All Studies Meta Analysis

Development of nanoparticles incorporated with quercetin and ACE2-membrane as a novel therapy for COVID-19

Fang et al., Journal of Nanobiotechnology, doi:10.1186/s12951-024-02435-2

Apr 2024

Post
Facebook

Source PDF All Studies Meta AnalysisMeta

Quercetin for COVID-19

24th treatment shown to reduce risk in July 2021, now with p = 0.002 from 12 studies.

Lower risk for ICU, hospitalization, recovery, cases, and viral clearance.

No treatment is 100% effective. Protocols combine treatments.

5,100+ studies for 112 treatments. c19early.org

In Vitro study showing that nanoparticles coated with both ACE2-containing cell membranes and quercetin (CM-NP-Q) inhibit SARS-CoV-2 infection in human lung cells. Authors developed nanoparticles incorporated with quercetin (NP-Q), ACE2-containing cell membranes (CM-NP), or both (CM-NP-Q). CM-NP-Q showed the strongest antiviral activity by neutralizing extracellular pseudo-SARS-CoV-2 virus in ACE2-expressing H1975, 293T, and BEAS-2B cells, and inhibiting infection of H1299 lung cancer cells by both pseudo-SARS-CoV-2 and SARS-CoV-2/NTU13 virus. NP-Q and free quercetin also inhibited viral infection, but CM-NP-Q was most effective. The enhanced activity of CM-NP-Q is attributed to its ability to both neutralize extracellular virus through its ACE2-containing membrane and inhibit viral entry through quercetin's suppression of the AXL receptor. CM-NP-Q showed no significant cytotoxicity or in vivo toxicity in mice. The results suggest CM-NP-Q has potential as an inhaled therapy to prevent SARS-CoV-2 infection.

Bioavailability. Quercetin has low bioavailability and studies typically use advanced formulations to improve bioavailability which may be required to reach therapeutic concentrations.

2 studies investigate novel formulations of quercetin for improved efficacy1,2

Important missing comments or errors? Let us know.

1. Vaiss et al., Curcumin and quercetin co-encapsulated in nanoemulsions for nasal administration: a promising therapeutic and prophylactic treatment for viral respiratory infections, European Journal of Pharmaceutical Sciences, doi:10.1016/j.ejps.2024.106766.sciencedirect.com, doi.org.

2. Fang et al., Development of nanoparticles incorporated with quercetin and ACE2-membrane as a novel therapy for COVID-19, Journal of Nanobiotechnology, doi:10.1186/s12951-024-02435-2.biomedcentral.com, doi.org.

Fang et al., 12 Apr 2024, peer-reviewed, 11 authors. Contact: pcyang@ntu.edu.tw, cychen@mail.cgust.edu.tw.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

This Paper Quercetin All

Development of nanoparticles incorporated with quercetin and ACE2-membrane as a novel therapy for COVID-19

Jia-You Fang, Kuo-Yen Huang, Tong-Hong Wang, Zih-Chan Lin, Chin-Chuan Chen, Sui-Yuan Chang, En-Li Chen, Tai-Ling Chao, Shuenn-Chen Yang, Pan-Chyr Yang, Chi-Yuan Chen

Journal of Nanobiotechnology, doi:10.1186/s12951-024-02435-2

Introduction Angiotensin-converting enzyme 2 (ACE2) and AXL tyrosine kinase receptor are known to be involved in the SARS-CoV-2 entry of the host cell. Therefore, targeting ACE2 and AXL should be an effective strategy to inhibit virus entry into cells. However, developing agents that can simultaneously target ACE2 and AXL remains a formidable task. The natural compound quercetin has been shown to inhibit AXL expression. Materials and methods In this study, we employed PLGA nanoparticles to prepare nanoparticles encapsulated with quercetin, coated with ACE2-containing cell membranes, or encapsulated with quercetin and then coated with ACE-2-containing cell membranes. These nanoparticles were tested for their abilities to neutralize or inhibit viral infection. Results Our data showed that nanoparticles encapsulated with quercetin and then coated with ACE2-containing cell membrane inhibited the expression of AXL without causing cytotoxic activity. Nanoparticles incorporated with both quercetin and ACE2-containing cell membrane were found to be able to neutralize pseudo virus infection and were more effective than free quercetin and nanoparticles encapsulated with quercetin at inhibition of pseudo virus and SARS-CoV-2 infection. Conclusions We have shown that the biomimetic nanoparticles incorporated with both ACE-2 membrane and quercetin showed the most antiviral activity and may be further explored for clinical application.

Data availability All data generated for this study are included in the article. Declarations Ethics approval and consent to participate The study involving SARS-CoV-2 was approved by the National Taiwan University Hospital Research Ethics Committee (202002002RIND). All of the mouse experiments were approved by the Institutional Animal Care and Use Committee (IACUC) of Chang Gung University (IACUC approval no.: CGU110-015) and Chang Gung Memorial Hospital (IACUC approval no.: 2020121704). Consent for publication Not applicable. Competing interests The authors declare no competing interests. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

Abian, Ortega-Alarcon, Jimenez-Alesanco, Ceballos-Laita, Vega et al., Structural stability of SARS-CoV-2 3CLpro and identification of quercetin as an inhibitor by experimental screening, Int J Biol Macromol

Anwer, Al-Mansoor, Jamil, Al-Shdefat, Ansari et al., Development and evaluation of PLGA Polymer based nanoparticles of quercetin, Int J Biol Macromol

Bhowmik, Nandi, Prakash, Kumar, Evaluation of flavonoids as 2019-nCoV cell entry inhibitor through molecular docking and pharmacological analysis, Heliyon

Bohan, Van Ert, Ruggio, Rogers, Badreddine et al., Phosphatidylserine receptors enhance SARS-CoV-2 infection, PLoS Pathog

Boots, Haenen, Bast, Health effects of quercetin: from antioxidant to nutraceutical, Eur J Pharmacol

Bouhaddou, Memon, Meyer, White, Rezelj et al., The Global Phosphorylation Landscape of SARS-CoV-2 infection, Cell

Cantuti-Castelvetri, Ojha, Pedro, Djannatian, Franz et al., Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity, Science

