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

Other
Feedback
Home
Top
Abstract
All ivermectin studies
Meta analysis
 
Feedback
Home
next
study
previous
study
c19ivm.org COVID-19 treatment researchIvermectinIvermectin (more..)
Melatonin Meta
Metformin Meta
Azvudine Meta
Bromhexine Meta Molnupiravir Meta
Budesonide Meta
Colchicine Meta
Conv. Plasma Meta Nigella Sativa Meta
Curcumin Meta Nitazoxanide Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Quercetin Meta
Fluvoxamine Meta Remdesivir Meta
Hydroxychlor.. Meta Thermotherapy Meta
Ivermectin Meta

All Studies   Meta Analysis    Recent:   

Microfluidic Diffusion Sizing Applied to the Study of Natural Products and Extracts That Modulate the SARS-CoV-2 Spike RBD/ACE2 Interaction

Fauquet et al., Molecules, doi:10.3390/molecules28248072
Dec 2023  
  Post
  Facebook
Share
  Source   PDF   All Studies   Meta AnalysisMeta
Ivermectin for COVID-19
4th treatment shown to reduce risk in August 2020
 
*, now with p < 0.00000000001 from 104 studies, recognized in 22 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,300+ studies for 75 treatments. c19ivm.org
In Vitro study showing that ivermectin modulated SARS-CoV-2 spike RBD-ACE2 interaction, suggesting efficacy for COVID-19, at a concentration of 1nM, well below concentrations achieved in practice. Authors use microfluidic diffusional sizing to measure changes in hydrodynamic radius. Promising results were also seen for naringenin and extracts of Rhei radix and Chenopodium quinoa.
68 preclinical studies support the efficacy of ivermectin for COVID-19:
Ivermectin, better known for antiparasitic activity, is a broad spectrum antiviral with activity against many viruses including H7N766, Dengue32,67,68, HIV-168, Simian virus 4069, Zika32,70,71, West Nile71, Yellow Fever72,73, Japanese encephalitis72, Chikungunya73, Semliki Forest virus73, Human papillomavirus52, Epstein-Barr52, BK Polyomavirus74, and Sindbis virus73.
Ivermectin inhibits importin-α/β-dependent nuclear import of viral proteins66,68,69,75, shows spike-ACE2 disruption at 1nM with microfluidic diffusional sizing33, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination36,76, shows dose-dependent inhibition of wildtype and omicron variants31, exhibits dose-dependent inhibition of lung injury56,61, may inhibit SARS-CoV-2 via IMPase inhibition32, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation5, inhibits SARS-CoV-2 3CLpro49, may inhibit SARS-CoV-2 RdRp activity24, may minimize viral myocarditis by inhibiting NF-κB/p65-mediated inflammation in macrophages55, may be beneficial for COVID-19 ARDS by blocking GSDMD and NET formation77, shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model sharing key pathological features of severe COVID-1954,78, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage4, may minimize SARS-CoV-2 induced cardiac damage35,43, increases Bifidobacteria which play a key role in the immune system79, has immunomodulatory46 and anti-inflammatory65,80 properties, and has an extensive and very positive safety profile81.
Fauquet et al., 13 Dec 2023, peer-reviewed, 5 authors. Contact: julie.carette@umons.ac.be (corresponding author), jason.fauquet@umons.ac.be, pierre.duez@umons.ac.be, amandine.nachtergael@umons.ac.be, zjl_ljz@mail.hzau.edu.cn.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperIvermectinAll
Microfluidic Diffusion Sizing Applied to the Study of Natural Products and Extracts That Modulate the SARS-CoV-2 Spike RBD/ACE2 Interaction
Jason Fauquet, Julie Carette, Pierre Duez, Jiuliang Zhang, Amandine Nachtergael
Molecules, doi:10.3390/molecules28248072
The interaction between SARS-CoV-2 spike RBD and ACE2 proteins is a crucial step for host cell infection by the virus. Without it, the entire virion entrance mechanism is compromised. The aim of this study was to evaluate the capacity of various natural product classes, including flavonoids, anthraquinones, saponins, ivermectin, chloroquine, and erythromycin, to modulate this interaction. To accomplish this, we applied a recently developed a microfluidic diffusional sizing (MDS) technique that allows us to probe protein-protein interactions via measurements of the hydrodynamic radius (R h ) and dissociation constant (K D ); the evolution of R h is monitored in the presence of increasing concentrations of the partner protein (ACE2); and the K D is determined through a binding curve experimental design. In a second time, with the protein partners present in equimolar amounts, the R h of the protein complex was measured in the presence of different natural products. Five of the nine natural products/extracts tested were found to modulate the formation of the protein complex. A methanol extract of Chenopodium quinoa Willd bitter seed husks (50 µg/mL; bisdesmoside saponins) and the flavonoid naringenin (1 µM) were particularly effective. This rapid selection of effective modulators will allow us to better understand agents that may prevent SARS-CoV-2 infection.
Author Contributions: Conceptualization, P.D. and A.N.; methodology, J.F.; investigation, J.F. and J.C.; resources, Laboratory of Pharmacognosy and Therapeutic chemistry form UMONS; data curation, J.F.; Visualization, J.Z., writing-original draft preparation, J.C.; writing-review and editing, J.C., A.N., J.F. and P.D. All authors have read and agreed to the published version of the manuscript. Funding: This work was partly supported by Wallonie-Bruxelles International through the project Wallonie-Bruxelles/China (MOST) "Anti-inflammatory herbal medicines and their active components to fight the cytokine storm associated with COVID-19 diseases (TCM-Cyt)". This work was supported by the Fonds pour la Recherche Scientifique FNRS under grant N • CDR J.0058.21 "PlasmLip", which contributed to the acquisition of the fluidity instrument. Veronica Taco is warmly thanked for her analysis of the Chenopodium quinoa husk extract and for giving us access to this sample; Veronica Taco is a scholarship holder from the Académie de Recherche et d'Enseignement Supérieur (ARES, Belgium). This work was also supported by the National Key R&D Program of China, 2021YFE0194000. Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable. Conflicts of Interest: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the..
References
Abdelli, Hassani, Bekkel Brikci, Ghalem, In Silico study the inhibition of angiotensin converting enzyme 2 receptor of COVID-19 by Ammoides verticillata components harvested from Western Algeria, J. Biomol. Struct. Dyn, doi:10.1080/07391102.2020.1763199
Allen, Watanabe, Chawla, Newby, Crispin, Subtle Influence of ACE2 Glycan Processing on SARS-CoV-2 Recognition, J. Mol. Biol, doi:10.1016/j.jmb.2020.166762
Alqathama, Ahmad, Alsaedi, Alghamdi, Abkar et al., The vital role of animal, marine, and microbial natural products against COVID-19, Pharm. Biol, doi:10.1080/13880209.2022.2039215
Anwar, Altayb, Al-Abbasi, Kumar, Kamal, The computational intervention of macrolide antibiotics in the treatment of COVID-19, Curr. Pharm. Des, doi:10.2174/1381612827666210125121954
Arosio, Müller, Rajah, Yates, Aprile et al., Microfluidic diffusion analysis of the sizes and interactions of proteins under native solution conditions, ACS Nano, doi:10.1021/acsnano.5b04713
Badraoui, Saoudi, Hamadou, Elkahoui, Siddiqui et al., Antiviral effects of artemisinin and Its derivatives against SARS-CoV-2 main protease: Computational evidences and interactions with ACE2 allelic variants, Pharmaceuticals, doi:10.3390/ph15020129
