Analgesics⏵
Antiandrogens⏵
Antihistamines
Azvudine
Bromhexine
Budesonide
Colchicine
Conv. Plasma
Curcumin
Famotidine
Favipiravir
Fluvoxamine
Hydroxychlor..
Ivermectin
Lifestyle⏵
Melatonin
Metformin
Minerals⏵
Molnupiravir
Monoclonals⏵
Naso/orophar..⏵
Nigella Sativa
Nitazoxanide
PPIs
Paxlovid
Quercetin
Remdesivir
Thermotherapy
Vitamins⏵
More⏵

Other
Feedback
Home
 
Top
..
Abstract
..
All quercetin studies
..
Meta analysis
..
Feedback
Home
←
next
study
→
previous
study
c19early.org COVID-19 treatment researchQuercetinQuercetin (more..)
Melatonin Meta
Metformin Meta
Antihistamines Meta
Azvudine Meta Molnupiravir Meta
Bromhexine Meta
Budesonide Meta
Colchicine Meta Nigella Sativa Meta
Conv. Plasma Meta Nitazoxanide Meta
Curcumin Meta PPIs Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Quercetin Meta
Fluvoxamine Meta Remdesivir Meta
Hydroxychlor.. Meta Thermotherapy Meta
Ivermectin Meta
Home Adoption Other Treatments
@CovidAnalysis
All Studies   Meta Analysis       

Inhibiting SARS-CoV-2 viral entry by targeting spike:ACE2 interaction with O-modified quercetin derivatives

Rosal et al., RSC Medicinal Chemistry, doi:10.1039/d4md00286e
Aug 2024  
  Post
  Facebook
Share
  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.
5,200+ studies for 112 treatments. c19early.org
In Vitro study showing that O-modified quercetin derivatives inhibit the SARS-CoV-2 spike protein:ACE2 interaction at low micromolar concentrations. Five derivatives (2e, 3a, 3b, 3c, 4b) displayed dose-dependent inhibition with IC50 values ranging from 2.22-25.70 μM, outperforming the positive control erythrosine B (IC50 = 6.16 μM). The derivatives showed low hepato-, nephro-, and cardiotoxicity and favorable physicochemical, pharmacokinetic, and drug-like properties.
Bioavailability. Quercetin has low bioavailability and studies typically use advanced formulations to improve bioavailability which may be required to reach therapeutic concentrations.
73 preclinical studies support the efficacy of quercetin for COVID-19:
45 In Silico studies1-45
22 In Vitro studies1,2,5,15,19,21,25,42,46-59
6 In Vivo animal studies5,19,52,55,60,61
In Silico studies predict inhibition of SARS-CoV-2, or minimization of side effects, with quercetin or metabolites via binding to the spikeA,2,3,9,10,22,24,25,27,30,38,39,41,42,62, MproB,2,3,7,9,11,13,15,17,18,20,23,24,27,30,34,36-38,42-45, RNA-dependent RNA polymeraseC,1-3,9,32, PLproD,3,37,45, ACE2E,22,23,27,28,37,41, TMPRSS2F,22, nucleocapsidG,3, helicaseH,3,29,34, endoribonucleaseI,39, NSP16/10J,6, cathepsin LK,26, Wnt-3L,22, FZDM,22, LRP6N,22, ezrinO,40, ADRPP,38, NRP1Q,41, EP300R,16, PTGS2S,23, HSP90AA1T,16,23, matrix metalloproteinase 9U,31, IL-6V,21,35, IL-10W,21, VEGFAX,35, and RELAY,35 proteins. In Vitro studies demonstrate inhibition of the MproB,15,46,51,59 protein, and inhibition of spike-ACE2 interactionZ,47. In Vitro studies demonstrate efficacy in Calu-3AA,50, A549AB,21, HEK293-ACE2+AC,58, Huh-7AD,25, Caco-2AE,49, Vero E6AF,19,42,49, mTECAG,52, and RAW264.7AH,52 cells. Animal studies demonstrate efficacy in K18-hACE2 miceAI,55, db/db miceAJ,52,61, BALB/c miceAK,60, and rats19. Quercetin reduced proinflammatory cytokines and protected lung and kidney tissue against LPS-induced damage in mice60, inhibits LPS-induced cytokine storm by modulating key inflammatory and antioxidant pathways in macrophages5, and inhibits SARS-CoV-2 ORF3a ion channel activity, which contributes to viral pathogenicity and cytotoxicity54.