Chen, Huang, Law, Chu, Chen et al., Biodegradable polymers for gene-delivery applications, Int J Nanomed

Chen, Jan, Lo, Yang, Chang et al., Tid1-L inhibits EGFR signaling in lung adenocarcinoma by enhancing EGFR Ubiquitinylation and degradation, Cancer Res

Clausen, Sandoval, Spliid, Pihl, Perrett et al., SARS-CoV-2 infection depends on Cellular Heparan Sulfate and ACE2, Cell

Han, Wang, Cai, Liu, Zhang et al., Quercetin nanoparticles with enhanced bioavailability as multifunctional agents toward amyloid induced neurotoxicity, J Mater Chem B

Holland, Pan, Franci, Hu, Chang et al., R428, a selective small molecule inhibitor of Axl kinase, blocks tumor spread and prolongs survival in models of metastatic breast cancer, Cancer Res

Holzer, Vogel, Mantele, Schwartz, Haase et al., Physico-chemical characterisation of PLGA nanoparticles after freeze-drying and storage, Eur J Pharm Biopharm

Hoshyar, Gray, Han, Bao, The effect of nanoparticle size on in vivo pharmacokinetics and cellular interaction, Nanomed (Lond)

Huang, Lin, Kuo, Chen, Lin et al., Humanized COVID-19 decoy antibody effectively blocks viral entry and prevents SARS-CoV-2 infection, EMBO Mol Med

Huang, Wang, Chen, Leu, Li et al., Growth suppression in Lung Cancer cells harboring EGFR-C797S mutation by Quercetin, Biomolecules

Kamel, Helmy, Abdelfattah, Khattab, Ragab et al., Inhalable dual-targeted hybrid lipid nanocore-protein Shell composites for Combined Delivery of Genistein and All-Trans Retinoic Acid to Lung Cancer cells, ACS Biomater Sci Eng

Lee, Song, Oh, Lee, Kim et al., ERK1/2 activation in quercetin-treated BEAS-2B cell plays a role in Nrf2-driven HO-1 expression, Mol Cell Toxicol

Lee, Yoo, Simultaneous inactivation of GSK-3beta suppresses quercetin-induced apoptosis by inhibiting the JNK pathway, Am J Physiol Lung Cell Mol Physiol

Leu, Wang, Wu, Huang, Jiang et al., Hydroxygenkwanin suppresses Non-small Cell Lung Cancer Progression by enhancing EGFR Degradation, Molecules

Liu, Yu, Lin, Elzoghby, Hwang et al., Use of cilomilastloaded phosphatiosomes to suppress neutrophilic inflammation for attenuating acute lung injury: the effect of nanovesicular surface charge, J Nanobiotechnol

Mitchell, Billingsley, Haley, Wechsler, Peppas et al., Engineering precision nanoparticles for drug delivery, Nat Rev Drug Discov

Mukherjee, Khuda-Bukhsh, Quercetin Down-regulates IL-6/STAT-3 signals to induce mitochondrial-mediated apoptosis in a nonsmall-cell lungcancer cell line, A549, J Pharmacopunct

Oh, Ambigaipalan, Shahidi, Preparation of Quercetin Esters and their antioxidant activity, J Agric Food Chem

Pierro, Derosa, Maffioli, Bertuccioli, Togni et al., Possible therapeutic effects of Adjuvant Quercetin Supplementation against early-stage COVID-19 infection: a prospective, randomized, controlled, and open-label study, Int J Gen Med

Pool, Quintanar, Figueroa, Mano, Bechara et al., Antioxidant effects of Quercetin and Catechin Encapsulated into PLGA nanoparticles, J Nanomaterials

Prutskij, Deriabina, Melendez, Castro, Trejo et al., Concentration-dependent fluorescence Emission of Quercetin, Chemosensors

Rai, Tiwari, Singh, Singh, Mishra et al., Exploring the Paradox of COVID-19 in Neurological Complications with Emphasis on Parkinson's and Alzheimer's Disease, Oxid Med Cell Longev

Rayson, Lupichuk, Potvin, Dent, Shenkier et al., Canadian Cancer trials Group IND197: a phase II study of foretinib in patients with estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2-negative recurrent or metastatic breast cancer, Breast Cancer Res Treat

Rockx, Kuiken, Herfst, Bestebroer, Lamers et al., Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model, Science

Rosita, Ambarwati, Erawati, Hariyadi, Characterization and in vitro release of inhalation quercetin solid lipid microparticles: Effect of lipid, J Adv Pharm Technol Res

Sadarangani, Marchant, Kollmann, Immunological mechanisms of vaccine-induced protection against COVID-19 in humans, Nat Rev Immunol

Scalia, Haghi, Losi, Trotta, Young et al., Quercetin solid lipid microparticles: a flavonoid for inhalation lung delivery, Eur J Pharm Sci

Sheridan, First Axl inhibitor enters clinical trials, Nat Biotechnol

Singh, Bhushan, Maurya, Mishra, Singh et al., Novel coronavirus disease 2019 (COVID-19) and neurodegenerative disorders, Dermatol Ther

Singh, Maurya, Mishra, Awasthi, Dua et al., Nanovaccine: a hope to Triumph the Battle Against Novel Coronavirus Disease 2019 (COVID-19), Recent Pat Nanotechnol

Singh, Mishra, Maurya, Kulkarni, Awasthi, Biofabrication: an interesting tool to create in vitro model for COVID-19 drug targets, Med Hypotheses

Singh, Singh, Rathore, Singh, Mishra et al., Lipid-coated MCM-41 mesoporous silica nanoparticles loaded with Berberine Improved Inhibition of Acetylcholine Esterase and amyloid formation, ACS Biomater Sci Eng

Takashima, Matsushima, Hashimoto, Nose, Sato et al., Protective effects of intratracheally administered quercetin on lipopolysaccharide-induced acute lung injury, Respir Res

Taniguchi, Yamada, Wang, Tanimura, Adachi et al., AXL confers intrinsic resistance to osimertinib and advances the emergence of tolerant cells, Nat Commun

Tsai, Lin, Trousil, Sung, Lee et al., Proteinase K/ Retinoic acid-loaded Cationic liposomes as multifunctional anti-acne therapy to Disorganize Biofilm and regulate keratinocyte proliferation, Int J Nanomed