Balkrishna, Pokhrel, Singh, Joshi, Mulay et al., Withanone from Withania somnifera attenuates SARS-CoV-2 RBD and host ACE2 interactions to rescue spike protein induced pathologies in humanized zebrafish model, Drug Des. Devel. Ther, doi:10.2147/DDDT.S292805
Barton, Macgowan, Kutuzov, Dushek, Barton et al., Effects of common mutations in the SARS-CoV-2 Spike RBD and its ligand, the human ACE2 receptor on binding affinity and kinetics, eLife, doi:10.7554/eLife.70658
Basu, Sarkar, Maulik, Molecular docking study of potential phytochemicals and their effects on the complex of SARS-CoV2 spike protein and human ACE2, Sci. Rep, doi:10.1038/s41598-020-74715-4
Bhakti, Insuffisance Respiratoire Hypoxémique Aigüe (Syndrome de Détresse Respiratoire Aiguë [SDRA, N. Engl. J. Med, doi:10.1056/NEJMoa062200
Biber, Harmelin, Lev, Ram, Shaham et al., The effect of ivermectin on the viral load and culture viability in early treatment of nonhospitalized patients with mild COVID-19-A double-blind, randomized placebo-controlled trial, Int. J. Infect. Dis, doi:10.1016/j.ijid.2022.07.003
Braz, Silveira, Marinho, De Moraes, Moraes Filho et al., In Silico study of azithromycin, chloroquine and hydroxychloroquine and their potential mechanisms of action against SARS-CoV-2 infection, Int. J. Antimicrob. Agents, doi:10.1016/j.ijantimicag.2020.106119
Cai, Zhang, Xiao, Peng, Sterling et al., Distinct conformational states of SARS-CoV-2 spike protein, Science, doi:10.1126/science.abd4251
Caly, Druce, Catton, Jans, Wagstaff, The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro, Antivir. Res, doi:10.1016/j.antiviral.2020.104787
Camargo, Vuille-Dit-Bille, Meier, Verrey, ACE2 and gut amino acid transport, Clin. Sci, doi:10.1042/CS20200477
Caohuy, Eidelman, Chen, Liu, Yang et al., Common cardiac medications potently inhibit ACE2 binding to the SARS-CoV-2 Spike, and block virus penetration and infectivity in human lung cells, Sci. Rep, doi:10.1038/s41598-021-01690-9
Charles, Nachtergael, Ouedraogo, Belayew, Duez, Effects of chemopreventive natural products on nonhomologous end-joining DNA double-strand break repair, Mutat. Res./Genet. Toxicol. Environ. Mutagen, doi:10.1016/j.mrgentox.2014.04.014
Chen, Chan, Jiang, Kao, Lu et al., In Vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds, J. Clin. Virol, doi:10.1016/j.jcv.2004.03.003
Chen, Du, Potential Natural Compounds for Preventing SARS-CoV-2 (2019-nCoV) Infection, doi:10.20944/preprints202001.0358.v3
Chen, Liu, Gao, Chen, Vong et al., Astragali Radix (Huangqi): A promising edible immunomodulatory herbal medicine, J. Ethnopharmacol, doi:10.1016/j.jep.2020.112895
Chen, Yang, Hamdoun, Chung, Lam et al., 1,2,3,4,6-Pentagalloyl Glucose, a RBD-ACE2 Binding Inhibitor to Prevent SARS-CoV-2 Infection, Front. Pharmacol, doi:10.3389/fphar.2021.634176
Cheng, Ng, Chiang, Lin, Antiviral effects of saikosaponins on human coronavirus 229E in vitro, Clin. Exp. Pharmacol. Physiol, doi:10.1111/j.1440-1681.2006.04415.x
Chitsike, Krstenansky, Duerksen-Hughes, ACE2: S1 RBD interaction-targeted peptides and small molecules as potential COVID-19 therapeutics, Adv. Pharmacol. Pharm. Sci, doi:10.1155/2021/1828792
Cinatl, Morgenstern, Bauer, Chandra, Rabenau et al., an active component of liquorice roots, and replication of SARS-associated coronavirus, Lancet, doi:10.1016/S0140-6736(03)13615-X
Clementi, Scagnolari, D'amore, Palombi, Criscuolo et al., Naringenin is a powerful inhibitor of SARS-CoV-2 infection in vitro, Pharmacol. Res, doi:10.1016/j.phrs.2020.105255
Du, Zhu, Chen, Zhou, Yang et al., Revealing the therapeutic targets and molecular mechanisms of emodin-treated coronavirus disease 2019 via a systematic study of network pharmacology, Aging, doi:10.18632/aging.203098
Ema, Assessment Report on Rheum palmatum L. and Rheum Officinale Baillon, Radix; HMPC-European Medicines Agency
Falade, Adelusi, Adedotun, Abdul-Hammed, Lawal et al., In Silico investigation of saponins and tannins as potential inhibitors of SARS-CoV-2 main protease (M pro ), Silico Pharmacol, doi:10.1007/s40203-020-00071-w
Fiedler, Piziorska, Denninger, Morgunov, Ilsley et al., Antibody Affinity Governs the Inhibition of SARS-CoV-2 Spike/ACE2 Binding in Patient Serum, ACS Infect. Dis, doi:10.1021/acsinfecdis.1c00047
Frediansyah, Sofyantoro, Alhumaid, Al Mutair, Albayat et al., Microbial natural products with antiviral activities, including anti-SARS-CoV-2: A review, Molecules, doi:10.3390/molecules27134305
Gangadevi, Badavath, Thakur, Yin, De Jonghe et al., Kobophenol A Inhibits Binding of Host ACE2 Receptor with Spike RBD Domain of SARS-CoV-2, a Lead Compound for Blocking COVID-19, J. Phys. Chem. Lett, doi:10.1021/acs.jpclett.0c03119
Goel, Jain, Kumari, The role of ACE2 receptor and its age related immunity in COVID-19, Int. J. Pharm. Sci. Rev. Res
González Canga, Sahagún Prieto, Diez Liébana, Fernández Martínez, Sierra et al., The pharmacokinetics and interactions of ivermectin in humans-A mini-review, AAPS J, doi:10.1208/s12248-007-9000-9
Goswami, Bagchi, Molecular Docking study of Receptor Binding Domain of SARS-CoV-2 Spike Glycoprotein with Saikosaponin, a Triterpenoid Natural Product, ChemRxiv. Camb. Camb. Open Engag, doi:10.26434/chemrxiv.12033774.v1
Große, Ruetalo, Layer, Hu, Businger et al., Quinine Inhibits Infection of Human Cell Lines with SARS-CoV-2, Viruses, doi:10.3390/v13040647
Han, Li, Liu, Wang, Zhang et al., Receptor binding and complex structures of human ACE2 to spike RBD from omicron and delta SARS-CoV-2, Cell, doi:10.1016/j.cell.2022.01.001
Ho, Wu, Chen, Li, Hsiang, Emodin blocks the SARS coronavirus spike protein and angiotensinconverting enzyme 2 interaction, Antivir. Res, doi:10.1016/j.antiviral.2006.04.014
Hoever, Baltina, Michaelis, Kondratenko, Baltina et al., Antiviral activity of glycyrrhizic acid derivatives against SARS-coronavirus, J. Med. Chem, doi:10.1021/jm0493008
Jackson, Farzan, Chen, Choe, Mechanisms of SARS-CoV-2 entry into cells, Nat. Rev. Mol. Cell Biol, doi:10.1038/s41580-021-00418-x
Kalhor, Sadeghi, Abolhasani, Kalhor, Rahimi, Repurposing of the approved small molecule drugs in order to inhibit SARS-CoV-2 S protein and human ACE2 interaction through virtual screening approaches, J. Biomol. Struct. Dyn, doi:10.1080/07391102.2020.1824816
Ke, Oton, Qu, Cortese, Zila et al., Structures and distributions of SARS-CoV-2 spike proteins on intact virions, Nature, doi:10.1038/s41586-020-2665-2
Kim, Jeon, Jang, Gotina, Won et al., a natural component of Platycodon grandiflorum, prevents both lysosome-and TMPRSS2-driven SARS-CoV-2 infection by hindering membrane fusion, Exp. Mol. Med, doi:10.1038/s12276-021-00624-9
Kumar, Gokila, Vani, Wang, Chen et al., Geranium and lemon essential oils and their active compounds downregulate angiotensin-converting enzyme 2 (ACE2), a SARS-CoV-2 spike receptor-binding domain, in epithelial cells, Plants, doi:10.3390/plants9060770
Kuznetsov, Arukuusk, Härk, Juronen, Langel et al., ACE2 peptide fragment interacts with several sites on the SARS-CoV-2 spike protein S1, bioRxiv, doi:10.1101/2020.12.29.424682
Laffeber, De Koning, Kanaar, Lebbink, Experimental Evidence for Enhanced Receptor Binding by Rapidly Spreading SARS-CoV-2 Variants, J. Mol. Biol, doi:10.1016/j.jmb.2021.167058
Lan, Ge, Yu, Shan, Zhou et al., Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor, Nature, doi:10.1038/s41586-020-2180-5
Lee, Kim, Kim, Pharmacokinetic analysis of rhein in Rheum undulatum L, J. Ethnopharmacol, doi:10.1016/S0378-8741(02)00222-2
