Long-acting nanoparticulate DNase-1 for effective suppression of SARS-CoV-2-mediated neutrophil activities and cytokine storm.

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.

• Authors: Yun Young Lee, Hee Ho Park, Wooram Park, Hyelim Kim, Jong Geol Jang, Kyung Soo Hong, Jae-Young Lee, Hee Seung Seo, Dong Hee Na, Tae-Hyung Kim, Young Bin Choy, June Hong Ahn, Wonhwa Lee, Chun Gwon Park
• Journal: Biomaterials (Biomaterials) Vol. 267 Pg. 120389 (01 2021) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 33130319 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Ltd. All rights reserved.

Chemical References

• Drug Carriers
• Indoles
• NF-kappa B
• Polymers
• poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer
• polydopamine
• Polyglactin 910
• Polyethylene Glycols
• Dexamethasone
• DNA
• MPO protein, human
• Peroxidase
• Deoxyribonuclease I

Topics

• Animals
• COVID-19 (blood, complications, immunology)
• Cytokine Release Syndrome (drug therapy, etiology)
• DNA (blood)
• Deoxyribonuclease I (administration & dosage, therapeutic use)
• Dexamethasone (therapeutic use)
• Disease Models, Animal
• Drug Carriers (administration & dosage)
• Drug Evaluation, Preclinical
• Extracellular Traps (drug effects)
• Humans
• Indoles
• Male
• Mice
• Mice, Inbred C57BL
• Multiple Organ Failure (blood, etiology, prevention & control)
• NF-kappa B (blood)
• Nanoparticles (administration & dosage)
• Neutrophils (drug effects, enzymology)
• Peroxidase (blood)
• Polyethylene Glycols
• Polyglactin 910
• Polymers
• SARS-CoV-2
• Sepsis (drug therapy, etiology, immunology)