V'kovski, Kratzel, Steiner, Stalder, Thiel, Coronavirus biology and replication: implications for SARS-CoV-2, Nat Rev Microbiol

Wang, Qiu, Hou, Deng, Xu et al., AXL is a candidate receptor for SARS-CoV-2 that promotes infection of pulmonary and bronchial epithelial cells, Cell Res

Wang, Wu, Huang, Chuang, Hsueh et al., Profiling of subcellular EGFR interactome reveals hnRNP A3 modulates nuclear EGFR localization, Oncogenesis

Yau, Lencioni, Sukeepaisarnjaroen, Chao, Yen et al., A phase I/II Multicenter Study of single-Agent Foretinib as First-Line therapy in patients with Advanced Hepatocellular Carcinoma, Clin Cancer Res

Zhang, Honko, Zhou, Gong, Downs et al., Cellular Nanosponges inhibit SARS-CoV-2 infectivity, Nano Lett

Zhang, Xiang, Huo, Zhou, Jiang et al., Molecular mechanism of interaction between SARS-CoV-2 and host cells and interventional therapy, Signal Transduct Target Ther

Zhao, Chen, Wu, Wang, Du et al., Highly efficient photothermal nanoagent achieved by harvesting energy via excited-state intramolecular motion within nanoparticles, Nat Commun

Zhao, Yuan, Meng, Qiu, Wang, Quercetin-loaded mixed micelles exhibit enhanced cytotoxic efficacy in non-small cell lung cancer in vitro, Exp Ther Med