Lehrer, Rheinstein, Ivermectin docks to the SARS-CoV-2 spike receptor-binding domain attached to ACE2, Vivo, doi:10.21873/invivo.12134
Lin, Wu, Huang, Phenols from the roots of Rheum palmatum attenuate chemotaxis in rat hepatic stellate cells, Planta Med, doi:10.1055/s-2008-1074581
Lingwan, Shagun, Pant, Nanda, Masakapalli, Antiviral phytochemicals identified in Rhododendron arboreum petals exhibited strong binding to SARS-CoV-2 MPro and Human ACE2 receptor, Preprints, doi:10.20944/preprints202008.0530.v1
Liu, Raghuvanshi, Ceylan, Bolling, Quercetin and Its Metabolites Inhibit Recombinant Human Angiotensin-Converting Enzyme 2 (ACE2) Activity, J. Agric. Food Chem, doi:10.1021/acs.jafc.0c05064
Liu, Zhang, Wei, Chen, Aviszus et al., The basis of a more contagious 501Y.V1 variant of SARS-CoV-2, Cell Res, doi:10.1038/s41422-021-00496-8
Liu, Zheng, Cheng, Li, Huang et al., Citrus fruits are rich in flavonoids for immunoregulation and potential targeting ACE2, Nat. Prod. Bioprospecting, doi:10.1007/s13659-022-00325-4
Low, Lani, Tiong, Poh, Abubakar et al., COVID-19 therapeutic potential of natural products, Int. J. Mol. Sci, doi:10.3390/ijms24119589
Mieres-Castro, Mora-Poblete, Saponins: Research Progress and Their Potential Role in the Post-COVID-19 Pandemic Era, Pharmaceutics, doi:10.3390/pharmaceutics15020348
Ogunyemi, Gyebi, Ibrahim, Olaiya, Ocheje et al., Dietary stigmastane-type saponins as promising dual-target directed inhibitors of SARS-CoV-2 proteases: A structure-based screening, RSC Adv, doi:10.1039/D1RA05976A
Overduin, Esmaili, Memtein, Fluidic Analytics. User Manual for Fluidity One-W and Fluidity One-W Serum IFU-0007v8; Fluidic Analytics, doi:10.1016/j.chemphyslip.2018.11.008
Pan, Fang, Zhang, Pan, Liu et al., Chinese herbal compounds against SARS-CoV-2: Puerarin and quercetin impair the binding of viral S-protein to ACE2 receptor, Comput. Struct. Biotechnol. J, doi:10.1016/j.csbj.2020.11.010
Patel, Vunnam, Patel, Krill, Korbitz et al., Transmission of SARS-CoV-2: An update of current literature, Eur. J. Clin. Microbiol. Infect. Dis, doi:10.1007/s10096-020-03961-1
Perrella, Coppola, Petrone, Platella, Montesarchio et al., Interference of Polydatin/Resveratrol in the ACE2:Spike Recognition during COVID-19 Infection. A Focus on Their Potential Mechanism of Action through Computational and Biochemical Assays, Biomolecules, doi:10.3390/biom11071048
Prashantha, Gouthami, Lavanya, Bhavanam, Jakhar et al., Molecular screening of antimalarial, antiviral, anti-inflammatory and HIV protease inhibitors against spike glycoprotein of coronavirus, J. Mol. Graph. Model, doi:10.1016/j.jmgm.2020.107769
Priyandoko, Molecular Docking Study of the Potential Relevance of the Natural Compounds Isoflavone and Myricetin to COVID-19, Int. J. Bioautomation, doi:10.7546/ijba.2021.25.3.000796
Prévost, Richard, Gasser, Ding, Fage et al., Impact of temperature on the affinity of SARS-CoV-2 Spike for ACE2, bioRxiv, doi:10.1101/2021.07.09.451812
Rajah, Bernier, Buchrieser, Schwartz, The Mechanism and Consequences of SARS-CoV-2 Spike-Mediated Fusion and Syncytia Formation, J. Mol. Biol, doi:10.1016/j.jmb.2021.167280
Rebello, Beyl, Lertora, Greenway, Ravussin et al., Safety and pharmacokinetics of naringenin: A randomized, controlled, single-ascending-dose clinical trial, Diabetes Obes. Metab, doi:10.1111/dom.13868
Rehan, Shafiullah, Medicinal plant-based saponins targeting COVID-19 M pro in silico, Tradit Med. Res, doi:10.53388/TMR20201130210
Rolta, Salaria, Sharma, Sharma, Kumar et al., Phytocompounds of Rheum emodi, Thymus serpyllum, and Artemisia annua Inhibit spike protein of SARS-CoV-2 binding to ACE2 receptor: In silico approach, Curr. Pharmacol. Rep, doi:10.1007/s40495-021-00259-4
Ru, Li, Wang, Zhou, Li et al., TCMSP: A database of systems pharmacology for drug discovery from herbal medicines, J. Cheminform, doi:10.1186/1758-2946-6-13
Sha, Liu, Hao, Current state-of-the-art and potential future therapeutic drugs against COVID-19, Front. Cell Dev. Biol, doi:10.3389/fcell.2023.1238027
Shakhsi-Niaei, Soureshjani, Babaheydari, In Silico Comparison of Separate or Combinatorial Effects of Potential Inhibitors of the SARS-CoV-2 Binding Site of ACE2, Iran J. Public Health, doi:10.18502/ijph.v50i5.6120
Shang, Ye, Shi, Wan, Luo et al., Structural basis of receptor recognition by SARS-CoV-2, Nature, doi:10.1038/s41586-020-2179-y
Sinha, Shakya, Prasad, Singh, Gurav et al., An in-silico evaluation of different saikosaponins for their potency against SARS-CoV-2 using NSP15 and fusion spike glycoprotein as targets, J. Biomol. Struct. Dyn, doi:10.1080/07391102.2020.1762741
Smith, Smith, Repurposing Therapeutics for COVID-19: Supercomputer-Based Docking to the SARS-CoV-2 Viral Spike Protein and Viral Spike Protein-Human ACE2 Interface
Supasa, Zhou, Dejnirattisai, Liu, Mentzer et al., Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera, Cell, doi:10.1016/j.cell.2021.02.033
Taco, Savarino, Benali, Villacrés, Raquez et al., Deep eutectic solvents for the extraction and stabilization of Ecuadorian quinoa (Chenopodium quinoa Willd.) saponins, J. Clean. Prod, doi:10.1016/j.jclepro.2022.132609
Tutunchi, Naeini, Ostadrahimi, Hosseinzadeh-Attar, Naringenin, a flavanone with antiviral and anti-inflammatory effects: A promising treatment strategy against COVID-19, Phytother. Res, doi:10.1002/ptr.6781
Van Beek, Montoro, Chemical analysis and quality control of Ginkgo biloba leaves, extracts, and phytopharmaceuticals, J. Chromatogr. A, doi:10.1016/j.chroma.2009.01.013
Van Breemen, Muchiri, Bates, Weinstein, Leier et al., Cannabinoids block cellular entry of SARS-CoV-2 and the emerging variants, J. Nat. Prod, doi:10.1021/acs.jnatprod.1c00946
Walls, Park, Tortorici, Wall, Mcguire et al., Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein, Cell, doi:10.1016/j.cell.2020.02.058
Wang, Han, Liu, Meng, He et al., Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV Spike pseudotyped virus, Phytomedicine, doi:10.1016/j.phymed.2020.153333
Wang, Huang, Chen, Lee, Yang, Inducible nitric oxide synthase inhibitors of chinese herbs III. Rheum palmatum, Planta Med, doi:10.1055/s-2002-34918
Watanabe, Allen, Wrapp, Mclellan, Crispin, Site-specific glycan analysis of the SARS-CoV-2 spike, Science, doi:10.1126/science.abb9983
Who, None
Wiese, Zemlin, Pillay, Molecules in pathogenesis: Angiotensin converting enzyme 2 (ACE2), J. Clin. Pathol, doi:10.1136/jclinpath-2020-206954
Wrapp, Wang, Corbett, Goldsmith, Hsieh et al., Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation, Science, doi:10.1126/science.abb2507
Wu, Jan, Ma, Kuo, Juan et al., Small molecules targeting severe acute respiratory syndrome human coronavirus, Proc. Natl. Acad. Sci, doi:10.1073/pnas.0403596101
Wu, Shi, Wang, Zhang, Wang, Targeting SARS-CoV-2 entry processes: The promising potential and future of host-targeted small-molecule inhibitors, Eur. J. Med. Chem, doi:10.1016/j.ejmech.2023.115923
Xu, Liu, Xiao, Zhou, Ge et al., Computational and experimental studies reveal that thymoquinone blocks the entry of coronaviruses into in vitro cells, Infect. Dis. Ther, doi:10.1007/s40121-021-00400-2
Yan, Shen, Cao, Zhang, Wang et al., Discovery of Anti-2019-nCoV Agents from Chinese Patent Drugs via Docking Screening, Preprints, doi:10.20944/preprints202002.0254.v1
Yan, Zhang, Li, Ye, Guo et al., Structural basis for the different states of the spike protein of SARS-CoV-2 in complex with ACE2, Cell Res, doi:10.1038/s41422-021-00490-0
Yang, Chen, Hamdoun, Coghi, Ng et al., Corilagin prevents SARS-CoV-2 infection by targeting RBD-ACE2 binding, Phytomedicine, doi:10.1016/j.phymed.2021.153591
