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Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

Theoretical Study of the Molecular Mechanism of Maxingyigan Decoction Against COVID-19: Network Pharmacology-based Strategy

Author(s): Mingzhu Wang, Deyu Fu*, Lei Yao and Jianhua Li

Volume 24, Issue 2, 2021

Published on: 06 August, 2020

Page: [294 - 305] Pages: 12

DOI: 10.2174/1386207323666200806164635

Price: $65

Abstract

Aim and Objective: Maxingyigan (MXYG) decoction is a traditional Chinese medicine (TCM) prescription. However, how MXYG acts against coronavirus disease 2019 (COVID-19) is not known. We investigated the active ingredients and the therapeutic targets of MXYG decoction against COVID-19.

Methods: A network pharmacology strategy involving drug-likeness evaluation, prediction of oral bioavailability, network analyses, and virtual molecular docking was used to predict the mechanism of action of MXYG against COVID-19.

Results: Thirty-three core COVID-19-related targets were identified from 1023 gene targets through analyses of protein–protein interactions. Eighty-six active ingredients of MXYG decoction hit by 19 therapeutic targets were screened out by analyses of a compound–compound target network. Via network topology, three “hub” gene targets (interleukin (IL-6), caspase-3, IL-4) and three key components (quercetin, formononetin, luteolin) were recognized and verified by molecular docking. Compared with control compounds (ribavirin, arbidol), the docking score of quercetin to the IL-6 receptor was highest, with a score of 5. Furthermore, the scores of three key components to SARS-CoV-2 are large as 4, 5, and 5, respectively, which are even better than those of ribavirin at 3. Bioinformatics analyses revealed that MXYG could prevent and treat COVID-19 through anti-inflammatory and immunity-based actions involving activation of T cells, lymphocytes, and leukocytes, as well as cytokine–cytokine-receptor interaction, and chemokine signaling pathways.

Conclusion: The hub genes of COVID-19 helped to reveal the underlying pathogenesis and therapeutic targets of COVID-19. This study represents the first report on the molecular mechanism of MXYG decoction against COVID-19.

Keywords: TCM formulations, novel coronavirus, COVID-19, network pharmacology, molecular docking, molecular mechanism.