{ 'indexed': {'date-parts': [[2024, 4, 12]], 'date-time': '2024-04-12T13:41:27Z', 'timestamp': 1712929287125}, 'reference-count': 49, 'publisher': 'Springer Science and Business Media LLC', 'issue': '1', 'license': [ { 'start': { 'date-parts': [[2024, 4, 12]], 'date-time': '2024-04-12T00:00:00Z', 'timestamp': 1712880000000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}, { 'start': { 'date-parts': [[2024, 4, 12]], 'date-time': '2024-04-12T00:00:00Z', 'timestamp': 1712880000000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}], 'funder': [ {'name': 'National Science and Technology Council', 'award': ['NSTC 111-2124-M-002 -010']}, { 'DOI': '10.13039/100012553', 'name': 'Chang Gung Memorial Hospital', 'doi-asserted-by': 'crossref', 'award': ['CMRPF1L0052']}, { 'DOI': '10.13039/501100004663', 'name': 'Ministry of Science and Technology of Taiwan', 'doi-asserted-by': 'crossref', 'award': ['MOST 111-2320-B-255-003']}, {'name': 'Chang Gung University of Science and Technology', 'award': ['ZRRPF3M0091']}], 'content-domain': {'domain': ['link.springer.com'], 'crossmark-restriction': False}, 'abstract': 'Abstract\n' ' Introduction\n' ' Angiotensin-converting enzyme 2 (ACE2) and AXL tyrosine kinase ' 'receptor are known to be involved in the SARS-CoV-2 entry of the host cell. Therefore, ' 'targeting ACE2 and AXL should be an effective strategy to inhibit virus entry into cells. ' 'However, developing agents that can simultaneously target ACE2 and AXL remains a formidable ' 'task. The natural compound quercetin has been shown to inhibit AXL expression.\n' ' \n' ' Materials and methods\n' ' In this study, we employed PLGA nanoparticles to prepare ' 'nanoparticles encapsulated with quercetin, coated with ACE2-containing cell membranes, or ' 'encapsulated with quercetin and then coated with ACE-2-containing cell membranes. These ' 'nanoparticles were tested for their abilities to neutralize or inhibit viral ' 'infection.\n' ' \n' ' Results\n' ' Our data showed that nanoparticles encapsulated with quercetin and ' 'then coated with ACE2-containing cell membrane inhibited the expression of AXL without ' 'causing cytotoxic activity. Nanoparticles incorporated with both quercetin and ' 'ACE2-containing cell membrane were found to be able to neutralize pseudo virus infection and ' 'were more effective than free quercetin and nanoparticles encapsulated with quercetin at ' 'inhibition of pseudo virus and SARS-CoV-2 infection.\n' ' \n' ' Conclusions\n' ' We have shown that the biomimetic nanoparticles incorporated with ' 'both ACE-2 membrane and quercetin showed the most antiviral activity and may be further ' 'explored for clinical application.\n' ' ', 'DOI': '10.1186/s12951-024-02435-2', 'type': 'journal-article', 'created': {'date-parts': [[2024, 4, 12]], 'date-time': '2024-04-12T13:01:53Z', 'timestamp': 1712926913000}, 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Development of nanoparticles incorporated with quercetin and ACE2-membrane as a novel therapy ' 'for COVID-19', 'prefix': '10.1186', 'volume': '22', 'author': [ {'given': 'Jia-You', 'family': 'Fang', 'sequence': 'first', 'affiliation': []}, {'given': 'Kuo-Yen', 'family': 'Huang', 'sequence': 'additional', 'affiliation': []}, {'given': 'Tong-Hong', 'family': 'Wang', 'sequence': 'additional', 'affiliation': []}, {'given': 'Zih-Chan', 'family': 'Lin', 'sequence': 'additional', 'affiliation': []}, {'given': 'Chin-Chuan', 'family': 'Chen', 'sequence': 'additional', 'affiliation': []}, {'given': 'Sui-Yuan', 'family': 'Chang', 'sequence': 'additional', 'affiliation': []}, {'given': 'En-Li', 'family': 'Chen', 'sequence': 'additional', 'affiliation': []}, {'given': 'Tai-Ling', 'family': 'Chao', 'sequence': 'additional', 'affiliation': []}, {'given': 'Shuenn-Chen', 'family': 'Yang', 'sequence': 'additional', 'affiliation': []}, {'given': 'Pan-Chyr', 'family': 'Yang', 'sequence': 'additional', 'affiliation': []}, {'given': 'Chi-Yuan', 'family': 'Chen', 'sequence': 'additional', 'affiliation': []}], 'member': '297', 'published-online': {'date-parts': [[2024, 4, 12]]}, 'reference': [ { 'key': '2435_CR1', 'first-page': 'e13591', 'volume': '33', 'author': 'AK Singh', 'year': '2020', 'unstructured': 'Singh AK, Bhushan B, Maurya A, Mishra G, Singh SK, Awasthi R. Novel ' 'coronavirus disease 2019 (COVID-19) and neurodegenerative disorders. ' 'Dermatol Ther. 2020;33:e13591.', 'journal-title': 'Dermatol Ther'}, { 'key': '2435_CR2', 'doi-asserted-by': 'crossref', 'unstructured': 'Rai SN, Tiwari N, Singh P, Singh AK, Mishra D, Imran M, Singh S, ' 'Hooshmandi E, Vamanu E, Singh SK, Singh MP. Exploring the Paradox of ' 'COVID-19 in Neurological Complications with Emphasis on Parkinson’s and ' 'Alzheimer’s Disease. Oxid Med Cell Longev 2022, 2022:3012778.', 'DOI': '10.1155/2022/3012778'}, { 'key': '2435_CR3', 'doi-asserted-by': 'crossref', 'first-page': '155', 'DOI': '10.1038/s41579-020-00468-6', 'volume': '19', 'author': 'P V’Kovski', 'year': '2021', 'unstructured': 'V’Kovski P, Kratzel A, Steiner S, Stalder H, Thiel V. Coronavirus ' 'biology and replication: implications for SARS-CoV-2. Nat Rev Microbiol. ' '2021;19:155–70.', 'journal-title': 'Nat Rev Microbiol'}, { 'key': '2435_CR4', 'doi-asserted-by': 'crossref', 'first-page': '475', 'DOI': '10.1038/s41577-021-00578-z', 'volume': '21', 'author': 'M Sadarangani', 'year': '2021', 'unstructured': 'Sadarangani M, Marchant A, Kollmann TR. Immunological mechanisms of ' 'vaccine-induced protection against COVID-19 in humans. Nat Rev Immunol. ' '2021;21:475–84.', 'journal-title': 'Nat Rev Immunol'}, { 'key': '2435_CR5', 'first-page': '15', 'volume': '17', 'author': 'AK Singh', 'year': '2023', 'unstructured': 'Singh AK, Maurya A, Mishra G, Awasthi R, Dua K, Kulkarni GT. ' 'Nanovaccine: a hope to Triumph the Battle Against Novel Coronavirus ' 'Disease 2019 (COVID-19). Recent Pat Nanotechnol. 