Yu, Chen, Li, Absorption, disposition, and pharmacokinetics of saponins from chinese medicinal herbs: What do we know and what do we need to know more?, Curr. Drug Metab, doi:10.2174/1389200211209050577
Zeng, Yu, Wang, Liu, Xu, A potential antiviral activity of esculentoside A against binding interactions of SARS-COV-2 spike protein and angiotensin converting enzyme 2 (ACE2), Int. J. Biol. Macromol, doi:10.1016/j.ijbiomac.2021.06.017
Zhan, Ta, Tang, Hua, Wang et al., Potential antiviral activity of isorhamnetin against SARS-CoV-2 spike pseudotyped virus in vitro, Drug Dev. Res, doi:10.1002/ddr.21815
Zhang, Cai, Xiao, Lu, Peng et al., Structural impact on SARS-CoV-2 spike protein by D614G substitution, Science, doi:10.1126/science.abf2303
Zhang, Penninger, Li, Zhong, Slutsky, Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: Molecular mechanisms and potential therapeutic target, Intensive Care Med, doi:10.1007/s00134-020-05985-9
Zhu, Wang, Zhang, Li, Wang, Pharmacokinetic of rhein in healthy male volunteers following oral and retention enema administration of rhubarb extract: A single dose study, Am. J. Chin. Med, doi:10.1142/S0192415X05003508
{ 'indexed': { 'date-parts': [[2023, 12, 14]], 'date-time': '2023-12-14T00:54:10Z', 'timestamp': 1702515250966}, 'reference-count': 104, 'publisher': 'MDPI AG', 'issue': '24', 'license': [ { 'start': { 'date-parts': [[2023, 12, 13]], 'date-time': '2023-12-13T00:00:00Z', 'timestamp': 1702425600000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'funder': [ {'name': 'project Wallonie-Bruxelles/China'}, {'name': 'Fonds pour la Recherche Scientifique FNRS', 'award': ['N° CDR J.0058.21']}, {'name': 'National Key R&D Program of China', 'award': ['2021YFE0194000']}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'abstract': '<jats:p>The interaction between SARS-CoV-2 spike RBD and ACE2 proteins is a crucial step for ' 'host cell infection by the virus. Without it, the entire virion entrance mechanism is ' 'compromised. The aim of this study was to evaluate the capacity of various natural product ' 'classes, including flavonoids, anthraquinones, saponins, ivermectin, chloroquine, and ' 'erythromycin, to modulate this interaction. To accomplish this, we applied a recently ' 'developed a microfluidic diffusional sizing (MDS) technique that allows us to probe ' 'protein-protein interactions via measurements of the hydrodynamic radius (Rh) and ' 'dissociation constant (KD); the evolution of Rh is monitored in the presence of increasing ' 'concentrations of the partner protein (ACE2); and the KD is determined through a binding ' 'curve experimental design. In a second time, with the protein partners present in equimolar ' 'amounts, the Rh of the protein complex was measured in the presence of different natural ' 'products. Five of the nine natural products/extracts tested were found to modulate the ' 'formation of the protein complex. A methanol extract of Chenopodium quinoa Willd bitter seed ' 'husks (50 µg/mL; bisdesmoside saponins) and the flavonoid naringenin (1 µM) were particularly ' 'effective. This rapid selection of effective modulators will allow us to better understand ' 'agents that may prevent SARS-CoV-2 infection.</jats:p>', 'DOI': '10.3390/molecules28248072', 'type': 'journal-article', 'created': { 'date-parts': [[2023, 12, 13]], 'date-time': '2023-12-13T17:00:37Z', 'timestamp': 1702486837000}, 'page': '8072', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Microfluidic Diffusion Sizing Applied to the Study of Natural Products and Extracts That ' 'Modulate the SARS-CoV-2 Spike RBD/ACE2 Interaction', 'prefix': '10.3390', 'volume': '28', 'author': [ { 'ORCID': 'http://orcid.org/0000-0002-7997-7054', 'authenticated-orcid': False, 'given': 'Jason', 'family': 'Fauquet', 'sequence': 'first', 'affiliation': [ { 'name': 'Unit of Therapeutic Chemistry and Pharmacognosy, University of ' 'Mons (UMONS), 7000 Mons, Belgium'}]}, { 'ORCID': 'http://orcid.org/0009-0009-2264-4193', 'authenticated-orcid': False, 'given': 'Julie', 'family': 'Carette', 'sequence': 'additional', 'affiliation': [ { 'name': 'Unit of Therapeutic Chemistry and Pharmacognosy, University of ' 'Mons (UMONS), 7000 Mons, Belgium'}]}, { 'ORCID': 'http://orcid.org/0000-0002-0484-1478', 'authenticated-orcid': False, 'given': 'Pierre', 'family': 'Duez', 'sequence': 'additional', 'affiliation': [ { 'name': 'Unit of Therapeutic Chemistry and Pharmacognosy, University of ' 'Mons (UMONS), 7000 Mons, Belgium'}]}, { 'ORCID': 'http://orcid.org/0000-0002-1745-846X', 'authenticated-orcid': False, 'given': 'Jiuliang', 'family': 'Zhang', 'sequence': 'additional', 'affiliation': [ { 'name': 'College of Food Science and Technology, Huazhong Agricultural ' 'University, Wuhan 430070, China'}]}, { 'ORCID': 'http://orcid.org/0000-0002-8697-2809', 'authenticated-orcid': False, 'given': 'Amandine', 'family': 'Nachtergael', 'sequence': 'additional', 'affiliation': [ { 'name': 'Unit of Therapeutic Chemistry and Pharmacognosy, University of ' 'Mons (UMONS), 7000 Mons, Belgium'}]}], 'member': '1968', 'published-online': {'date-parts': [[2023, 12, 13]]}, 'reference': [ { 'key': 'ref_1', 'unstructured': 'WHO (2023, October 21). World Health Orgarnization. Available online: ' 'https://covid19.who.int/table.'}, { 'key': 'ref_2', 'first-page': '2564', 'article-title': 'Insuffisance Respiratoire Hypoxémique Aigüe (Syndrome de Détresse ' 'Respiratoire Aiguë [SDRA], Ou [ARDS], Acute Respiratory Distress ' 'Syndrome)', 'volume': '354', 'author': 'Bhakti', 'year': '2006', 'journal-title': 'N. Engl. J. Med.'}, { 'key': 'ref_3', 'doi-asserted-by': 'crossref', 'first-page': '2005', 'DOI': '10.1007/s10096-020-03961-1', 'article-title': 'Transmission of SARS-CoV-2: An update of current literature', 'volume': '39', 'author': 'Patel', 'year': '2020', 'journal-title': 'Eur. J. Clin. Microbiol. Infect. Dis.'}, { 'key': 'ref_4', 'first-page': '190', 'article-title': 'The role of ACE2 receptor and its age related immunity in COVID-19', 'volume': '63', 'author': 'Goel', 'year': '2020', 'journal-title': 'Int. J. Pharm. Sci. Rev. Res.'}, { 'key': 'ref_5', 'doi-asserted-by': 'crossref', 'first-page': '107769', 'DOI': '10.1016/j.jmgm.2020.107769', 'article-title': 'Molecular screening of antimalarial, antiviral, anti-inflammatory and ' 'HIV protease inhibitors against spike glycoprotein of coronavirus', 'volume': '102', 'author': 'Prashantha', 'year': '2021', 'journal-title': 'J. Mol. Graph. Model.'}, { 'key': 'ref_6', 'doi-asserted-by': 'crossref', 'unstructured': 'Rajah, M.M., Bernier, A., Buchrieser, J., and Schwartz, O. (2022). The ' 'Mechanism and Consequences of SARS-CoV-2 Spike-Mediated Fusion and ' 'Syncytia Formation. J. Mol. Biol., 434.', 'DOI': '10.1016/j.jmb.2021.167280'}, { 'key': 'ref_7', 'doi-asserted-by': 'crossref', 'first-page': '1586', 'DOI': '10.1126/science.abd4251', 'article-title': 'Distinct conformational states of SARS-CoV-2 spike protein', 'volume': '369', 'author': 'Cai', 'year': '2020', 'journal-title': 'Science'}, { 'key': 'ref_8', 'doi-asserted-by': 'crossref', 'first-page': '3', 'DOI': '10.1038/s41580-021-00418-x', 'article-title': 'Mechanisms of SARS-CoV-2 entry into cells', 'volume': '23', 'author': 'Jackson', 'year': '2022', 'journal-title': 'Nat. Rev. Mol. Cell Biol.'