Important missing comments or errors? Let us know.
a. The trimeric spike (S) protein is a glycoprotein that mediates viral entry by binding to the host ACE2 receptor, is critical for SARS-CoV-2's ability to infect host cells, and is a target of neutralizing antibodies. Inhibition of the spike protein prevents viral attachment, halting infection at the earliest stage.
b. The main protease or Mpro, also known as 3CLpro or nsp5, is a cysteine protease that cleaves viral polyproteins into functional units needed for replication. Inhibiting Mpro disrupts the SARS-CoV-2 lifecycle within the host cell, preventing the creation of new copies.
c. RNA-dependent RNA polymerase (RdRp), also called nsp12, is the core enzyme of the viral replicase-transcriptase complex that copies the positive-sense viral RNA genome into negative-sense templates for progeny RNA synthesis. Inhibiting RdRp blocks viral genome replication and transcription.
d. The papain-like protease (PLpro) has multiple functions including cleaving viral polyproteins and suppressing the host immune response by deubiquitination and deISGylation of host proteins. Inhibiting PLpro may block viral replication and help restore normal immune responses.
e. The angiotensin converting enzyme 2 (ACE2) protein is a host cell transmembrane protein that serves as the cellular receptor for the SARS-CoV-2 spike protein. ACE2 is expressed on many cell types, including epithelial cells in the lungs, and allows the virus to enter and infect host cells. Inhibition may affect ACE2's physiological function in blood pressure control.
f. Transmembrane protease serine 2 (TMPRSS2) is a host cell protease that primes the spike protein, facilitating cellular entry. TMPRSS2 activity helps enable cleavage of the spike protein required for membrane fusion and virus entry. Inhibition may especially protect respiratory epithelial cells, buy may have physiological effects.
g. The nucleocapsid (N) protein binds and encapsulates the viral genome by coating the viral RNA. N enables formation and release of infectious virions and plays additional roles in viral replication and pathogenesis. N is also an immunodominant antigen used in diagnostic assays.
h. The helicase, or nsp13, protein unwinds the double-stranded viral RNA, a crucial step in replication and transcription. Inhibition may prevent viral genome replication and the creation of new virus components.
i. The endoribonuclease, also known as NendoU or nsp15, cleaves specific sequences in viral RNA which may help the virus evade detection by the host immune system. Inhibition may hinder the virus's ability to mask itself from the immune system, facilitating a stronger immune response.
j. The NSP16/10 complex consists of non-structural proteins 16 and 10, forming a 2'-O-methyltransferase that modifies the viral RNA cap structure. This modification helps the virus evade host immune detection by mimicking host mRNA, making NSP16/10 a promising antiviral target.
k. Cathepsin L is a host lysosomal cysteine protease that can prime the spike protein through an alternative pathway when TMPRSS2 is unavailable. Dual targeting of cathepsin L and TMPRSS2 may maximize disruption of alternative pathways for virus entry.
l. Wingless-related integration site (Wnt) ligand 3 is a host signaling molecule that activates the Wnt signaling pathway, which is important in development, cell growth, and tissue repair. Some studies suggest that SARS-CoV-2 infection may interfere with the Wnt signaling pathway, and that Wnt3a is involved in SARS-CoV-2 entry.
m. The frizzled (FZD) receptor is a host transmembrane receptor that binds Wnt ligands, initiating the Wnt signaling cascade. FZD serves as a co-receptor, along with ACE2, in some proposed mechanisms of SARS-CoV-2 infection. The virus may take advantage of this pathway as an alternative entry route.
n. Low-density lipoprotein receptor-related protein 6 is a cell surface co-receptor essential for Wnt signaling. LRP6 acts in tandem with FZD for signal transduction and has been discussed as a potential co-receptor for SARS-CoV-2 entry.
o. The ezrin protein links the cell membrane to the cytoskeleton (the cell's internal support structure) and plays a role in cell shape, movement, adhesion, and signaling. Drugs that occupy the same spot on ezrin where the viral spike protein would bind may hindering viral attachment, and drug binding could further stabilize ezrin, strengthening its potential natural capacity to impede viral fusion and entry.
p. The Adipocyte Differentiation-Related Protein (ADRP, also known as Perilipin 2 or PLIN2) is a lipid droplet protein regulating the storage and breakdown of fats in cells. SARS-CoV-2 may hijack the lipid handling machinery of host cells and ADRP may play a role in this process. Disrupting ADRP's interaction with the virus may hinder the virus's ability to use lipids for replication and assembly.
q. Neuropilin-1 (NRP1) is a cell surface receptor with roles in blood vessel development, nerve cell guidance, and immune responses. NRP1 may function as a co-receptor for SARS-CoV-2, facilitating viral entry into cells. Blocking NRP1 may disrupt an alternative route of viral entry.
r. EP300 (E1A Binding Protein P300) is a transcriptional coactivator involved in several cellular processes, including growth, differentiation, and apoptosis, through its acetyltransferase activity that modifies histones and non-histone proteins. EP300 facilitates viral entry into cells and upregulates inflammatory cytokine production.
s. Prostaglandin G/H synthase 2 (PTGS2, also known as COX-2) is an enzyme crucial for the production of inflammatory molecules called prostaglandins. PTGS2 plays a role in the inflammatory response that can become severe in COVID-19 and inhibitors (like some NSAIDs) may have benefits in dampening harmful inflammation, but note that prostaglandins have diverse physiological functions.