2023;17:15–7.', 'journal-title': 'Recent Pat Nanotechnol'}, { 'key': '2435_CR6', 'doi-asserted-by': 'crossref', 'first-page': '126', 'DOI': '10.1038/s41422-020-00460-y', 'volume': '31', 'author': 'S Wang', 'year': '2021', 'unstructured': 'Wang S, Qiu Z, Hou Y, Deng X, Xu W, Zheng T, Wu P, Xie S, Bian W, Zhang ' 'C, et al. AXL is a candidate receptor for SARS-CoV-2 that promotes ' 'infection of pulmonary and bronchial epithelial cells. Cell Res. ' '2021;31:126–40.', 'journal-title': 'Cell Res'}, { 'key': '2435_CR7', 'doi-asserted-by': 'crossref', 'first-page': '856', 'DOI': '10.1126/science.abd2985', 'volume': '370', 'author': 'L Cantuti-Castelvetri', 'year': '2020', 'unstructured': 'Cantuti-Castelvetri L, Ojha R, Pedro LD, Djannatian M, Franz J, Kuivanen ' 'S, van der Meer F, Kallio K, Kaya T, Anastasina M, et al. Neuropilin-1 ' 'facilitates SARS-CoV-2 cell entry and infectivity. Science. ' '2020;370:856–60.', 'journal-title': 'Science'}, { 'key': '2435_CR8', 'doi-asserted-by': 'crossref', 'first-page': '1043', 'DOI': '10.1016/j.cell.2020.09.033', 'volume': '183', 'author': 'TM Clausen', 'year': '2020', 'unstructured': 'Clausen TM, Sandoval DR, Spliid CB, Pihl J, Perrett HR, Painter CD, ' 'Narayanan A, Majowicz SA, Kwong EM, McVicar RN, et al. SARS-CoV-2 ' 'infection depends on Cellular Heparan Sulfate and ACE2. Cell. ' '2020;183:1043–e10571015.', 'journal-title': 'Cell'}, { 'key': '2435_CR9', 'doi-asserted-by': 'crossref', 'first-page': 'e1009743', 'DOI': '10.1371/journal.ppat.1009743', 'volume': '17', 'author': 'D Bohan', 'year': '2021', 'unstructured': 'Bohan D, Van Ert H, Ruggio N, Rogers KJ, Badreddine M, Aguilar Briseno ' 'JA, Elliff JM, Rojas Chavez RA, Gao B, Stokowy T, et al. ' 'Phosphatidylserine receptors enhance SARS-CoV-2 infection. PLoS Pathog. ' '2021;17:e1009743.', 'journal-title': 'PLoS Pathog'}, { 'key': '2435_CR10', 'doi-asserted-by': 'crossref', 'first-page': '685', 'DOI': '10.1016/j.cell.2020.06.034', 'volume': '182', 'author': 'M Bouhaddou', 'year': '2020', 'unstructured': 'Bouhaddou M, Memon D, Meyer B, White KM, Rezelj VV, Correa Marrero M, ' 'Polacco BJ, Melnyk JE, Ulferts S, Kaake RM, et al. The Global ' 'Phosphorylation Landscape of SARS-CoV-2 infection. Cell. ' '2020;182:685–e712619.', 'journal-title': 'Cell'}, { 'key': '2435_CR11', 'doi-asserted-by': 'crossref', 'first-page': '1544', 'DOI': '10.1158/0008-5472.CAN-09-2997', 'volume': '70', 'author': 'SJ Holland', 'year': '2010', 'unstructured': 'Holland SJ, Pan A, Franci C, Hu Y, Chang B, Li W, Duan M, Torneros A, Yu ' 'J, Heckrodt TJ, et al. R428, a selective small molecule inhibitor of Axl ' 'kinase, blocks tumor spread and prolongs survival in models of ' 'metastatic breast cancer. Cancer Res. 2010;70:1544–54.', 'journal-title': 'Cancer Res'}, { 'key': '2435_CR12', 'doi-asserted-by': 'crossref', 'first-page': '775', 'DOI': '10.1038/nbt0913-775a', 'volume': '31', 'author': 'C Sheridan', 'year': '2013', 'unstructured': 'Sheridan C. First Axl inhibitor enters clinical trials. Nat Biotechnol. ' '2013;31:775–6.', 'journal-title': 'Nat Biotechnol'}, { 'key': '2435_CR13', 'doi-asserted-by': 'crossref', 'first-page': '109', 'DOI': '10.1007/s10549-016-3812-1', 'volume': '157', 'author': 'D Rayson', 'year': '2016', 'unstructured': 'Rayson D, Lupichuk S, Potvin K, Dent S, Shenkier T, Dhesy-Thind S, ' 'Ellard SL, Prady C, Salim M, Farmer P, et al. Canadian Cancer trials ' 'Group IND197: a phase II study of foretinib in patients with estrogen ' 'receptor, progesterone receptor, and human epidermal growth factor ' 'receptor 2-negative recurrent or metastatic breast cancer. Breast Cancer ' 'Res Treat. 2016;157:109–16.', 'journal-title': 'Breast Cancer Res Treat'}, { 'key': '2435_CR14', 'doi-asserted-by': 'crossref', 'first-page': '2405', 'DOI': '10.1158/1078-0432.CCR-16-1789', 'volume': '23', 'author': 'TCC Yau', 'year': '2017', 'unstructured': 'Yau TCC, Lencioni R, Sukeepaisarnjaroen W, Chao Y, Yen CJ, ' 'Lausoontornsiri W, Chen PJ, Sanpajit T, Camp A, Cox DS, et al. A phase ' 'I/II Multicenter Study of single-Agent Foretinib as First-Line therapy ' 'in patients with Advanced Hepatocellular Carcinoma. Clin Cancer Res. ' '2017;23:2405–13.', 'journal-title': 'Clin Cancer Res'}, { 'key': '2435_CR15', 'doi-asserted-by': 'crossref', 'first-page': '325', 'DOI': '10.1016/j.ejphar.2008.03.008', 'volume': '585', 'author': 'AW Boots', 'year': '2008', 'unstructured': 'Boots AW, Haenen GR, Bast A. Health effects of quercetin: from ' 'antioxidant to nutraceutical. Eur J Pharmacol. 2008;585:325–37.', 'journal-title': 'Eur J Pharmacol'}, { 'key': '2435_CR16', 'doi-asserted-by': 'crossref', 'first-page': '1271', 'DOI': '10.3390/biom11091271', 'volume': '11', 'author': 'K-Y Huang', 'year': '2021', 'unstructured': 'Huang K-Y, Wang T-H, Chen C-C, Leu Y-L, Li H-J, Jhong C-L, Chen C-Y. ' 'Growth suppression in Lung Cancer cells harboring EGFR-C797S mutation by ' 'Quercetin. Biomolecules. 