tetano
Editor, Senior Moderator
Biomaterials
. 2020 Oct 23;267:120389.
doi: 10.1016/j.biomaterials.2020.120389. Online ahead of print.
Long-acting nanoparticulate DNase-1 for effective suppression of SARS-CoV-2-mediated neutrophil activities and cytokine storm
Yun Young Lee[SUP] 1 [/SUP], Hee Ho Park[SUP] 2 [/SUP], Wooram Park[SUP] 3 [/SUP], Hyelim Kim[SUP] 4 [/SUP], Jong Geol Jang[SUP] 5 [/SUP], Kyung Soo Hong[SUP] 5 [/SUP], Jae-Young Lee[SUP] 4 [/SUP], Hee Seung Seo[SUP] 6 [/SUP], Dong Hee Na[SUP] 7 [/SUP], Tae-Hyung Kim[SUP] 8 [/SUP], Young Bin Choy[SUP] 1 [/SUP], June Hong Ahn[SUP] 9 [/SUP], Wonhwa Lee[SUP] 10 [/SUP], Chun Gwon Park[SUP] 11 [/SUP]
Affiliations
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.
Keywords: COVID-19; DNase; NETosis; Nanoparticles; Sepsis.
. 2020 Oct 23;267:120389.
doi: 10.1016/j.biomaterials.2020.120389. Online ahead of print.
Long-acting nanoparticulate DNase-1 for effective suppression of SARS-CoV-2-mediated neutrophil activities and cytokine storm
Yun Young Lee[SUP] 1 [/SUP], Hee Ho Park[SUP] 2 [/SUP], Wooram Park[SUP] 3 [/SUP], Hyelim Kim[SUP] 4 [/SUP], Jong Geol Jang[SUP] 5 [/SUP], Kyung Soo Hong[SUP] 5 [/SUP], Jae-Young Lee[SUP] 4 [/SUP], Hee Seung Seo[SUP] 6 [/SUP], Dong Hee Na[SUP] 7 [/SUP], Tae-Hyung Kim[SUP] 8 [/SUP], Young Bin Choy[SUP] 1 [/SUP], June Hong Ahn[SUP] 9 [/SUP], Wonhwa Lee[SUP] 10 [/SUP], Chun Gwon Park[SUP] 11 [/SUP]
Affiliations
- PMID: 33130319
- DOI: 10.1016/j.biomaterials.2020.120389
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.
Keywords: COVID-19; DNase; NETosis; Nanoparticles; Sepsis.