Abstract
Original language | English |
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DOIs | |
State | Published - 2021 |
Publication series
Name | ResearchSquare |
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Publisher | ResearchSquare |
Keywords
- COVID-19
- Drug Delivery
- General Cell Biology & Physiology
- Infectious Diseases
- Inflammation
- Metabolism
- SARS-CoV-2
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Research output: Working paper › Preprint
TY - UNPB
T1 - Metabolic Regulation of SARS-CoV-2 Infection
AU - Ehrlich, A.
AU - Ioannidis, K.
AU - Nasar, M.
AU - Alkian, I.A.
AU - Hofree, M.
AU - Tikva, S.S.
AU - Rainy, N.
AU - Houri, I.
AU - Cicero, A.
AU - Pavanello, C.
AU - Sirtori, C.R.
AU - Cohen, J.B.
AU - Chirinos, J.A.
AU - Deutsch, L.
AU - Gottlieb, A.
AU - Bar-Chaim, A.
AU - Shibolet, O.
AU - Maayan, S.L.
AU - Nahmias, Y.
N1 - Export Date: 27 November 2022 Correspondence Address: Nahmias, Y.; Hebrew University of Jerusalememail: [email protected] References: Grasselli, G., Pathophysiology of COVID-19-associated acute respiratory distress syndrome: a multicentre prospective observational study (2020) The Lancet Respiratory Medicine, 8, pp. 1201-1208; Bornstein, S. R., Dalan, R., Hopkins, D., Mingrone, G., Boehm, B. O., Endocrine and metabolic link to coronavirus infection (2020) Nature Reviews Endocrinology; Zhu, L., Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes (2020) Cell Metabolism, , https://doi.org/10.1016/j.cmet.2020.04.021; Ko, J. Y., Risk Factors for COVID-19-associated hospitalization: COVID-19Associated Hospitalization Surveillance Network and Behavioral Risk Factor Surveillance System (2020) Clin Infect Dis; Williamson, E. 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PY - 2021
Y1 - 2021
N2 - Viruses are efficient metabolic engineers that actively rewire host metabolic pathways to support their lifecycle, presenting attractive metabolic targets for intervention. Here we chart the metabolic response of lung epithelial cells to SARS-CoV-2 infection in primary cultures and COVID-19 patient samples. Bulk and single-cell analyses show that viral replication induces endoplasmic stress and lipid accumulation. Protein expression screen suggests a role for viral proteins in mediating this metabolic response even in the absence of replication. Metabolism-focused drug screen showed that fenofibrate reversed lipid accumulation and blocked SARS-CoV-2 replication. Analysis of 3,233 Israeli patients hospitalized due to COVID-19 supported in vitro findings. Patients taking fibrates showed significantly lower markers of immunoinflammation and faster recovery. Additional corroboration was received by comparative epidemiological analysis from cohorts in Europe and the United States. A subsequent prospective interventional open-label study was carried out in 15 patients hospitalized with severe COVID-19. The patients were treated with 145 mg/day of nanocrystallized fenofibrate (TriCor®) in addition to standard-of-care. Patients receiving fenofibrate demonstrated a rapid reduction in inflammation and a significantly faster recovery compared to control patients admitted during the same period and treated with the standard-of-care. Taken together, our data show that elevated lipid metabolism underlies critical aspects of COVID-19 pathogenesis, suggesting that pharmacological modulation of lipid metabolism should be strongly considered for the treatment of coronavirus infection. © 2021, CC BY.
AB - Viruses are efficient metabolic engineers that actively rewire host metabolic pathways to support their lifecycle, presenting attractive metabolic targets for intervention. Here we chart the metabolic response of lung epithelial cells to SARS-CoV-2 infection in primary cultures and COVID-19 patient samples. Bulk and single-cell analyses show that viral replication induces endoplasmic stress and lipid accumulation. Protein expression screen suggests a role for viral proteins in mediating this metabolic response even in the absence of replication. Metabolism-focused drug screen showed that fenofibrate reversed lipid accumulation and blocked SARS-CoV-2 replication. Analysis of 3,233 Israeli patients hospitalized due to COVID-19 supported in vitro findings. Patients taking fibrates showed significantly lower markers of immunoinflammation and faster recovery. Additional corroboration was received by comparative epidemiological analysis from cohorts in Europe and the United States. A subsequent prospective interventional open-label study was carried out in 15 patients hospitalized with severe COVID-19. The patients were treated with 145 mg/day of nanocrystallized fenofibrate (TriCor®) in addition to standard-of-care. Patients receiving fenofibrate demonstrated a rapid reduction in inflammation and a significantly faster recovery compared to control patients admitted during the same period and treated with the standard-of-care. Taken together, our data show that elevated lipid metabolism underlies critical aspects of COVID-19 pathogenesis, suggesting that pharmacological modulation of lipid metabolism should be strongly considered for the treatment of coronavirus infection. © 2021, CC BY.
KW - COVID-19
KW - Drug Delivery
KW - General Cell Biology & Physiology
KW - Infectious Diseases
KW - Inflammation
KW - Metabolism
KW - SARS-CoV-2
U2 - https://doi.org/10.21203/rs.3.rs-770724
DO - https://doi.org/10.21203/rs.3.rs-770724
M3 - نسخة اولية
T3 - ResearchSquare
BT - Metabolic Regulation of SARS-CoV-2 Infection
ER -