}, { 'key': 'ref_9', 'doi-asserted-by': 'crossref', 'first-page': '498', 'DOI': '10.1038/s41586-020-2665-2', 'article-title': 'Structures and distributions of SARS-CoV-2 spike proteins on intact ' 'virions', 'volume': '588', 'author': 'Ke', 'year': '2020', 'journal-title': 'Nature'}, { 'key': 'ref_10', 'doi-asserted-by': 'crossref', 'first-page': '330', 'DOI': '10.1126/science.abb9983', 'article-title': 'Site-specific glycan analysis of the SARS-CoV-2 spike', 'volume': '369', 'author': 'Watanabe', 'year': '2020', 'journal-title': 'Science'}, { 'key': 'ref_11', 'doi-asserted-by': 'crossref', 'first-page': '717', 'DOI': '10.1038/s41422-021-00490-0', 'article-title': 'Structural basis for the different states of the spike protein of ' 'SARS-CoV-2 in complex with ACE2', 'volume': '31', 'author': 'Yan', 'year': '2021', 'journal-title': 'Cell Res.'}, { 'key': 'ref_12', 'doi-asserted-by': 'crossref', 'first-page': '2823', 'DOI': '10.1042/CS20200477', 'article-title': 'ACE2 and gut amino acid transport', 'volume': '134', 'author': 'Camargo', 'year': '2020', 'journal-title': 'Clin. Sci.'}, { 'key': 'ref_13', 'doi-asserted-by': 'crossref', 'first-page': '285', 'DOI': '10.1136/jclinpath-2020-206954', 'article-title': 'Molecules in pathogenesis: Angiotensin converting enzyme 2 (ACE2)', 'volume': '74', 'author': 'Wiese', 'year': '2021', 'journal-title': 'J. Clin. Pathol.'}, { 'key': 'ref_14', 'doi-asserted-by': 'crossref', 'first-page': '586', 'DOI': '10.1007/s00134-020-05985-9', 'article-title': 'Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: ' 'Molecular mechanisms and potential therapeutic target', 'volume': '46', 'author': 'Zhang', 'year': '2020', 'journal-title': 'Intensive Care Med.'}, { 'key': 'ref_15', 'doi-asserted-by': 'crossref', 'first-page': '630', 'DOI': '10.1016/j.cell.2022.01.001', 'article-title': 'Receptor binding and complex structures of human ACE2 to spike RBD from ' 'omicron and delta SARS-CoV-2', 'volume': '185', 'author': 'Han', 'year': '2022', 'journal-title': 'Cell'}, { 'key': 'ref_16', 'doi-asserted-by': 'crossref', 'first-page': '2362', 'DOI': '10.1021/acsinfecdis.1c00047', 'article-title': 'Antibody Affinity Governs the Inhibition of SARS-CoV-2 Spike/ACE2 ' 'Binding in Patient Serum', 'volume': '7', 'author': 'Fiedler', 'year': '2021', 'journal-title': 'ACS Infect. Dis.'}, { 'key': 'ref_17', 'doi-asserted-by': 'crossref', 'first-page': '333', 'DOI': '10.1021/acsnano.5b04713', 'article-title': 'Microfluidic diffusion analysis of the sizes and interactions of ' 'proteins under native solution conditions', 'volume': '10', 'author': 'Arosio', 'year': '2016', 'journal-title': 'ACS Nano'}, { 'key': 'ref_18', 'doi-asserted-by': 'crossref', 'first-page': '509', 'DOI': '10.1080/13880209.2022.2039215', 'article-title': 'The vital role of animal, marine, and microbial natural products ' 'against COVID-19', 'volume': '60', 'author': 'Alqathama', 'year': '2022', 'journal-title': 'Pharm. Biol.'}, { 'key': 'ref_19', 'doi-asserted-by': 'crossref', 'unstructured': 'Frediansyah, A., Sofyantoro, F., Alhumaid, S., Al Mutair, A., Albayat, ' 'H., Altaweil, H.I., Al-Afghani, H.M., AlRamadhan, A.A., AlGhazal, M.R., ' 'and Turkistani, S.A. (2022). Microbial natural products with antiviral ' 'activities, including anti-SARS-CoV-2: A review. Molecules, 27.', 'DOI': '10.3390/molecules27134305'}, { 'key': 'ref_20', 'doi-asserted-by': 'crossref', 'unstructured': 'Low, Z., Lani, R., Tiong, V., Poh, C., AbuBakar, S., and Hassandarvish, ' 'P. (2023). COVID-19 therapeutic potential of natural products. Int. J. ' 'Mol. Sci., 24.', 'DOI': '10.20944/preprints202305.0492.v1'}, { 'key': 'ref_21', 'doi-asserted-by': 'crossref', 'unstructured': 'Lingwan, M., Shagun, S., Pant, Y., Nanda, R., and Masakapalli, S. ' '(2020). Antiviral phytochemicals identified in Rhododendron arboreum ' 'petals exhibited strong binding to SARS-CoV-2 MPro and Human ACE2 ' 'receptor. Preprints, 2020080530.', 'DOI': '10.20944/preprints202008.0530.v1'}, { 'key': 'ref_22', 'doi-asserted-by': 'crossref', 'unstructured': 'Liu, W., Zheng, W., Cheng, L., Li, M., Huang, J., Bao, S., Xu, Q., and ' 'Ma, Z. (2022). Citrus fruits are rich in flavonoids for immunoregulation ' 'and potential targeting ACE2. Nat. Prod. Bioprospecting, 12.', 'DOI': '10.1007/s13659-022-00325-4'}, { 'key': 'ref_23', 'doi-asserted-by': 'crossref', 'first-page': '13982', 'DOI': '10.1021/acs.jafc.0c05064', 'article-title': 'Quercetin and Its Metabolites Inhibit Recombinant Human ' 'Angiotensin-Converting Enzyme 2 (ACE2) Activity', 'volume': '68', 'author': 'Liu', 'year': '2020', 'journal-title': 'J. Agric. Food Chem.'}, { 'key': 'ref_24', 'doi-asserted-by': 'crossref', 'first-page': '3518', 'DOI': '10.1016/j.csbj.2020.11.010', 'article-title': 'Chinese herbal compounds against SARS-CoV-2: Puerarin and quercetin ' 'impair the binding of viral S-protein to ACE2 receptor', 'volume': '18', 'author': 'Pan', 'year': '2020', 'journal-title': 'Comput. Struct. Biotechnol. J.'}, { 'key': 'ref_25', 'doi-asserted-by': 'crossref', 'first-page': '271', 'DOI': '10.7546/ijba.2021.25.3.000796', 'article-title': 'Molecular Docking Study of the Potential Relevance of the Natural ' 'Compounds Isoflavone and Myricetin to COVID-19', 'volume': '25', 'author': 'Priyandoko', 'year': '2021', 'journal-title': 'Int. J. Bioautomation'}, { 'key': 'ref_26', 'first-page': '1028', 'article-title': 'In Silico Comparison of Separate or Combinatorial Effects of Potential ' 'Inhibitors of the SARS-CoV-2 Binding Site of ACE2', 'volume': '50', 'author': 'Soureshjani', 'year': '2021', 'journal-title': 'Iran J. Public Health'}, { 'key': 'ref_27', 'doi-asserted-by': 'crossref', 'first-page': '3137', 'DOI': '10.1002/ptr.6781', 'article-title': 'Naringenin, a flavanone with antiviral and anti-inflammatory effects: A ' 'promising treatment strategy against COVID-19', 'volume': '30', 'author': 'Tutunchi', 'year': '2020', 'journal-title': 'Phytother. Res.'}, { 'key': 'ref_28', 'first-page': '3263', 'article-title': 'In Silico study the inhibition of angiotensin converting enzyme 2 ' 'receptor of COVID-19 by Ammoides verticillata components harvested from ' 'Western Algeria', 'volume': '39', 'author': 'Abdelli', 'year': '2020', 'journal-title': 'J. Biomol. Struct. Dyn.'}, { 'key': 'ref_29', 'doi-asserted-by': 'crossref', 'unstructured': 'Badraoui, R., Saoudi, M., Hamadou, W.S., Elkahoui, S., Siddiqui, A.J., ' 'Alam, J.M., Jamal, A., Adnan, M., Suliemen, A.M.E., and Alreshidi, M.M. ' '(2022). Antiviral effects of artemisinin and Its derivatives against ' 'SARS-CoV-2 main protease: Computational evidences and interactions with ' 'ACE2 allelic variants. Pharmaceuticals, 15.', 'DOI': '10.3390/ph15020129'}, { 'key': 'ref_30', 'doi-asserted-by': 'crossref', 'first-page': '112895', 'DOI': '10.1016/j.jep.2020.112895', 'article-title': 'Astragali Radix (Huangqi): A promising edible immunomodulatory herbal ' 'medicine', 'volume': '258', 'author': 'Chen', 'year': '2020', 'journal-title': 'J. Ethnopharmacol.'}, { 'key': 'ref_31', 'doi-asserted-by': 'crossref', 'unstructured': 'Goswami, T., and Bagchi, B. (2020). Molecular Docking study of Receptor ' 'Binding Domain of SARS-CoV-2 Spike Glycoprotein with Saikosaponin, a ' 'Triterpenoid Natural Product. ChemRxiv. Camb. Camb. Open Engag.', 'DOI': '10.26434/chemrxiv.12033774'}, { 'key': 'ref_32', 'doi-asserted-by': 'crossref', 'first-page': '135', 'DOI': '10.1007/s40495-021-00259-4', 'article-title': 'Phytocompounds of Rheum emodi, Thymus serpyllum, and Artemisia annua ' 'Inhibit spike protein of SARS-CoV-2 binding to ACE2 receptor: In silico ' 'approach', 'volume': '7', 'author': 'Rolta', 'year': '2021', 'journal-title': 'Curr. Pharmacol. Rep.'