期刊
BIOMATERIALS
卷 267, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2020.120389
关键词
COVID-19; Sepsis; DNase; Nanoparticles; NETosis
资金
- National Research Foundation of Korea (NRF) - Korea government (MSIT) [2019R1C1C1006300, 2019R1A4A1028700, 2018R1C1B6001120, 2018M3A7B4071204, 2020R1A4A3078645, 2020R1A4A4079817]
- BK21 FOUR Project
SARS-CoV-2 infection can lead to cytokine storm and multi-organ failure, but exogenously administered long-acting DNase-1 can effectively reduce cfDNA levels and neutrophil activities, potentially serving as a therapeutic intervention for life-threatening SARS-CoV-2-mediated illnesses.
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.
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