t. Heat Shock Protein 90 Alpha Family Class A Member 1 (HSP90AA1) is a chaperone protein that helps other proteins fold correctly and maintains their stability. HSP90AA1 plays roles in cell signaling, survival, and immune responses. HSP90AA1 may interact with numerous viral proteins, but note that it has diverse physiological functions.
u. Matrix metalloproteinase 9 (MMP9), also called gelatinase B, is a zinc-dependent enzyme that breaks down collagen and other components of the extracellular matrix. MMP9 levels increase in severe COVID-19. Overactive MMP9 can damage lung tissue and worsen inflammation. Inhibition of MMP9 may prevent excessive tissue damage and help regulate the inflammatory response.
v. The interleukin-6 (IL-6) pro-inflammatory cytokine (signaling molecule) has a complex role in the immune response and may trigger and perpetuate inflammation. Elevated IL-6 levels are associated with severe COVID-19 cases and cytokine storm. Anti-IL-6 therapies may be beneficial in reducing excessive inflammation in severe COVID-19 cases.
w. The interleukin-10 (IL-10) anti-inflammatory cytokine helps regulate and dampen immune responses, preventing excessive inflammation. IL-10 levels can also be elevated in severe COVID-19. IL-10 could either help control harmful inflammation or potentially contribute to immune suppression.
x. Vascular Endothelial Growth Factor A (VEGFA) promotes the growth of new blood vessels (angiogenesis) and has roles in inflammation and immune responses. VEGFA may contribute to blood vessel leakiness and excessive inflammation associated with severe COVID-19.
y. RELA is a transcription factor subunit of NF-kB and is a key regulator of inflammation, driving pro-inflammatory gene expression. SARS-CoV-2 may hijack and modulate NF-kB pathways.
z. The interaction between the SARS-CoV-2 spike protein and the human ACE2 receptor is a primary method of viral entry, inhibiting this interaction can prevent the virus from attaching to and entering host cells, halting infection at an early stage.
aa. Calu-3 is a human lung adenocarcinoma cell line with moderate ACE2 and TMPRSS2 expression and SARS-CoV-2 susceptibility. It provides a model of the human respiratory epithelium, but many not be ideal for modeling early stages of infection due to the moderate expression levels of ACE2 and TMPRSS2.
ab. A549 is a human lung carcinoma cell line with low ACE2 expression and SARS-CoV-2 susceptibility. Viral entry/replication can be studied but the cells may not replicate all aspects of lung infection.
ac. HEK293-ACE2+ is a human embryonic kidney cell line engineered for high ACE2 expression and SARS-CoV-2 susceptibility.
ad. Huh-7 cells were derived from a liver tumor (hepatoma).
ae. Caco-2 cells come from a colorectal adenocarcinoma (cancer). They are valued for their ability to form a polarized cell layer with properties similar to the intestinal lining.
af. Vero E6 is an African green monkey kidney cell line with low/no ACE2 expression and high SARS-CoV-2 susceptibility. The cell line is easy to maintain and supports robust viral replication, however the monkey origin may not accurately represent human responses.
ag. mTEC is a mouse tubular epithelial cell line.
ah. RAW264.7 is a mouse macrophage cell line.
ai. A mouse model expressing the human ACE2 receptor under the control of the K18 promoter.
aj. A mouse model of obesity and severe insulin resistance leading to type 2 diabetes due to a mutation in the leptin receptor gene that impairs satiety signaling.
ak. A mouse model commonly used in infectious disease and cancer research due to higher immune response and susceptibility to infection.
Rosal et al., 16 Aug 2024, peer-reviewed, 2 authors. Contact: mcpaderes1@up.edu.ph.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperQuercetinAll
Inhibiting SARS-CoV-2 viral entry by targeting spike:ACE2 interaction with O-modified quercetin derivatives
Reuben James Z Rosal, Monissa C Paderes
RSC Medicinal Chemistry, doi:10.1039/d4md00286e
The cell entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is mediated by the interaction between the receptor-binding domain of its spike (S) protein and human angiotensinconverting enzyme 2 (ACE2). Quercetin, a flavonoid found abundantly in plants, shows potential as a SARS-CoV-2 S:ACE2 inhibitor but is known to have low bioavailability. Modification of quercetin by capping its hydroxyl moieties could enhance the metabolic stability, solubility, and bioavailability, and reduce toxicity. In this study, sixteen ( 16 ) O-modified quercetin derivatives were synthesized by incorporating alkyl and acyl moieties of varying lengths, sizes, and polarities to the hydroxyl groups. The SARS-CoV-2 S:ACE2 inhibitory activity and toxicity of the synthesized derivatives were assessed in vitro, and their physicochemical properties, pharmacokinetics, and drug-likeness were predicted and evaluated using the SwissADME web tool. Results showed that functionalization of the hydroxyl moieties of quercetin generally resulted in more potent inhibitors (>50% inhibition). Five (5) derivatives displayed a dose-dependent inhibition against the SARS-CoV-2 S:ACE2 interaction with promising IC 50 values (i.e., 2e (IC 50 = 7.52 μM), 3a (IC 50 = 5.00 μM), 3b (IC 50 = 25.70 μM), 3c (IC 50 = 2.22 μM), and 4b (IC 50 = 3.28 μM)). Moreover, these compounds exhibited low hepato-, nephro-, and cardiotoxicity, and their SwissADME profiles indicated favorable physicochemical, pharmacokinetic, and drug-like properties, suggesting their potential as promising lead SARS-CoV-2 S:ACE2 inhibitors.