}, { 'key': 'ref_33', 'first-page': '3244', 'article-title': 'An in-silico evaluation of different saikosaponins for their potency ' 'against SARS-CoV-2 using NSP15 and fusion spike glycoprotein as targets', 'volume': '39', 'author': 'Sinha', 'year': '2021', 'journal-title': 'J. Biomol. Struct. Dyn.'}, { 'key': 'ref_34', 'doi-asserted-by': 'crossref', 'first-page': '2248', 'DOI': '10.1016/j.ijbiomac.2021.06.017', 'article-title': 'A potential antiviral activity of esculentoside A against binding ' 'interactions of SARS-COV-2 spike protein and angiotensin converting ' 'enzyme 2 (ACE2)', 'volume': '183', 'author': 'Zeng', 'year': '2021', 'journal-title': 'Int. J. Biol. Macromol.'}, { 'key': 'ref_35', 'doi-asserted-by': 'crossref', 'first-page': '1202', 'DOI': '10.2174/1381612827666210125121954', 'article-title': 'The computational intervention of macrolide antibiotics in the ' 'treatment of COVID-19', 'volume': '27', 'author': 'Anwar', 'year': '2021', 'journal-title': 'Curr. Pharm. Des.'}, { 'key': 'ref_36', 'doi-asserted-by': 'crossref', 'first-page': '106119', 'DOI': '10.1016/j.ijantimicag.2020.106119', 'article-title': 'In Silico study of azithromycin, chloroquine and hydroxychloroquine and ' 'their potential mechanisms of action against SARS-CoV-2 infection', 'volume': '56', 'author': 'Braz', 'year': '2020', 'journal-title': 'Int. J. Antimicrob. Agents'}, { 'key': 'ref_37', 'doi-asserted-by': 'crossref', 'first-page': '1299', 'DOI': '10.1080/07391102.2020.1824816', 'article-title': 'Repurposing of the approved small molecule drugs in order to inhibit ' 'SARS-CoV-2 S protein and human ACE2 interaction through virtual ' 'screening approaches', 'volume': '40', 'author': 'Kalhor', 'year': '2022', 'journal-title': 'J. Biomol. Struct. Dyn.'}, { 'key': 'ref_38', 'doi-asserted-by': 'crossref', 'first-page': '3023', 'DOI': '10.21873/invivo.12134', 'article-title': 'Ivermectin docks to the SARS-CoV-2 spike receptor-binding domain ' 'attached to ACE2', 'volume': '34', 'author': 'Lehrer', 'year': '2020', 'journal-title': 'In Vivo'}, { 'key': 'ref_39', 'doi-asserted-by': 'crossref', 'first-page': '17699', 'DOI': '10.1038/s41598-020-74715-4', 'article-title': 'Molecular docking study of potential phytochemicals and their effects ' 'on the complex of SARS-CoV2 spike protein and human ACE2', 'volume': '10', 'author': 'Basu', 'year': '2020', 'journal-title': 'Sci. Rep.'}, { 'key': 'ref_40', 'doi-asserted-by': 'crossref', 'first-page': '14571', 'DOI': '10.18632/aging.203098', 'article-title': 'Revealing the therapeutic targets and molecular mechanisms of ' 'emodin-treated coronavirus disease 2019 via a systematic study of ' 'network pharmacology', 'volume': '13', 'author': 'Du', 'year': '2021', 'journal-title': 'Aging'}, { 'key': 'ref_41', 'doi-asserted-by': 'crossref', 'first-page': '1124', 'DOI': '10.1002/ddr.21815', 'article-title': 'Potential antiviral activity of isorhamnetin against SARS-CoV-2 spike ' 'pseudotyped virus in vitro', 'volume': '82', 'author': 'Zhan', 'year': '2021', 'journal-title': 'Drug Dev. Res.'}, { 'key': 'ref_42', 'doi-asserted-by': 'crossref', 'first-page': '1793', 'DOI': '10.1021/acs.jpclett.0c03119', 'article-title': 'Kobophenol A Inhibits Binding of Host ACE2 Receptor with Spike RBD ' 'Domain of SARS-CoV-2, a Lead Compound for Blocking COVID-19', 'volume': '12', 'author': 'Gangadevi', 'year': '2021', 'journal-title': 'J. Phys. Chem. Lett.'}, { 'key': 'ref_43', 'doi-asserted-by': 'crossref', 'unstructured': 'Perrella, F., Coppola, F., Petrone, A., Platella, C., Montesarchio, D., ' 'Stringaro, A., Ravagnan, G., Fuggetta, M.P., Rega, N., and Musumeci, D. ' '(2021). Interference of Polydatin/Resveratrol in the ACE2:Spike ' 'Recognition during COVID-19 Infection. A Focus on Their Potential ' 'Mechanism of Action through Computational and Biochemical Assays. ' 'Biomolecules, 11.', 'DOI': '10.3390/biom11071048'}, { 'key': 'ref_44', 'doi-asserted-by': 'crossref', 'first-page': '634176', 'DOI': '10.3389/fphar.2021.634176', 'article-title': '1,2,3,4,6-Pentagalloyl Glucose, a RBD-ACE2 Binding Inhibitor to Prevent ' 'SARS-CoV-2 Infection', 'volume': '12', 'author': 'Chen', 'year': '2021', 'journal-title': 'Front. Pharmacol.'}, { 'key': 'ref_45', 'doi-asserted-by': 'crossref', 'first-page': '153591', 'DOI': '10.1016/j.phymed.2021.153591', 'article-title': 'Corilagin prevents SARS-CoV-2 infection by targeting RBD-ACE2 binding', 'volume': '87', 'author': 'Yang', 'year': '2021', 'journal-title': 'Phytomedicine'}, { 'key': 'ref_46', 'doi-asserted-by': 'crossref', 'first-page': '1111', 'DOI': '10.2147/DDDT.S292805', 'article-title': 'Withanone from Withania somnifera attenuates SARS-CoV-2 RBD and host ' 'ACE2 interactions to rescue spike protein induced pathologies in ' 'humanized zebrafish model', 'volume': '15', 'author': 'Balkrishna', 'year': '2021', 'journal-title': 'Drug Des. Devel. Ther.'}, { 'key': 'ref_47', 'doi-asserted-by': 'crossref', 'first-page': '22195', 'DOI': '10.1038/s41598-021-01690-9', 'article-title': 'Common cardiac medications potently inhibit ACE2 binding to the ' 'SARS-CoV-2 Spike, and block virus penetration and infectivity in human ' 'lung cells', 'volume': '11', 'author': 'Caohuy', 'year': '2021', 'journal-title': 'Sci. Rep.'}, { 'key': 'ref_48', 'first-page': 'e1828792', 'article-title': 'ACE2: S1 RBD interaction-targeted peptides and small molecules as ' 'potential COVID-19 therapeutics', 'volume': '2021', 'author': 'Chitsike', 'year': '2021', 'journal-title': 'Adv. Pharmacol. Pharm. Sci.'}, { 'key': 'ref_49', 'doi-asserted-by': 'crossref', 'first-page': '105255', 'DOI': '10.1016/j.phrs.2020.105255', 'article-title': 'Naringenin is a powerful inhibitor of SARS-CoV-2 infection in vitro', 'volume': '163', 'author': 'Clementi', 'year': '2021', 'journal-title': 'Pharmacol. Res.'}, { 'key': 'ref_50', 'doi-asserted-by': 'crossref', 'first-page': '176', 'DOI': '10.1021/acs.jnatprod.1c00946', 'article-title': 'Cannabinoids block cellular entry of SARS-CoV-2 and the emerging ' 'variants', 'volume': '85', 'author': 'Muchiri', 'year': '2022', 'journal-title': 'J. Nat. Prod.'}, { 'key': 'ref_51', 'doi-asserted-by': 'crossref', 'first-page': '956', 'DOI': '10.1038/s12276-021-00624-9', 'article-title': 'Platycodin D, a natural component of Platycodon grandiflorum, prevents ' 'both lysosome- and TMPRSS2-driven SARS-CoV-2 infection by hindering ' 'membrane fusion', 'volume': '53', 'author': 'Kim', 'year': '2021', 'journal-title': 'Exp. Mol. Med.'}, { 'key': 'ref_52', 'doi-asserted-by': 'crossref', 'unstructured': 'Senthil Kumar, K.J., Gokila Vani, M., Wang, C.-S., Chen, C.-C., Chen, ' 'Y.-C., Lu, L.-P., Huang, C.-H., Lai, C.-S., and Wang, S.-Y. (2020). ' 'Geranium and lemon essential oils and their active compounds ' 'downregulate angiotensin-converting enzyme 2 (ACE2), a SARS-CoV-2 spike ' 'receptor-binding domain, in epithelial cells. Plants, 9.', 'DOI': '10.3390/plants9060770'}, { 'key': 'ref_53', 'doi-asserted-by': 'crossref', 'first-page': '483', 'DOI': '10.1007/s40121-021-00400-2', 'article-title': 'Computational and experimental studies reveal that thymoquinone blocks ' 'the entry of coronaviruses into in vitro cells', 'volume': '10', 'author': 'Xu', 'year': '2021', 'journal-title': 'Infect. Dis. Ther.'}, { 'key': 'ref_54', 'doi-asserted-by': 'crossref', 'first-page': '104787', 'DOI': '10.1016/j.antiviral.2020.104787', 'article-title': 'The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 ' 'in vitro', 'volume': '178', 'author': 'Caly', 'year': '2020', 'journal-title': 'Antivir. Res.'