19 pandemic: the need for broad-spectrum, host-directed antivirals. J Transl Med 2020; 18:390 [View Article] [PubMed]
    [Google Scholar]
  18. Liu J, Li Y, Liu Q, Yao Q, Wang X et al. SARS-CoV-2 cell tropism and multiorgan infection. Cell Discov 2021; 7:17 [View Article] [PubMed]
    [Google Scholar]
  19. Sims AC, Burkett SE, Yount B, Pickles RJ. SARS-CoV replication and pathogenesis in an in vitro model of the human conducting airway epithelium. Virus Res 2008; 133:33–44 [View Article] [PubMed]
    [Google Scholar]
  20. Zhu N, Wang W, Liu Z, Liang C, Wang W et al. Morphogenesis and cytopathic effect of SARS-CoV-2 infection in human airway epithelial cells. Nat Commun 2020; 11:3910 [View Article]
    [Google Scholar]
  21. Do TND, Donckers K, Vangeel L, Chatterjee AK, Gallay PA et al. A robust SARS-CoV-2 replication model in primary human epithelial cells at the air liquid interface to assess antiviral agents. Antiviral Res 2021; 192:105122 [View Article]
    [Google Scholar]
  22. Pizzorno A, Padey B, Julien T, Trouillet-Assant S, Traversier A et al. Characterization and treatment of SARS-CoV-2 in nasal and bronchial human airway epithelia. Cell Rep Med 2020; 1:100059 [View Article]
    [Google Scholar]
  23. Klein S, Cortese M, Winter SL, Wachsmuth-Melm M, Neufeldt CJ et al. SARS-CoV-2 structure and replication characterized by in situ cryo-electron tomography. Nat Commun 2020; 11:5885 [View Article] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.001821
Loading
/content/journal/jgv/10.1099/jgv.0.001821
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error