Long-acting nanoparticulate DNase-1 for effective suppression of SARS-CoV-2-mediated neutrophil activities and cytokine storm.
Biomaterials
; 267: 120389, 2021 01.
Article
in English
| MEDLINE | ID: covidwho-898508
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
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
DNA
/
Drug Carriers
/
Sepsis
/
Deoxyribonuclease I
/
Nanoparticles
/
Cytokine Release Syndrome
/
SARS-CoV-2
/
COVID-19
/
Neutrophils
Type of study:
Experimental Studies
/
Observational study
/
Prognostic study
Topics:
Long Covid
/
Traditional medicine
Limits:
Animals
/
Humans
/
Male
Language:
English
Journal:
Biomaterials
Year:
2021
Document Type:
Article
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