2021;11:1271.', 'journal-title': 'Biomolecules'}, { 'key': '2435_CR17', 'doi-asserted-by': 'crossref', 'first-page': '19', 'DOI': '10.3831/KPI.2015.18.002', 'volume': '18', 'author': 'A Mukherjee', 'year': '2015', 'unstructured': 'Mukherjee A, Khuda-Bukhsh AR. Quercetin Down-regulates IL-6/STAT-3 ' 'signals to induce mitochondrial-mediated apoptosis in a nonsmall- cell ' 'lung-cancer cell line, A549. J Pharmacopunct. 2015;18:19–26.', 'journal-title': 'J Pharmacopunct'}, { 'key': '2435_CR18', 'doi-asserted-by': 'crossref', 'first-page': '1693', 'DOI': '10.1016/j.ijbiomac.2020.07.235', 'volume': '164', 'author': 'O Abian', 'year': '2020', 'unstructured': 'Abian O, Ortega-Alarcon D, Jimenez-Alesanco A, Ceballos-Laita L, Vega S, ' 'Reyburn HT, Rizzuti B, Velazquez-Campoy A. Structural stability of ' 'SARS-CoV-2 3CLpro and identification of quercetin as an inhibitor by ' 'experimental screening. Int J Biol Macromol. 2020;164:1693–703.', 'journal-title': 'Int J Biol Macromol'}, { 'key': '2435_CR19', 'doi-asserted-by': 'crossref', 'first-page': 'e06515', 'DOI': '10.1016/j.heliyon.2021.e06515', 'volume': '7', 'author': 'D Bhowmik', 'year': '2021', 'unstructured': 'Bhowmik D, Nandi R, Prakash A, Kumar D. Evaluation of flavonoids as ' '2019-nCoV cell entry inhibitor through molecular docking and ' 'pharmacological analysis. Heliyon. 2021;7:e06515.', 'journal-title': 'Heliyon'}, { 'key': '2435_CR20', 'doi-asserted-by': 'crossref', 'first-page': '2359', 'DOI': '10.2147/IJGM.S318720', 'volume': '14', 'author': 'F Di Pierro', 'year': '2021', 'unstructured': 'Di Pierro F, Derosa G, Maffioli P, Bertuccioli A, Togni S, Riva A, ' 'Allegrini P, Khan A, Khan S, Khan BA, et al. Possible therapeutic ' 'effects of Adjuvant Quercetin Supplementation against early-stage ' 'COVID-19 infection: a prospective, randomized, controlled, and ' 'open-label study. Int J Gen Med. 2021;14:2359–66.', 'journal-title': 'Int J Gen Med'}, { 'key': '2435_CR21', 'doi-asserted-by': 'crossref', 'first-page': '1387', 'DOI': '10.1039/C7TB03053C', 'volume': '6', 'author': 'Q Han', 'year': '2018', 'unstructured': 'Han Q, Wang X, Cai S, Liu X, Zhang Y, Yang L, Wang C, Yang R. Quercetin ' 'nanoparticles with enhanced bioavailability as multifunctional agents ' 'toward amyloid induced neurotoxicity. J Mater Chem B. 2018;6:1387–93.', 'journal-title': 'J Mater Chem B'}, { 'key': '2435_CR22', 'first-page': '5503', 'volume': '14', 'author': 'MH Zhao', 'year': '2017', 'unstructured': 'Zhao MH, Yuan L, Meng LY, Qiu JL, Wang CB. Quercetin-loaded mixed ' 'micelles exhibit enhanced cytotoxic efficacy in non-small cell lung ' 'cancer in vitro. Exp Ther Med. 2017;14:5503–8.', 'journal-title': 'Exp Ther Med'}, { 'key': '2435_CR23', 'doi-asserted-by': 'crossref', 'first-page': 'L782', 'DOI': '10.1152/ajplung.00348.2012', 'volume': '304', 'author': 'KH Lee', 'year': '2013', 'unstructured': 'Lee KH, Yoo CG. Simultaneous inactivation of GSK-3beta suppresses ' 'quercetin-induced apoptosis by inhibiting the JNK pathway. Am J Physiol ' 'Lung Cell Mol Physiol. 2013;304:L782–789.', 'journal-title': 'Am J Physiol Lung Cell Mol Physiol'}, { 'key': '2435_CR24', 'doi-asserted-by': 'crossref', 'first-page': '347', 'DOI': '10.1007/s13273-011-0044-7', 'volume': '7', 'author': 'Y-J Lee', 'year': '2011', 'unstructured': 'Lee Y-J, Song J-H, Oh M-H, Lee Y-J, Kim Y-B, Im J-H, Lee S-H. ERK1/2 ' 'activation in quercetin-treated BEAS-2B cell plays a role in Nrf2-driven ' 'HO-1 expression. Mol Cell Toxicol. 2011;7:347–55.', 'journal-title': 'Mol Cell Toxicol'}, { 'key': '2435_CR25', 'doi-asserted-by': 'crossref', 'first-page': '233', 'DOI': '10.1038/s41392-021-00653-w', 'volume': '6', 'author': 'Q Zhang', 'year': '2021', 'unstructured': 'Zhang Q, Xiang R, Huo S, Zhou Y, Jiang S, Wang Q, Yu F. Molecular ' 'mechanism of interaction between SARS-CoV-2 and host cells and ' 'interventional therapy. Signal Transduct Target Ther. 2021;6:233.', 'journal-title': 'Signal Transduct Target Ther'}, { 'key': '2435_CR26', 'doi-asserted-by': 'crossref', 'first-page': '101', 'DOI': '10.1038/s41573-020-0090-8', 'volume': '20', 'author': 'MJ Mitchell', 'year': '2021', 'unstructured': 'Mitchell MJ, Billingsley MM, Haley RM, Wechsler ME, Peppas NA, Langer R. ' 'Engineering precision nanoparticles for drug delivery. Nat Rev Drug ' 'Discov. 2021;20:101–24.', 'journal-title': 'Nat Rev Drug Discov'}, { 'key': '2435_CR27', 'doi-asserted-by': 'crossref', 'first-page': '2131', 'DOI': '10.2147/IJN.S222419', 'volume': '15', 'author': 'CK Chen', 'year': '2020', 'unstructured': 'Chen CK, Huang PK, Law WC, Chu CH, Chen NT, Lo LW. Biodegradable ' 'polymers for gene-delivery applications. Int J Nanomed. 2020;15:2131–50.', 'journal-title': 'Int J Nanomed'}, { 'key': '2435_CR28', 'doi-asserted-by': 'crossref', 'first-page': '3737', 'DOI': '10.1021/acsbiomaterials.1c00514', 'volume': '7', 'author': 'AK Singh', 'year': '2021', 'unstructured': 'Singh AK, Singh SS, Rathore AS, Singh SP, Mishra G, Awasthi R, Mishra ' 'SK, Gautam V, Singh SK. Lipid-coated MCM-41 mesoporous silica ' 'nanoparticles loaded with Berberine Improved Inhibition of Acetylcholine ' 'Esterase and amyloid formation. ACS Biomater Sci Eng. 2021;7:3737–53.', 'journal-title': 'ACS Biomater Sci Eng'}, { 'key': '2435_CR29', 'doi-asserted-by': 'crossref', 'first-page': '673', 'DOI': '10.2217/nnm.16.5', 'volume': '11', 'author': 'N Hoshyar', 'year': '2016', 'unstructured': 'Hoshyar N, Gray S, Han H, Bao G. The effect of nanoparticle size on in ' 'vivo pharmacokinetics and cellular interaction. Nanomed (Lond). ' '2016;11:673–92.', 'journal-title': 'Nanomed (Lond)'}, { 'key': '2435_CR30', 'doi-asserted-by': 'crossref', 'first-page': '768', 'DOI': '10.1038/s41467-019-08722-z', 'volume': '10', 'author': 'Z Zhao', 'year': '2019', 'unstructured': 'Zhao Z, Chen C, Wu W, Wang F, Du L, Zhang X, Xiong Y, He X, Cai Y, Kwok ' 'RTK, et al. Highly efficient photothermal nanoagent achieved by ' 'harvesting energy via excited-state intramolecular motion within ' 'nanoparticles. Nat Commun. 