}, { 'key': 'ref_55', 'doi-asserted-by': 'crossref', 'unstructured': 'Große, M., Ruetalo, N., Layer, M., Hu, D., Businger, R., Rheber, S., ' 'Setz, C., Rauch, P., Auth, J., and Fröba, M. (2021). Quinine Inhibits ' 'Infection of Human Cell Lines with SARS-CoV-2. Viruses, 13.', 'DOI': '10.3390/v13040647'}, { 'key': 'ref_56', 'doi-asserted-by': 'crossref', 'first-page': '153333', 'DOI': '10.1016/j.phymed.2020.153333', 'article-title': 'Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit ' 'viropexis of 2019-nCoV Spike pseudotyped virus', 'volume': '79', 'author': 'Wang', 'year': '2020', 'journal-title': 'Phytomedicine'}, { 'key': 'ref_57', 'doi-asserted-by': 'crossref', 'first-page': '92', 'DOI': '10.1016/j.antiviral.2006.04.014', 'article-title': 'Emodin blocks the SARS coronavirus spike protein and ' 'angiotensin-converting enzyme 2 interaction', 'volume': '74', 'author': 'Ho', 'year': '2007', 'journal-title': 'Antivir. Res.'}, { 'key': 'ref_58', 'doi-asserted-by': 'crossref', 'first-page': '215', 'DOI': '10.1038/s41586-020-2180-5', 'article-title': 'Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ' 'ACE2 receptor', 'volume': '581', 'author': 'Lan', 'year': '2020', 'journal-title': 'Nature'}, { 'key': 'ref_59', 'doi-asserted-by': 'crossref', 'first-page': 'e70658', 'DOI': '10.7554/eLife.70658', 'article-title': 'Effects of common mutations in the SARS-CoV-2 Spike RBD and its ligand, ' 'the human ACE2 receptor on binding affinity and kinetics', 'volume': '10', 'author': 'Barton', 'year': '2021', 'journal-title': 'eLife'}, { 'key': 'ref_60', 'doi-asserted-by': 'crossref', 'unstructured': 'Laffeber, C., de Koning, K., Kanaar, R., and Lebbink, J.H.G. (2021). ' 'Experimental Evidence for Enhanced Receptor Binding by Rapidly Spreading ' 'SARS-CoV-2 Variants. J. Mol. Biol., 433.', 'DOI': '10.1101/2021.02.22.432357'}, { 'key': 'ref_61', 'doi-asserted-by': 'crossref', 'first-page': '720', 'DOI': '10.1038/s41422-021-00496-8', 'article-title': 'The basis of a more contagious 501Y.V1 variant of SARS-CoV-2', 'volume': '31', 'author': 'Liu', 'year': '2021', 'journal-title': 'Cell Res.'}, { 'key': 'ref_62', 'doi-asserted-by': 'crossref', 'first-page': '221', 'DOI': '10.1038/s41586-020-2179-y', 'article-title': 'Structural basis of receptor recognition by SARS-CoV-2', 'volume': '581', 'author': 'Shang', 'year': '2020', 'journal-title': 'Nature'}, { 'key': 'ref_63', 'doi-asserted-by': 'crossref', 'first-page': '2201', 'DOI': '10.1016/j.cell.2021.02.033', 'article-title': 'Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent ' 'and vaccine sera', 'volume': '184', 'author': 'Supasa', 'year': '2021', 'journal-title': 'Cell'}, { 'key': 'ref_64', 'doi-asserted-by': 'crossref', 'unstructured': 'Prévost, J., Richard, J., Gasser, R., Ding, S., Fage, C., Anand, S.P., ' 'Adam, D., Vergara, N.G., Tauzin, A., and Benlarbi, M. (2021). Impact of ' 'temperature on the affinity of SARS-CoV-2 Spike for ACE2. bioRxiv.', 'DOI': '10.1101/2021.07.09.451812'}, { 'key': 'ref_65', 'doi-asserted-by': 'crossref', 'first-page': '1260', 'DOI': '10.1126/science.abb2507', 'article-title': 'Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation', 'volume': '367', 'author': 'Wrapp', 'year': '2020', 'journal-title': 'Science'}, { 'key': 'ref_66', 'unstructured': '(2023, October 25). ReactionBiology. Reaction Biology. Available online: ' 'https://www.reactionbiology.com/sites/default/files/Images/Content/Biophysical_Assay/SPR_S%20protein%20ACE2_ReactionBiology_V2.pdf.'}, { 'key': 'ref_67', 'doi-asserted-by': 'crossref', 'unstructured': 'Allen, J.D., Watanabe, Y., Chawla, H., Newby, M.L., and Crispin, M. ' '(2021). Subtle Influence of ACE2 Glycan Processing on SARS-CoV-2 ' 'Recognition. J. Mol. Biol., 433.', 'DOI': '10.1016/j.jmb.2020.166762'}, { 'key': 'ref_68', 'doi-asserted-by': 'crossref', 'unstructured': 'Kuznetsov, A., Arukuusk, P., Härk, H., Juronen, E., Langel, Ü., Ustav, ' 'M., and Järv, J. (2020). ACE2 peptide fragment interacts with several ' 'sites on the SARS-CoV-2 spike protein S1. bioRxiv.', 'DOI': '10.1101/2020.12.29.424682'}, { 'key': 'ref_69', 'doi-asserted-by': 'crossref', 'first-page': '281', 'DOI': '10.1016/j.cell.2020.02.058', 'article-title': 'Structure, Function, and Antigenicity of the SARS-CoV-2 Spike ' 'Glycoprotein', 'volume': '181', 'author': 'Walls', 'year': '2020', 'journal-title': 'Cell'}, { 'key': 'ref_70', 'doi-asserted-by': 'crossref', 'first-page': '525', 'DOI': '10.1126/science.abf2303', 'article-title': 'Structural impact on SARS-CoV-2 spike protein by D614G substitution', 'volume': '372', 'author': 'Zhang', 'year': '2021', 'journal-title': 'Science'}, { 'key': 'ref_71', 'doi-asserted-by': 'crossref', 'first-page': '13', 'DOI': '10.1186/1758-2946-6-13', 'article-title': 'TCMSP: A database of systems pharmacology for drug discovery from ' 'herbal medicines', 'volume': '6', 'author': 'Ru', 'year': '2014', 'journal-title': 'J. Cheminform.'}, { 'key': 'ref_72', 'doi-asserted-by': 'crossref', 'unstructured': 'Smith, M.D., and Smith, J.C. (ChemRxiv, 2020). Repurposing Therapeutics ' 'for COVID-19: Supercomputer-Based Docking to the SARS-CoV-2 Viral Spike ' 'Protein and Viral Spike Protein-Human ACE2 Interface, ChemRxiv, ' 'preprint.', 'DOI': '10.26434/chemrxiv.11871402'}, { 'key': 'ref_73', 'doi-asserted-by': 'crossref', 'first-page': '33', 'DOI': '10.1016/j.mrgentox.2014.04.014', 'article-title': 'Effects of chemopreventive natural products on non-homologous ' 'end-joining DNA double-strand break repair', 'volume': '768', 'author': 'Charles', 'year': '2014', 'journal-title': 'Mutat. Res./Genet. Toxicol. Environ. Mutagen.'}, { 'key': 'ref_74', 'doi-asserted-by': 'crossref', 'first-page': '91', 'DOI': '10.1111/dom.13868', 'article-title': 'Safety and pharmacokinetics of naringenin: A randomized, controlled, ' 'single-ascending-dose clinical trial', 'volume': '22', 'author': 'Rebello', 'year': '2020', 'journal-title': 'Diabetes Obes. Metab.'}, { 'key': 'ref_75', 'doi-asserted-by': 'crossref', 'first-page': '733', 'DOI': '10.1016/j.ijid.2022.07.003', 'article-title': 'The effect of ivermectin on the viral load and culture viability in ' 'early treatment of nonhospitalized patients with mild COVID-19—A ' 'double-blind, randomized placebo-controlled trial', 'volume': '122', 'author': 'Biber', 'year': '2022', 'journal-title': 'Int. J. Infect. Dis.'}, { 'key': 'ref_76', 'doi-asserted-by': 'crossref', 'first-page': '42', 'DOI': '10.1208/s12248-007-9000-9', 'article-title': 'The pharmacokinetics and interactions of ivermectin in humans—A ' 'mini-review', 'volume': '10', 'year': '2008', 'journal-title': 'AAPS J.'}, { 'key': 'ref_77', 'doi-asserted-by': 'crossref', 'first-page': '5', 'DOI': '10.1016/S0378-8741(02)00222-2', 'article-title': 'Pharmacokinetic analysis of rhein in Rheum undulatum L.', 'volume': '84', 'author': 'Lee', 'year': '2003', 'journal-title': 'J. Ethnopharmacol.'}, { 'key': 'ref_78', 'doi-asserted-by': 'crossref', 'first-page': '839', 'DOI': '10.1142/S0192415X05003508', 'article-title': 'Pharmacokinetic of rhein in healthy male volunteers following oral and ' 'retention enema administration of rhubarb extract: A single dose study', 'volume': '33', 'author': 'Zhu', 'year': '2005', 'journal-title': 'Am. J. Chin. Med.'