[1]
Guan, W.J.; Ni, Z.Y.; Hu, Y.; Liang, W.H.; Ou, C.Q.; He, J.X.; Liu, L.; Shan, H.; Lei, C.L.; Hui, D.S.C.; Du, B.; Li, L.J.; Zeng, G.; Yuen, K.Y.; Chen, R.C.; Tang, C.L.; Wang, T.; Chen, P.Y.; Xiang, J.; Li, S.Y.; Wang, J.L.; Liang, Z.J.; Peng, Y.X.; Wei, L.; Liu, Y.; Hu, Y.H.; Peng, P.; Wang, J.M.; Liu, J.Y.; Chen, Z.; Li, G.; Zheng, Z.J.; Qiu, S.Q.; Luo, J.; Ye, C.J.; Zhu, S.Y.; Zhong, N.S. China medical treatment expert group for covid-19. clinical characteristics of coronavirus disease 2019 in China. N. Engl. J. Med., 2020, 382(18), 1708-1720.
[http://dx.doi.org/10.1056/NEJMoa2002032] [PMID: 32109013]
[2]
Rubin, E.J.; Baden, L.R.; Morrissey, S.; Campion, E.W. Medical Journals and the 2019-nCoV Outbreak. N. Engl. J. Med., 2020, 382(9), 866-866.
[http://dx.doi.org/10.1056/NEJMe2001329] [PMID: 31986242]
[3]
The Lancet. Emerging understandings of 2019-nCoV. Lancet, 2020, 395(10221), 311-311.
[http://dx.doi.org/10.1016/S0140-6736(20)30186-0] [PMID: 31986259]
[4]
Huang, C.; Wang, Y.; Li, X.; Ren, L.; Zhao, J.; Hu, Y.; Zhang, L.; Fan, G.; Xu, J.; Gu, X.; Cheng, Z.; Yu, T.; Xia, J.; Wei, Y.; Wu, W.; Xie, X.; Yin, W.; Li, H.; Liu, M.; Xiao, Y.; Gao, H.; Guo, L.; Xie, J.; Wang, G.; Jiang, R.; Gao, Z.; Jin, Q.; Wang, J.; Cao, B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 2020, 395(10223), 497-506.
[http://dx.doi.org/10.1016/S0140-6736(20)30183-5] [PMID: 31986264]
[5]
NATCM. Diagnosis and treatment protocol for coronavirus pneumonia (Trial version 7) 2020.
[6]
Xia, J. Chinese medicine masters and academicians enter the national medical treatment expert group, and Chinese medicine deeply intervenes in the whole process of new coronary pneumonia diagnosis and treatment; China Youth Daily, 2020.
[7]
Wang, Z.; Chen, X.; Lu, Y.; Chen, F.; Zhang, W. Clinical characteristics and therapeutic procedure for four cases with 2019 novel coronavirus pneumonia receiving combined Chinese and Western medicine treatment. Biosci. Trends, 2020, 14(1), 64-68.
[http://dx.doi.org/10.5582/bst.2020.01030] [PMID: 32037389]
[8]
Ren, J.L.; Zhang, A.H.; Wang, X.J. Traditional Chinese medicine for COVID-19 treatment. Pharmacol. Res., 2020, 155104743
[http://dx.doi.org/10.1016/j.phrs.2020.104743] [PMID: 32145402]
[9]
Pengcao, W.; Qing, M.; Maorong, F.; Yanping, Z. Study of traditional Chinese medicine prescriptions on Treatment of cough caused by damp-heat. Chin. J. Tradit. Chin. Med. Pharm., 2010, 12(2), 1-4. [J]
[10]
Miao, Q.; Wei, P.C.; Fan, M.R.; Zhang, Y.P. Clinical study on treatment of cough variant asthma by Chinese medicine. Chin. J. Integr. Med., 2013, 19(7), 539-545.
[http://dx.doi.org/10.1007/s11655-013-1508-5] [PMID: 23818206]
[11]
Deng, W.; Zhang, B. A Comprehensive Analysis of the Guidelines for Diagnosis and Treatment of Novel Coronavirus in Different Provinces in China. J. Tradit. Chin. Med., 2020, 1113(2), 1-4.
[12]
Ling, C.Q. Traditional Chinese medicine is a resource for drug discovery against 2019 novel coronavirus (SARS-CoV-2). J. Integr. Med., 2020, 18(2), 87-88.
[http://dx.doi.org/10.1016/j.joim.2020.02.004] [PMID: 32122812]
[13]
Kibble, M.; Saarinen, N.; Tang, J.; Wennerberg, K.; Mäkelä, S.; Aittokallio, T. Network pharmacology applications to map the unexplored target space and therapeutic potential of natural products. Nat. Prod. Rep., 2015, 32(8), 1249-1266.
[http://dx.doi.org/10.1039/C5NP00005J] [PMID: 26030402]
[14]
Pei, L.; Shen, X.; Yan, Y.; Tan, C.; Qu, K.; Zou, J.; Wang, Y.; Ping, F. Virtual Screening of the multi-pathway and multi-gene regulatory molecular mechanism of Dachengqi decoction in the treatment of stroke Based on Network Pharmacology. Comb. Chem. High Throughput Screen., 2020, 23, 1-13.
[http://dx.doi.org/10.2174/1386207323666200311113747] [PMID: 32160845]
[15]
Ru, J.; Li, P.; Wang, J.; Zhou, W.; Li, B.; Huang, C.; Li, P.; Guo, Z.; Tao, W.; Yang, Y.; Xu, X.; Li, Y.; Wang, Y.; Yang, L. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J. Cheminform., 2014, 6, 13.
[http://dx.doi.org/10.1186/1758-2946-6-13] [PMID: 24735618]
[16]
Liu, Z.; Guo, F.; Wang, Y.; Li, C.; Zhang, X.; Li, H.; Diao, L.; Gu, J.; Wang, W.; Li, D.; He, F. BATMAN-TCM: a bioinformatics analysis tool for molecular mechanism of traditional chinese medicine. Sci. Rep., 2016, 6, 21146.
[http://dx.doi.org/10.1038/srep21146] [PMID: 26879404]