2019;10:768.', 'journal-title': 'Nat Commun'}, { 'key': '2435_CR31', 'doi-asserted-by': 'crossref', 'first-page': '315', 'DOI': '10.3390/chemosensors9110315', 'volume': '9', 'author': 'T Prutskij', 'year': '2021', 'unstructured': 'Prutskij T, Deriabina A, Melendez FJ, Castro ME, Castillo Trejo L, ' 'Vazquez Leon GD, Gonzalez E, Perova TS. Concentration-dependent ' 'fluorescence Emission of Quercetin. Chemosensors. 2021;9:315.', 'journal-title': 'Chemosensors'}, { 'key': '2435_CR32', 'doi-asserted-by': 'crossref', 'first-page': '428', 'DOI': '10.1016/j.ejpb.2009.02.002', 'volume': '72', 'author': 'M Holzer', 'year': '2009', 'unstructured': 'Holzer M, Vogel V, Mantele W, Schwartz D, Haase W, Langer K. ' 'Physico-chemical characterisation of PLGA nanoparticles after ' 'freeze-drying and storage. Eur J Pharm Biopharm. 2009;72:428–37.', 'journal-title': 'Eur J Pharm Biopharm'}, { 'key': '2435_CR33', 'doi-asserted-by': 'crossref', 'first-page': '278', 'DOI': '10.1016/j.ejps.2013.03.009', 'volume': '49', 'author': 'S Scalia', 'year': '2013', 'unstructured': 'Scalia S, Haghi M, Losi V, Trotta V, Young PM, Traini D. Quercetin solid ' 'lipid microparticles: a flavonoid for inhalation lung delivery. Eur J ' 'Pharm Sci. 2013;49:278–85.', 'journal-title': 'Eur J Pharm Sci'}, { 'key': '2435_CR34', 'doi-asserted-by': 'crossref', 'first-page': '259', 'DOI': '10.1038/s41467-018-08074-0', 'volume': '10', 'author': 'H Taniguchi', 'year': '2019', 'unstructured': 'Taniguchi H, Yamada T, Wang R, Tanimura K, Adachi Y, Nishiyama A, ' 'Tanimoto A, Takeuchi S, Araujo LH, Boroni M, et al. AXL confers ' 'intrinsic resistance to osimertinib and advances the emergence of ' 'tolerant cells. Nat Commun. 2019;10:259.', 'journal-title': 'Nat Commun'}, { 'key': '2435_CR35', 'doi-asserted-by': 'crossref', 'first-page': '1012', 'DOI': '10.1126/science.abb7314', 'volume': '368', 'author': 'B Rockx', 'year': '2020', 'unstructured': 'Rockx B, Kuiken T, Herfst S, Bestebroer T, Lamers MM, Oude Munnink BB, ' 'de Meulder D, van Amerongen G, van den Brand J, Okba NMA, et al. ' 'Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman ' 'primate model. Science. 2020;368:1012–5.', 'journal-title': 'Science'}, { 'key': '2435_CR36', 'doi-asserted-by': 'crossref', 'first-page': '10653', 'DOI': '10.1021/acs.jafc.9b04154', 'volume': '67', 'author': 'WY Oh', 'year': '2019', 'unstructured': 'Oh WY, Ambigaipalan P, Shahidi F. Preparation of Quercetin Esters and ' 'their antioxidant activity. J Agric Food Chem. 2019;67:10653–9.', 'journal-title': 'J Agric Food Chem'}, { 'key': '2435_CR37', 'first-page': '11', 'volume': '13', 'author': 'N Rosita', 'year': '2022', 'unstructured': 'Rosita N, Ambarwati N, Erawati T, Hariyadi DM. Characterization and in ' 'vitro release of inhalation quercetin solid lipid microparticles: Effect ' 'of lipid. J Adv Pharm Technol Res. 2022;13:11–7.', 'journal-title': 'J Adv Pharm Technol Res'}, { 'key': '2435_CR38', 'doi-asserted-by': 'crossref', 'first-page': '213', 'DOI': '10.1016/j.ijbiomac.2016.07.002', 'volume': '92', 'author': 'MK Anwer', 'year': '2016', 'unstructured': 'Anwer MK, Al-Mansoor MA, Jamil S, Al-Shdefat R, Ansari MN, Shakeel F. ' 'Development and evaluation of PLGA Polymer based nanoparticles of ' 'quercetin. Int J Biol Macromol. 2016;92:213–9.', 'journal-title': 'Int J Biol Macromol'}, { 'key': '2435_CR39', 'doi-asserted-by': 'crossref', 'first-page': '145380', 'DOI': '10.1155/2012/145380', 'volume': '2012', 'author': 'H Pool', 'year': '2012', 'unstructured': 'Pool H, Quintanar D, Figueroa JD, Marinho Mano C, Bechara JEH, Godínez ' 'LA, Mendoza S. Antioxidant effects of Quercetin and Catechin ' 'Encapsulated into PLGA nanoparticles. J Nanomaterials. 2012;2012:145380.', 'journal-title': 'J Nanomaterials'}, { 'key': '2435_CR40', 'doi-asserted-by': 'crossref', 'first-page': '110059', 'DOI': '10.1016/j.mehy.2020.110059', 'volume': '144', 'author': 'AK Singh', 'year': '2020', 'unstructured': 'Singh AK, Mishra G, Maurya A, Kulkarni GT, Awasthi R. Biofabrication: an ' 'interesting tool to create in vitro model for COVID-19 drug targets. Med ' 'Hypotheses. 2020;144:110059.', 'journal-title': 'Med Hypotheses'}, { 'key': '2435_CR41', 'doi-asserted-by': 'crossref', 'first-page': 'e12828', 'DOI': '10.15252/emmm.202012828', 'volume': '13', 'author': 'KY Huang', 'year': '2021', 'unstructured': 'Huang KY, Lin MS, Kuo TC, Chen CL, Lin CC, Chou YC, Chao TL, Pang YH, ' 'Kao HC, Huang RS, et al. Humanized COVID-19 decoy antibody effectively ' 'blocks viral entry and prevents SARS-CoV-2 infection. EMBO Mol Med. ' '2021;13:e12828.', 'journal-title': 'EMBO Mol Med'}, { 'key': '2435_CR42', 'doi-asserted-by': 'crossref', 'first-page': '5570', 'DOI': '10.1021/acs.nanolett.0c02278', 'volume': '20', 'author': 'Q Zhang', 'year': '2020', 'unstructured': 'Zhang Q, Honko A, Zhou J, Gong H, Downs SN, Vasquez JH, Fang RH, Gao W, ' 'Griffiths A, Zhang L. Cellular Nanosponges inhibit SARS-CoV-2 ' 'infectivity. Nano Lett. 2020;20:5570–4.', 'journal-title': 'Nano Lett'}, { 'key': '2435_CR43', 'doi-asserted-by': 'crossref', 'first-page': '71', 'DOI': '10.1021/acsbiomaterials.8b01374', 