Author contributions Synthesis and characterization, methodology, investigation, and formal analysis, R. J. Z. R.; writingoriginal draft, review, and editing, R. J. Z. R. and M. C. P.; conceptualization, validation, funding acquisition, supervision, and project administration, M. C. P. Conflicts of interest The authors declare no conflict of interest.
References
Al-Jabban, Zhang, Guanglin, Mekuria, Harinantenaina et al., None, Nat. Prod. Commun
Almeida, Borge, Piskula, Tudose, Tudoreanu et al., None, Compr. Rev. Food Sci. Food Saf
Antonio, Wiedemann, Veiga-Junior, None, RSC Adv
Baell, Nissink, None, ACS Chem. Biol
Bojadzic, Alcazar, Chen, Chuang, Condor Capcha et al., None, ACS Infect. Dis
Brenk, Schipani, James, Krasowski, Gilbert et al., None, ChemMedChem
Cao, Jing, Wu, Shi, None, Int. J. Food Sci. Nutr
Carino, Moraca, Fiorillo, Marchianò, Sepe et al., None, Front. Chem
Cui, Yang, Yang, None, Front. Mol. Biosci
Daina, Michielin, Zoete, None, Sci. Rep
Danihelová, Viskupičová, Šturdík, None, Acta Chim. Slov
Dong, Galvan Achi, Du, Rong, Cui, None, Cell Insight
Francisco, Paderes, None, ACS Omega
Geldenhuys, Mohammad, Adkins, Lockman, None, Ther. Delivery
Guan, Yang, Cai, Sun, Di et al., None, MedChemComm
Hasnat, Shompa, Islam, Alam, Richi et al., None, Heliyon
Hernandez, Genio, Casanova, Conato, Paderes, None, ChemistryOpen
Li, None, Annu. Rev. Virol
Li, Yao, Han, Yang, Chaudhry et al., None, Nutrients
Lin, Will, None, Toxicol. Sci
Lipinski, Lombardo, Dominy, Feeney, None, Adv. Drug Delivery Rev
Lipinski, Lombardo, Dominy, Feeney, None, Adv. Drug Delivery Rev
Lipinski, None, J. Pharmacol. Toxicol. Methods
Ma, -M. Liu, -M. Liu, -Y. Yuan, Xu et al., None, Eur. J. Med. Chem
Mani, Johnson, Steel, Broszczak, Neilsen et al., None, Virus Res
Martin, None, J. Med. Chem
Mattarei, Biasutto, Rastrelli, Garbisa, Marotta et al., None, Molecules
Meanwell, None, Chem. Res. Toxicol
Mouffouk, Mouffouk, Mouffouk, Hambaba, Haba, None, Eur. J. Pharmacol
Muchtaridi, Fauzi, Khairul Ikram, Mohd, Gazzali et al., None, Molecules
Ni, Yang, Yang, Bao, Li et al., None, Crit. Care
Pan, Fang, Zhang, Pan, Liu et al., None, Comput. Struct. Biotechnol. J
Perlman, Netland, None, Nat. Rev. Microbiol
Prachayasittikul, Prachayasittikul, None, EXCLI J
Rao, Owoyale, None, J. Heterocyclic Chem
Shang, Wan, Luo, Ye, Geng et al., None, Proc. Natl. Acad. Sci. U. S. A
Sohrabi, Alsafi, O'neill, Khan, Kerwan et al., None, Int. J. Surg
Sopjani, Falco, Impellitteri, Guarrasi, Nguyen Thi et al., None, Phytother. Res
Stretch, /z) calculated for
Stretch, CO stretch), 1585 (aromatic C-C stretch), 1321 (C-O stretch). HRMS-ESI + (m/z) calculated for
Stretch, CO stretch), 1587 (aromatic C-C stretch), 1275 (C-O stretch). HRMS-ESI + (m/z) calculated for
Stretch, CO stretch), 1587 (aromatic C-C stretch), 1277 (C-O stretch). HRMS-ESI + (m/z) calculated for
Stretch, CO stretch), 1589 (aromatic C-C stretch), 1277 (C-O stretch). HRMS-ESI + (m/z) calculated for
Stretch, CO stretch), 1597 (aromatic C-C stretch), 1279 (C-O stretch), 1225 (C-F stretch)
Stretch, HRMS-ESI + (m/z) calculated for
Stretch, HRMS-ESI + (m/z) calculated for
Stretch, None
Stretch, None
Stretch, None
Stretch, None
Stretch, None
Stretch, None
Stretch, None
Stretch, None
Szabó, Crowe, Mamotte, Strappe, None, Front. Cell. Infect. Microbiol
Thilakarathna, Rupasinghe, None, Nutrients
Toor, Banerjee, Lipsa Rath, Darji, None, Eur. J. Pharmacol
Tzvetkov, Kirilov, Matin, Atanasov, None, Nephrol., Dial., Transplant
