Long-acting nanoparticulate DNase-1 for effective suppression of SARS-CoV-2-mediated neutrophil activities and cytokine storm
- Authors
- Lee, Y.Y.; Park, H.H.; Park, W.; Kim, H.; Jang, J.G.; Hong, K.S.; Lee, J.-Y.; Seo, H.S.; Na, Dong Hee; Kim, Tae-Hyung; Choy, Y.B.; Ahn, J.H.; Lee, W.; Park, C.G.
- Issue Date
- Jan-2021
- Publisher
- Elsevier Ltd
- Keywords
- COVID-19; DNase; Nanoparticles; NETosis; Sepsis
- Citation
- Biomaterials, v.267
- Journal Title
- Biomaterials
- Volume
- 267
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/43437
- DOI
- 10.1016/j.biomaterials.2020.120389
- ISSN
- 0142-9612
1878-5905
- Abstract
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new strain of coronavirus not previously identified in humans. Globally, the number of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) have risen dramatically. Currently, there are no FDA-approved antiviral drugs and there is an urgency to develop treatment strategies that can effectively suppress SARS-CoV-2-mediated cytokine storms, acute respiratory distress syndrome (ARDS), and sepsis. As symptoms progress in patients with SARS-CoV-2 sepsis, elevated amounts of cell-free DNA (cfDNA) are produced, which in turn induce multiple organ failure in these patients. Furthermore, plasma levels of DNase-1 are markedly reduced in SARS-CoV-2 sepsis patients. In this study, we generated recombinant DNase-1-coated polydopamine-poly(ethylene glycol) nanoparticulates (named long-acting DNase-1), and hypothesized that exogenous administration of long-acting DNase-1 may suppress SARS-CoV-2-mediated neutrophil activities and the cytokine storm. Our findings suggest that exogenously administered long-acting nanoparticulate DNase-1 can effectively reduce cfDNA levels and neutrophil activities and may be used as a potential therapeutic intervention for life-threatening SARS-CoV-2-mediated illnesses. © 2020 Elsevier Ltd
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