'volume': '6', 'author': 'NM Kamel', 'year': '2020', 'unstructured': 'Kamel NM, Helmy MW, Abdelfattah EZ, Khattab SN, Ragab D, Samaha MW, Fang ' 'JY, Elzoghby AO. Inhalable dual-targeted hybrid lipid nanocore-protein ' 'Shell composites for Combined Delivery of Genistein and All-Trans ' 'Retinoic Acid to Lung Cancer cells. ACS Biomater Sci Eng. 2020;6:71–87.', 'journal-title': 'ACS Biomater Sci Eng'}, { 'key': '2435_CR44', 'doi-asserted-by': 'crossref', 'first-page': '3879', 'DOI': '10.2147/IJN.S416966', 'volume': '18', 'author': 'MJ Tsai', 'year': '2023', 'unstructured': 'Tsai MJ, Lin CY, Trousil J, Sung CT, Lee MH, Fang JY, Yang SC. ' 'Proteinase K/Retinoic acid-loaded Cationic liposomes as multifunctional ' 'anti-acne therapy to Disorganize Biofilm and regulate keratinocyte ' 'proliferation. Int J Nanomed. 2023;18:3879–96.', 'journal-title': 'Int J Nanomed'}, { 'key': '2435_CR45', 'doi-asserted-by': 'crossref', 'first-page': '35', 'DOI': '10.1186/s12951-018-0364-z', 'volume': '16', 'author': 'FC Liu', 'year': '2018', 'unstructured': 'Liu FC, Yu HP, Lin CY, Elzoghby AO, Hwang TL, Fang JY. Use of ' 'cilomilast-loaded phosphatiosomes to suppress neutrophilic inflammation ' 'for attenuating acute lung injury: the effect of nanovesicular surface ' 'charge. J Nanobiotechnol. 2018;16:35.', 'journal-title': 'J Nanobiotechnol'}, { 'key': '2435_CR46', 'doi-asserted-by': 'crossref', 'first-page': '40', 'DOI': '10.1038/s41389-020-0225-0', 'volume': '9', 'author': 'TH Wang', 'year': '2020', 'unstructured': 'Wang TH, Wu CC, Huang KY, Chuang WY, Hsueh C, Li HJ, Chen CY. Profiling ' 'of subcellular EGFR interactome reveals hnRNP A3 modulates nuclear EGFR ' 'localization. Oncogenesis. 2020;9:40.', 'journal-title': 'Oncogenesis'}, { 'key': '2435_CR47', 'doi-asserted-by': 'crossref', 'unstructured': 'Leu YL, Wang TH, Wu CC, Huang KY, Jiang YW, Hsu YC, Chen CY. ' 'Hydroxygenkwanin suppresses Non-small Cell Lung Cancer Progression by ' 'enhancing EGFR Degradation. Molecules 2020, 25.', 'DOI': '10.3390/molecules25040941'}, { 'key': '2435_CR48', 'doi-asserted-by': 'crossref', 'first-page': '4009', 'DOI': '10.1158/0008-5472.CAN-12-4066', 'volume': '73', 'author': 'CY Chen', 'year': '2013', 'unstructured': 'Chen CY, Jan CI, Lo JF, Yang SC, Chang YL, Pan SH, Wang WL, Hong TM, ' 'Yang PC. Tid1-L inhibits EGFR signaling in lung adenocarcinoma by ' 'enhancing EGFR Ubiquitinylation and degradation. Cancer Res. ' '2013;73:4009–19.', 'journal-title': 'Cancer Res'}, { 'key': '2435_CR49', 'doi-asserted-by': 'crossref', 'first-page': '150', 'DOI': '10.1186/s12931-014-0150-x', 'volume': '15', 'author': 'K Takashima', 'year': '2014', 'unstructured': 'Takashima K, Matsushima M, Hashimoto K, Nose H, Sato M, Hashimoto N, ' 'Hasegawa Y, Kawabe T. Protective effects of intratracheally administered ' 'quercetin on lipopolysaccharide-induced acute lung injury. Respir Res. ' '2014;15:150.', 'journal-title': 'Respir Res'}], 'container-title': 'Journal of Nanobiotechnology', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://link.springer.com/content/pdf/10.1186/s12951-024-02435-2.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/article/10.1186/s12951-024-02435-2/fulltext.html', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/content/pdf/10.1186/s12951-024-02435-2.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2024, 4, 12]], 'date-time': '2024-04-12T13:06:13Z', 'timestamp': 1712927173000}, 'score': 1, 'resource': { 'primary': { 'URL': 'https://jnanobiotechnology.biomedcentral.com/articles/10.1186/s12951-024-02435-2'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2024, 4, 12]]}, 'references-count': 49, 'journal-issue': {'issue': '1', 'published-online': {'date-parts': [[2024, 12]]}}, 'alternative-id': ['2435'], 'URL': 'http://dx.doi.org/10.1186/s12951-024-02435-2', 'relation': {}, 'ISSN': ['1477-3155'], 'subject': [ 'Pharmaceutical Science', 'Applied Microbiology and Biotechnology', 'Biomedical Engineering', 'Molecular Medicine', 'Medicine (miscellaneous)', 'Bioengineering'], 'container-title-short': 'J Nanobiotechnol', 'published': {'date-parts': [[2024, 4, 12]]}, 'assertion': [ { 'value': '15 October 2023', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '22 March 2024', 'order': 2, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '12 April 2024', 'order': 3, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, {'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Declarations'}}, { 'value': 'The study involving SARS-CoV-2 was approved by the National Taiwan University ' 'Hospital Research Ethics Committee (202002002RIND).', 'order': 2, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Ethics approval and consent to participate'}}, { 'value': 'All of the mouse experiments were approved by the Institutional Animal Care and ' 'Use Committee (IACUC) of Chang Gung University (IACUC approval no.: CGU110-015) ' 'and Chang Gung Memorial Hospital (IACUC approval no.: 2020121704).', 'order': 3, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Ethics approval and consent to participate'}}, { 'value': 'Not applicable.', 'order': 4, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Consent for publication'}}, { 'value': 'The authors declare no competing interests.', 'order': 5, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}], 'article-number': '169'}

Download Image

Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.

Submit

Post

@CovidAnalysis

FAQ

Public domain CC0 1.0