Veber, Johnson, Cheng, Smith, Ward et al., None, J. Med. Chem
Walle, None, Mol. Pharmaceutics
Williamson, Kerimi, None, Biochem. Pharmacol
Ye, Luo, Ye, She, Sun et al., None, Phytomedicine
Zhang, -L. Wu, Zhang, Deng, Peng, None, J. Integr. Med
Zhang, None, ACS Omega
Zhang, Wang, Yang, Zhou, Zhang, None, PLoS One
Zhou, Yang, Wang, Hu, Zhang et al., None, Nature
{ 'indexed': {'date-parts': [[2024, 9, 20]], 'date-time': '2024-09-20T04:19:46Z', 'timestamp': 1726805986178}, 'reference-count': 51, 'publisher': 'Royal Society of Chemistry (RSC)', 'issue': '9', 'license': [ { 'start': { 'date-parts': [[2025, 8, 16]], 'date-time': '2025-08-16T00:00:00Z', 'timestamp': 1755302400000}, 'content-version': 'am', 'delay-in-days': 593, 'URL': 'http://rsc.li/journals-terms-of-use'}], 'funder': [ { 'DOI': '10.13039/501100011096', 'name': 'Philippine Council for Health Research and Development', 'doi-asserted-by': 'publisher', 'id': [{'id': '10.13039/501100011096', 'id-type': 'DOI', 'asserted-by': 'publisher'}]}, { 'DOI': '10.13039/501100010892', 'name': 'Department of Science and Technology, Republic of the Philippines', 'doi-asserted-by': 'publisher', 'id': [{'id': '10.13039/501100010892', 'id-type': 'DOI', 'asserted-by': 'publisher'}]}], 'content-domain': {'domain': ['rsc.org'], 'crossmark-restriction': True}, 'abstract': '<jats:p>\n' ' <jats:italic>O</jats:italic>-Alkylated and acylated quercetin derivatives were ' 'found to inhibit SARS-CoV-2 S:ACE2 interaction <jats:italic>in vitro</jats:italic> and ' 'exhibited low hepato-, nephro-, and cardiotoxicity.</jats:p>', 'DOI': '10.1039/d4md00286e', 'type': 'journal-article', 'created': {'date-parts': [[2024, 8, 16]], 'date-time': '2024-08-16T14:57:45Z', 'timestamp': 1723820265000}, 'page': '3212-3222', 'update-policy': 'http://dx.doi.org/10.1039/rsc_crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Inhibiting SARS-CoV-2 viral entry by targeting spike:ACE2 interaction with <i>O</i>-modified ' 'quercetin derivatives', 'prefix': '10.1039', 'volume': '15', 'author': [ { 'ORCID': 'http://orcid.org/0009-0008-4028-9917', 'authenticated-orcid': False, 'given': 'Reuben James Z.', 'family': 'Rosal', 'sequence': 'first', 'affiliation': [ { 'name': 'Institute of Chemistry, College of Science, University of the ' 'Philippines Diliman, Quezon City 1101, Philippines'}]}, { 'ORCID': 'http://orcid.org/0000-0002-4042-4153', 'authenticated-orcid': False, 'given': 'Monissa C.', 'family': 'Paderes', 'sequence': 'additional', 'affiliation': [ { 'name': 'Institute of Chemistry, College of Science, University of the ' 'Philippines Diliman, Quezon City 1101, Philippines'}]}], 'member': '292', 'published-online': {'date-parts': [[2024]]}, 'reference': [ { 'key': 'D4MD00286E/cit1/1', 'doi-asserted-by': 'crossref', 'first-page': '71', 'DOI': '10.1016/j.ijsu.2020.02.034', 'volume': '76', 'author': 'Sohrabi', 'year': '2020', 'journal-title': 'Int. J. Surg.'}, { 'key': 'D4MD00286E/cit2/1', 'doi-asserted-by': 'crossref', 'first-page': '616341', 'DOI': '10.3389/fmolb.2020.616341', 'volume': '7', 'author': 'Cui', 'year': '2020', 'journal-title': 'Front. Mol. Biosci.'}, { 'key': 'D4MD00286E/cit3/1', 'doi-asserted-by': 'crossref', 'first-page': '270', 'DOI': '10.1038/s41586-020-2012-7', 'volume': '579', 'author': 'Zhou', 'year': '2020', 'journal-title': 'Nature'}, { 'key': 'D4MD00286E/cit4/1', 'unstructured': 'WHO Coronavirus (COVID-19) Dashboard, https://covid19.who.int , ' '(accessed 2024-03-04)'}, { 'key': 'D4MD00286E/cit5/1', 'doi-asserted-by': 'crossref', 'first-page': '237', 'DOI': '10.1146/annurev-virology-110615-042301', 'volume': '3', 'author': 'Li', 'year': '2016', 'journal-title': 'Annu. Rev. Virol.'