}, { 'key': 'ref_79', 'doi-asserted-by': 'crossref', 'unstructured': 'Mieres-Castro, D., and Mora-Poblete, F. (2023). Saponins: Research ' 'Progress and Their Potential Role in the Post-COVID-19 Pandemic Era. ' 'Pharmaceutics, 15.', 'DOI': '10.3390/pharmaceutics15020348'}, { 'key': 'ref_80', 'doi-asserted-by': 'crossref', 'first-page': '33380', 'DOI': '10.1039/D1RA05976A', 'article-title': 'Dietary stigmastane-type saponins as promising dual-target directed ' 'inhibitors of SARS-CoV-2 proteases: A structure-based screening', 'volume': '11', 'author': 'Ogunyemi', 'year': '2021', 'journal-title': 'RSC Adv.'}, { 'key': 'ref_81', 'doi-asserted-by': 'crossref', 'first-page': '21', 'DOI': '10.53388/TMR20201130210', 'article-title': 'Medicinal plant-based saponins targeting COVID-19 Mpro in silico', 'volume': '6', 'author': 'Rehan', 'year': '2021', 'journal-title': 'Tradit Med. Res.'}, { 'key': 'ref_82', 'doi-asserted-by': 'crossref', 'first-page': '9', 'DOI': '10.1007/s40203-020-00071-w', 'article-title': 'In Silico investigation of saponins and tannins as potential inhibitors ' 'of SARS-CoV-2 main protease (Mpro)', 'volume': '9', 'author': 'Falade', 'year': '2021', 'journal-title': 'Silico Pharmacol.'}, { 'key': 'ref_83', 'doi-asserted-by': 'crossref', 'unstructured': 'Chen, H., and Du, Q. (2020). Potential Natural Compounds for Preventing ' 'SARS-CoV-2 (2019-nCoV) Infection. Preprints.', 'DOI': '10.20944/preprints202001.0358.v3'}, { 'key': 'ref_84', 'doi-asserted-by': 'crossref', 'unstructured': 'Yan, Y., Shen, X., Cao, Y., Zhang, J., Wang, Y., and Cheng, Y. (2020). ' 'Discovery of Anti-2019-nCoV Agents from Chinese Patent Drugs via Docking ' 'Screening. Preprints, 2020020254.', 'DOI': '10.20944/preprints202002.0254.v1'}, { 'key': 'ref_85', 'doi-asserted-by': 'crossref', 'first-page': '612', 'DOI': '10.1111/j.1440-1681.2006.04415.x', 'article-title': 'Antiviral effects of saikosaponins on human coronavirus 229E in vitro', 'volume': '33', 'author': 'Cheng', 'year': '2006', 'journal-title': 'Clin. Exp. Pharmacol. Physiol.'}, { 'key': 'ref_86', 'doi-asserted-by': 'crossref', 'first-page': '2045', 'DOI': '10.1016/S0140-6736(03)13615-X', 'article-title': 'Glycyrrhizin, an active component of liquorice roots, and replication ' 'of SARS-associated coronavirus', 'volume': '361', 'author': 'Cinatl', 'year': '2003', 'journal-title': 'Lancet'}, { 'key': 'ref_87', 'doi-asserted-by': 'crossref', 'first-page': '69', 'DOI': '10.1016/j.jcv.2004.03.003', 'article-title': 'In Vitro susceptibility of 10 clinical isolates of SARS coronavirus to ' 'selected antiviral compounds', 'volume': '31', 'author': 'Chen', 'year': '2004', 'journal-title': 'J. Clin. Virol.'}, { 'key': 'ref_88', 'doi-asserted-by': 'crossref', 'first-page': '1256', 'DOI': '10.1021/jm0493008', 'article-title': 'Antiviral activity of glycyrrhizic acid derivatives against ' 'SARS-coronavirus', 'volume': '48', 'author': 'Hoever', 'year': '2005', 'journal-title': 'J. Med. Chem.'}, { 'key': 'ref_89', 'doi-asserted-by': 'crossref', 'first-page': '10012', 'DOI': '10.1073/pnas.0403596101', 'article-title': 'Small molecules targeting severe acute respiratory syndrome human ' 'coronavirus', 'volume': '101', 'author': 'Wu', 'year': '2004', 'journal-title': 'Proc. Natl. Acad. Sci. USA'}, { 'key': 'ref_90', 'doi-asserted-by': 'crossref', 'first-page': '577', 'DOI': '10.2174/1389200211209050577', 'article-title': 'Absorption, disposition, and pharmacokinetics of saponins from chinese ' 'medicinal herbs: What do we know and what do we need to know more?', 'volume': '13', 'author': 'Yu', 'year': '2012', 'journal-title': 'Curr. Drug Metab.'}, { 'key': 'ref_91', 'doi-asserted-by': 'crossref', 'first-page': '132609', 'DOI': '10.1016/j.jclepro.2022.132609', 'article-title': 'Deep eutectic solvents for the extraction and stabilization of ' 'Ecuadorian quinoa (Chenopodium quinoa Willd.) saponins', 'volume': '363', 'author': 'Taco', 'year': '2022', 'journal-title': 'J. Clean. Prod.'}, { 'key': 'ref_92', 'doi-asserted-by': 'crossref', 'unstructured': 'Sha, A., Liu, Y., and Hao, H. (2023). Current state-of-the-art and ' 'potential future therapeutic drugs against COVID-19. Front. Cell Dev. ' 'Biol., 11.', 'DOI': '10.3389/fcell.2023.1238027'}, { 'key': 'ref_93', 'doi-asserted-by': 'crossref', 'first-page': '115923', 'DOI': '10.1016/j.ejmech.2023.115923', 'article-title': 'Targeting SARS-CoV-2 entry processes: The promising potential and ' 'future of host-targeted small-molecule inhibitors', 'volume': '263', 'author': 'Wu', 'year': '2024', 'journal-title': 'Eur. J. Med. Chem.'}, { 'key': 'ref_94', 'doi-asserted-by': 'crossref', 'first-page': '1246', 'DOI': '10.1055/s-2008-1074581', 'article-title': 'Phenols from the roots of Rheum palmatum attenuate chemotaxis in rat ' 'hepatic stellate cells', 'volume': '74', 'author': 'Lin', 'year': '2008', 'journal-title': 'Planta Med.'}, { 'key': 'ref_95', 'unstructured': '(2023, November 18). Sigma-Aldrich. Available online: ' 'https://www.sigmaaldrich.com/certificates/Graphics/COfAInfo/fluka/pdf/rtc/PHR1380_LRAC6468.pdf.'}, { 'key': 'ref_96', 'doi-asserted-by': 'crossref', 'first-page': '2002', 'DOI': '10.1016/j.chroma.2009.01.013', 'article-title': 'Chemical analysis and quality control of Ginkgo biloba leaves, ' 'extracts, and phytopharmaceuticals', 'volume': '1216', 'author': 'Montoro', 'year': '2009', 'journal-title': 'J. Chromatogr. A'}, { 'key': 'ref_97', 'doi-asserted-by': 'crossref', 'first-page': '869', 'DOI': '10.1055/s-2002-34918', 'article-title': 'Inducible nitric oxide synthase inhibitors of chinese herbs III. Rheum ' 'palmatum', 'volume': '68', 'author': 'Wang', 'year': '2002', 'journal-title': 'Planta Med.'}, { 'key': 'ref_98', 'unstructured': 'EMA (2020). Assessment Report on Rheum palmatum L. and Rheum Officinale ' 'Baillon, Radix.'}, { 'key': 'ref_99', 'unstructured': '(2023, October 21). Fluidic Analytics. Available online: ' 'https://www.fluidic.com/.'}, { 'key': 'ref_100', 'unstructured': 'Fluidic Analytics (2022). User Guide for Fluidity™ One-M IFU-0011 v4, ' 'Fluidic Analytics.'}, { 'key': 'ref_101', 'unstructured': 'Fluidic Analytics (2021). User Manual for Fluidity One-W and Fluidity ' 'One-W Serum IFU-0007v8, Fluidic Analytics.'}, { 'key': 'ref_102', 'doi-asserted-by': 'crossref', 'first-page': '73', 'DOI': '10.1016/j.chemphyslip.2018.11.008', 'article-title': 'Memtein: The fundamental unit of membrane-protein structure and ' 'function', 'volume': '218', 'author': 'Overduin', 'year': '2019', 'journal-title': 'Chem. Phys. Lipids'}, { 'key': 'ref_103', 'unstructured': '(2022, April 09). Fluidic Analytics. Available online: ' 'https://www.fluidic.com/resources/hydrodynamicradius-and-protein-weight/.'}, { 'key': 'ref_104', 'unstructured': '(2023, October 23). Fluidic Analytics. Available online: ' 'https://www.fluidic.com/calculators-page/.'}], 'container-title': 'Molecules', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://www.mdpi.com/1420-3049/28/24/8072/pdf', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 12, 13]], 'date-time': '2023-12-13T17:09:20Z', 'timestamp': 1702487360000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.mdpi.com/1420-3049/28/24/8072'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2023, 12, 13]]}, 'references-count': 104, 'journal-issue': {'issue': '24', 'published-online': {'date-parts': [[2023, 12]]}}, 'alternative-id': ['molecules28248072'], 'URL': 'http://dx.doi.org/10.3390/molecules28248072', 'relation': {}, 'ISSN': ['1420-3049'], 'subject': [ 'Chemistry (miscellaneous)', 'Analytical Chemistry', 'Organic Chemistry', 'Physical and Theoretical Chemistry', 'Molecular Medicine', 'Drug Discovery', 'Pharmaceutical Science'], 'container-title-short': 'Molecules', 'published': {'date-parts': [[2023, 12, 13]]}}
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