한빛사 논문
Hee Ho Parka,1, Hyelim Kimb,c,1, Han Sol Leeb,1, Eun U. Seoc,d,1, Ji-Eun Kimb,e,1, Jee-Hyun Leee, Yong-Hyeon Munb, So-Yeol Yoob, Jiseon Anb, Mi-Young Yunf, Nae-Won Kangg, Dae-Duk Kimg, Dong Hee Nah, Kyung Soo Hongi, Jong Geol Jangi, June Hong Ahni, Jong-Sup Baej,*, Gyu Yong Songb,e,*, Jae-Young Leeb,*, Hong Nam Kimc,d,*, Wonhwa Leek,*
aDepartment of Biotechnology and Bioengineering, Kangwon National University, Chuncheon, Gangwon-do 24341, Republic of Korea
bCollege of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea
cBrain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea
dDivision of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Republic of Korea
eAREZ Co. Ltd., Daejeon 34134, Republic of Korea
fDepartment of Beauty Science, Kwangju Women’s University, Gwangju, 62396, Republic of Korea
gCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea
hCollege of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea
iDivision of Pulmonology and Allergy, Department of Internal Medicine, College of Medicine, Yeungnam University and Regional Center for Respiratory Diseases, Yeungnam University Medical Center, Daegu 42415, Republic of Korea
jCollege of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of Korea
kAging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea
1These authors contributed equally to this study: Hee Ho Park, Hyelim Kim, Han Sol Lee, Eun U Seo, Ji-Eun Kim
*Corresponding author.
Abstract
The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on a global scale urges prompt and effective countermeasures. Recently, a study has reported that coronavirus disease-19 (COVID-19), the disease caused by SARS-CoV-2 infection, is associated with a decrease in albumin level, an increase in NETosis, blood coagulation, and cytokine level. Here, we present drug-loaded albumin nanoparticles as a therapeutic agent to resolve the clinical outcomes observed in severe SARS-CoV-2 patients. PEGylated nanoparticle albumin-bound (PNAB) was used to promote prolonged bioactivity of steroidal ginsenoside saponins, PNAB-Rg6 and PNAB-Rgx365. Our data indicate that the application of PNAB-steroidal ginsenoside can effectively reduce histone H4 and NETosis-related factors in the plasma, and alleviate SREBP2-mediated systemic inflammation in the PBMCs of SARS-CoV-2 ICU patients. The engineered blood vessel model confirmed that these drugs are effective in suppressing blood clot formation and vascular inflammation. Moreover, the animal model experiment showed that these drugs are effective in promoting the survival rate by alleviating tissue damage and cytokine storm. Altogether, our findings suggest that these PNAB-steroidal ginsenoside drugs have potential applications in the treatment of symptoms associated with severe SARS-CoV-2 patients, such as coagulation and cytokine storm.
Keywords : albumin, ginsenoside, COVID-19, NETosis, cytokine storm
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