}, { 'key': 'D4MD00286E/cit6/1', 'doi-asserted-by': 'crossref', 'first-page': '439', 'DOI': '10.1038/nrmicro2147', 'volume': '7', 'author': 'Perlman', 'year': '2009', 'journal-title': 'Nat. Rev. Microbiol.'}, { 'key': 'D4MD00286E/cit7/1', 'doi-asserted-by': 'crossref', 'first-page': '11727', 'DOI': '10.1073/pnas.2003138117', 'volume': '117', 'author': 'Shang', 'year': '2020', 'journal-title': 'Proc. Natl. Acad. Sci. U. S. A.'}, { 'key': 'D4MD00286E/cit8/1', 'doi-asserted-by': 'crossref', 'first-page': '422', 'DOI': '10.1186/s13054-020-03120-0', 'volume': '24', 'author': 'Ni', 'year': '2020', 'journal-title': 'Crit. Care'}, { 'key': 'D4MD00286E/cit9/1', 'doi-asserted-by': 'crossref', 'first-page': '375', 'DOI': '10.1093/ndt/gfad208', 'volume': '39', 'author': 'Tzvetkov', 'year': '2023', 'journal-title': 'Nephrol., Dial., Transplant.'}, { 'key': 'D4MD00286E/cit10/1', 'doi-asserted-by': 'crossref', 'first-page': 'e27533', 'DOI': '10.1016/j.heliyon.2024.e27533', 'volume': '10', 'author': 'Hasnat', 'year': '2024', 'journal-title': 'Heliyon'}, { 'key': 'D4MD00286E/cit11/1', 'doi-asserted-by': 'crossref', 'first-page': '43109', 'DOI': '10.1021/acsomega.3c06619', 'volume': '8', 'author': 'Francisco', 'year': '2023', 'journal-title': 'ACS Omega'}, { 'key': 'D4MD00286E/cit12/1', 'doi-asserted-by': 'crossref', 'first-page': 'e202300087', 'DOI': '10.1002/open.202300087', 'volume': '13', 'author': 'Hernandez', 'year': '2024', 'journal-title': 'ChemistryOpen'}, { 'key': 'D4MD00286E/cit13/1', 'doi-asserted-by': 'crossref', 'first-page': '1353971', 'DOI': '10.3389/fcimb.2024.1353971', 'volume': '14', 'author': 'Szabó', 'year': '2024', 'journal-title': 'Front. Cell. Infect. Microbiol.'}, { 'key': 'D4MD00286E/cit14/1', 'doi-asserted-by': 'crossref', 'first-page': '167', 'DOI': '10.3390/nu8030167', 'volume': '8', 'author': 'Li', 'year': '2016', 'journal-title': 'Nutrients'}, { 'key': 'D4MD00286E/cit15/1', 'doi-asserted-by': 'crossref', 'first-page': '197989', 'DOI': '10.1016/j.virusres.2020.197989', 'volume': '284', 'author': 'Mani', 'year': '2020', 'journal-title': 'Virus Res.'}, { 'key': 'D4MD00286E/cit16/1', 'doi-asserted-by': 'crossref', 'first-page': '152', 'DOI': '10.1016/j.joim.2020.02.005', 'volume': '18', 'author': 'Zhang', 'year': '2020', 'journal-title': 'J. Integr. Med.'}, { 'key': 'D4MD00286E/cit17/1', 'doi-asserted-by': 'crossref', 'first-page': '1589', 'DOI': '10.1002/ptr.8123', 'volume': '38', 'author': 'Sopjani', 'year': '2024', 'journal-title': 'Phytother. Res.'}, { 'key': 'D4MD00286E/cit18/1', 'doi-asserted-by': 'crossref', 'first-page': '114123', 'DOI': '10.1016/j.bcp.2020.114123', 'volume': '178', 'author': 'Williamson', 'year': '2020', 'journal-title': 'Biochem. Pharmacol.'}, { 'key': 'D4MD00286E/cit19/1', 'doi-asserted-by': 'crossref', 'first-page': '3980', 'DOI': '10.3390/molecules25173980', 'volume': '25', 'author': 'Muchtaridi', 'year': '2020', 'journal-title': 'Molecules'}, { 'key': 'D4MD00286E/cit20/1', 'doi-asserted-by': 'crossref', 'first-page': '23379', 'DOI': '10.1039/D0RA03774E', 'volume': '10', 'author': 'Antonio', 'year': '2020', 'journal-title': 'RSC Adv.'}, { 'key': 'D4MD00286E/cit21/1', 'doi-asserted-by': 'crossref', 'first-page': '173759', 'DOI': '10.1016/j.ejphar.2020.173759', 'volume': '891', 'author': 'Mouffouk', 'year': '2021', 'journal-title': 'Eur. J. Pharmacol.'}, { 'key': 'D4MD00286E/cit22/1', 'doi-asserted-by': 'crossref', 'first-page': '100144', 'DOI': '10.1016/j.cellin.2023.100144', 'volume': '3', 'author': 'Dong', 'year': '2024', 'journal-title': 'Cell Insight'}, { 'key': 'D4MD00286E/cit23/1', 'doi-asserted-by': 'crossref', 'first-page': '113857', 'DOI': '10.1016/j.ejmech.2021.113857', 'volume': '226', 'author': 'Ma', 'year': '2021', 'journal-title': 'Eur. J. Med. Chem.'}, { 'key': 'D4MD00286E/cit24/1', 'doi-asserted-by': 'crossref', 'first-page': '153401', 'DOI': '10.1016/j.phymed.2020.153401', 'volume': '85', 'author': 'Ye', 'year': '2021', 'journal-title': 'Phytomedicine'}, { 'key': 'D4MD00286E/cit25/1', 'doi-asserted-by': 'crossref', 'first-page': '3518', 'DOI': '10.1016/j.csbj.2020.11.010', 'volume': '18', 'author': 'Pan', 'year': '2020', 'journal-title': 'Comput. Struct. Biotechnol. J.'}, { 'key': 'D4MD00286E/cit26/1', 'doi-asserted-by': 'crossref', 'first-page': '714', 'DOI': '10.1111/1541-4337.12342', 'volume': '17', 'author': 'Almeida', 'year': '2018', 'journal-title': 'Compr. Rev. Food Sci. Food Saf.'}, { 'key': 'D4MD00286E/cit27/1', 'doi-asserted-by': 'crossref', 'first-page': '3367', 'DOI': '10.3390/nu5093367', 'volume': '5', 'author': 'Thilakarathna', 'year': '2013', 'journal-title': 'Nutrients'}, { 'key': 'D4MD00286E/cit28/1', 'doi-asserted-by': 'crossref', 'first-page': '826', 'DOI': '10.1021/mp700071d', 'volume': '4', 'author': 'Walle', 'year': '2007', 'journal-title': 'Mol. Pharmaceutics'}, { 'key': 'D4MD00286E/cit29/1', 'doi-asserted-by': 'crossref', 'first-page': '59', 'DOI': '10.2478/v10188-012-0010-6', 'volume': '5', 'author': 'Danihelová', 'year': '2012', 'journal-title': 'Acta Chim. Slov.'}, { 'key': 'D4MD00286E/cit30/1', 'first-page': '2113', 'volume': '10', 'author': 'Al-Jabban', 'year': '2015', 'journal-title': 'Nat. Prod. Commun.'}, { 'key': 'D4MD00286E/cit31/1', 'doi-asserted-by': 'crossref', 'first-page': '4722', 'DOI': '10.3390/molecules15074722', 'volume': '15', 'author': 'Mattarei', 'year': '2010', 'journal-title': 'Molecules'}, { 'key': 'D4MD00286E/cit32/1', 'doi-asserted-by': 'crossref', 'first-page': '1293', 'DOI': '10.1002/jhet.5570130629', 'volume': '13', 'author': 'Rao', 'year': '1976', 'journal-title': 'J. Heterocyclic Chem.'}, { 'key': 'D4MD00286E/cit33/1', 'doi-asserted-by': 'crossref', 'first-page': 'e105725', 'DOI': '10.1371/journal.pone.0105725', 'volume': '9', 'author': 'Zhang', 'year': '2014', 'journal-title': 'PLoS One'}, { 'key': 'D4MD00286E/cit34/1', 'doi-asserted-by': 'crossref', 'first-page': '572885', 'DOI': '10.3389/fchem.2020.572885', 'volume': '8', 'author': 'Carino', 'year': '2020', 'journal-title': 'Front. Chem.'}, { 'key': 'D4MD00286E/cit35/1', 'doi-asserted-by': 'crossref', 'first-page': '1519', 'DOI': '10.1021/acsinfecdis.1c00070', 'volume': '7', 'author': 'Bojadzic', 'year': '2021', 'journal-title': 'ACS Infect. Dis.'}, { 'key': 'D4MD00286E/cit36/1', 'doi-asserted-by': 'crossref', 'first-page': '173720', 'DOI': '10.1016/j.ejphar.2020.173720', 'volume': '890', 'author': 'Toor', 'year': '2021', 'journal-title': 'Eur. J. Pharmacol.'}, { 'key': 'D4MD00286E/cit37/1', 'doi-asserted-by': 'crossref', 'first-page': '18206', 'DOI': '10.1021/acsomega.2c01121', 'volume': '7', 'author': 'Zhang', 'year': '2022', 'journal-title': 'ACS Omega'}, { 'key': 'D4MD00286E/cit38/1', 'doi-asserted-by': 'crossref', 'first-page': '114', 'DOI': '10.1093/toxsci/kfr339', 'volume': '126', 'author': 'Lin', 'year': '2011', 'journal-title': 'Toxicol. Sci.'}, { 'key': 'D4MD00286E/cit39/1', 'doi-asserted-by': 'crossref', 'first-page': '42717', 'DOI': '10.1038/srep42717', 'volume': '7', 'author': 'Daina', 'year': '2017', 'journal-title': 'Sci. Rep.'}, { 'key': 'D4MD00286E/cit40/1', 'doi-asserted-by': 'crossref', 'first-page': '3', 'DOI': '10.1016/S0169-409X(00)00129-0', 'volume': '46', 'author': 'Lipinski', 'year': '2001', 'journal-title': 'Adv. Drug Delivery Rev.'}, { 'key': 'D4MD00286E/cit41/1', 'doi-asserted-by': 'crossref', 'first-page': '235', 'DOI': '10.1016/S1056-8719(00)00107-6', 'volume': '44', 'author': 'Lipinski', 'year': '2000', 'journal-title': 'J. Pharmacol. Toxicol. Methods'}, { 'key': 'D4MD00286E/cit42/1', 'doi-asserted-by': 'crossref', 'first-page': '1420', 'DOI': '10.1021/tx200211v', 'volume': '24', 'author': 'Meanwell', 'year': '2011', 'journal-title': 'Chem. Res. Toxicol.'}, { 'key': 'D4MD00286E/cit43/1', 'doi-asserted-by': 'crossref', 'first-page': '2615', 'DOI': '10.1021/jm020017n', 'volume': '45', 'author': 'Veber', 'year': '2002', 'journal-title': 'J. Med. Chem.'}, { 'key': 'D4MD00286E/cit44/1', 'doi-asserted-by': 'crossref', 'first-page': '148', 'DOI': '10.1039/C8MD00472B', 'volume': '10', 'author': 'Guan', 'year': '2019', 'journal-title': 'MedChemComm'}, { 'key': 'D4MD00286E/cit45/1', 'doi-asserted-by': 'crossref', 'first-page': '437', 'DOI': '10.3109/09637486.2012.759186', 'volume': '64', 'author': 'Cao', 'year': '2013', 'journal-title': 'Int. J. Food Sci. Nutr.'}, { 'key': 'D4MD00286E/cit46/1', 'first-page': '113', 'volume': '15', 'author': 'Prachayasittikul', 'year': '2016', 'journal-title': 'EXCLI J.'}, { 'key': 'D4MD00286E/cit47/1', 'doi-asserted-by': 'crossref', 'first-page': '961', 'DOI': '10.4155/tde.15.32', 'volume': '6', 'author': 'Geldenhuys', 'year': '2015', 'journal-title': 'Ther. Delivery'}, { 'key': 'D4MD00286E/cit48/1', 'doi-asserted-by': 'crossref', 'first-page': '3', 'DOI': '10.1016/S0169-409X(00)00129-0', 'volume': '46', 'author': 'Lipinski', 'year': '2001', 'journal-title': 'Adv. Drug Delivery Rev.'}, { 'key': 'D4MD00286E/cit49/1', 'doi-asserted-by': 'crossref', 'first-page': '3164', 'DOI': '10.1021/jm0492002', 'volume': '48', 'author': 'Martin', 'year': '2005', 'journal-title': 'J. Med. Chem.'}, { 'key': 'D4MD00286E/cit50/1', 'doi-asserted-by': 'crossref', 'first-page': '36', 'DOI': '10.1021/acschembio.7b00903', 'volume': '13', 'author': 'Baell', 'year': '2018', 'journal-title': 'ACS Chem. Biol.'}, { 'key': 'D4MD00286E/cit51/1', 'doi-asserted-by': 'crossref', 'first-page': '435', 'DOI': '10.1002/cmdc.200700139', 'volume': '3', 'author': 'Brenk', 'year': '2008', 'journal-title': 'ChemMedChem'}], 'container-title': 'RSC Medicinal Chemistry', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'http://pubs.rsc.org/en/content/articlepdf/2024/MD/D4MD00286E', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2024, 9, 19]], 'date-time': '2024-09-19T11:14:05Z', 'timestamp': 1726744445000}, 'score': 1, 'resource': {'primary': {'URL': 'https://xlink.rsc.org/?DOI=D4MD00286E'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2024]]}, 'references-count': 51, 'journal-issue': {'issue': '9', 'published-print': {'date-parts': [[2024, 9, 19]]}}, 'URL': 'http://dx.doi.org/10.1039/d4md00286e', 'relation': {}, 'ISSN': ['2632-8682'], 'subject': [], 'container-title-short': 'RSC Med. Chem.', 'published': {'date-parts': [[2024]]}}
Loading..
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.
  or use drag and drop   
Submit    
Post
Share
@CovidAnalysis
FAQ
Public domain CC0 1.0