[17]
Zhang, W.; Chen, Y.; Jiang, H.; Yang, J.; Wang, Q.; Du, Y.; Xu, H. Integrated strategy for accurately screening biomarkers based on metabolomics coupled with network pharmacology. Talanta, 2020, 211120710
[http://dx.doi.org/10.1016/j.talanta.2020.120710] [PMID: 32070601]
[18]
Breuza, L.; Poux, S.; Estreicher, A.; Famiglietti, M.L.; Magrane, M.; Tognolli, M.; Bridge, A.; Baratin, D.; Redaschi, N. The UniProtKB guide to the human proteome. Database, 2016, 120, 1-10.
[http://dx.doi.org/10.1093/database/bav120]
[19]
Stelzer, G.; Rosen, N.; Plaschkes, I.; Zimmerman, S.; Twik, M.; Fishilevich, S.; Stein, T.I.; Nudel, R.; Lieder, I.; Mazor, Y.; Kaplan, S.; Dahary, D.; Warshawsky, D.; Guan-Golan, Y.; Kohn, A.; Rappaport, N.; Safran, M.; Lancet, D. The GeneCards Suite: from gene data mining to disease genome sequence analyses. Curr. Protoc. Bioinformatics, 2016, 54.
[20]
Amberger, J.S.; Bocchini, C.A.; Schiettecatte, F.; Scott, A.F.; Hamosh, A. OMIM.org: Online Mendelian Inheritance in Man (OMIM®), an online catalog of human genes and genetic disorders. Nucleic Acids Res., 2015, 43(Database issue), D789-D798.
[http://dx.doi.org/10.1093/nar/gku1205] [PMID: 25428349]
[21]
Szklarczyk, D.; Gable, A.L.; Lyon, D.; Junge, A.; Wyder, S.; Huerta-Cepas, J.; Simonovic, M.; Doncheva, N.T.; Morris, J.H.; Bork, P.; Jensen, L.J.; Mering, C.V. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res., 2019, 47(D1), D607-D613.
[http://dx.doi.org/10.1093/nar/gky1131] [PMID: 30476243]
[22]
Chin, C.H.; Chen, S.H.; Wu, H.H.; Ho, C.W.; Ko, M.T.; Lin, C.Y. ytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst. Biol., 2014, 8(Suppl. 4), S11.
[23]
Cattley, S.; Arthur, J.W. BioManager: the use of a bioinformatics web application as a teaching tool in undergraduate bioinformatics training. Brief. Bioinform., 2007, 8(6), 457-465.
[http://dx.doi.org/10.1093/bib/bbm039] [PMID: 17715151]
[24]
The Gene Ontology Consortium. Expansion of the Gene Ontology knowledgebase and resources. Nucleic Acids Res., 2017, 45(D1), D331-D338.
[http://dx.doi.org/10.1093/nar/gkw1108] [PMID: 27899567]
[25]
Kanehisa, M.; Furumichi, M.; Tanabe, M.; Sato, Y.; Morishima, K. KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res., 2017, 45(D1), D353-D361.
[http://dx.doi.org/10.1093/nar/gkw1092] [PMID: 27899662]
[26]
Ragunathan, A.; Malathi, K.; Ramaiah, S.; Anbarasu, A. FtsA as a cidal target for Staphylococcus aureus: Molecular docking and dynamics studies. J. Cell. Biochem., 2018, 120(5), 7751-7758.
[http://dx.doi.org/10.1002/jcb.28049] [PMID: 30417432]
[27]
Keskin, O.; Tuncbag, N.; Gursoy, A. Predicting protein-protein interactions from the molecular to the proteome level. Chem. Rev., 2016, 116(8), 4884-4909.
[http://dx.doi.org/10.1021/acs.chemrev.5b00683] [PMID: 27074302]
[28]
Baruah, V.; Bose, S. Immunoinformatics-aided identification of T cell and B cell epitopes in the surface glycoprotein of 2019-nCoV. J. Med. Virol., 2020, 92(5), 495-500.
[http://dx.doi.org/10.1002/jmv.25698] [PMID: 32022276]
[29]
Mehta, P.; McAuley, D.F.; Brown, M.; Sanchez, E.; Tattersall, R.S.; Manson, J.J. HLH Across Speciality Collaboration. UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet, 2020, 395(10229), 1033-1034.
[http://dx.doi.org/10.1016/S0140-6736(20)30628-0] [PMID: 32192578]
[30]
Li, G.; Fan, Y.; Lai, Y.; Han, T.; Li, Z.; Zhou, P.; Pan, P.; Wang, W.; Hu, D.; Liu, X.; Zhang, Q.; Wu, J. Coronavirus infections and immune responses. J. Med. Virol., 2020, 92(4), 424-432.
[http://dx.doi.org/10.1002/jmv.25685] [PMID: 31981224]
[31]
Okumura, A.; Pitha, P.M.; Yoshimura, A.; Harty, R.N. Interaction between Ebola virus glycoprotein and host toll-like receptor 4 leads to induction of proinflammatory cytokines and SOCS1. J. Virol., 2010, 84(1), 27-33.
[http://dx.doi.org/10.1128/JVI.01462-09] [PMID: 19846529]
[32]
Pauli, E.K.; Schmolke, M.; Wolff, T.; Viemann, D.; Roth, J.; Bode, J.G.; Ludwig, S. Influenza A virus inhibits type I IFN signaling via NF-kappaB-dependent induction of SOCS-3 expression. PLoS Pathog., 2008, 4(11)e1000196
[http://dx.doi.org/10.1371/journal.ppat.1000196] [PMID: 18989459]
[33]
Zhou, Y.; Fu, B.; Zheng, X.; Wang, D.; Zhao, C.; Qi, Y.; Sun, R.; Tian, Z.; Xu, X.; Wei, H. Aberrant pathogenic GM-CSF+ T cells and inflammatory CD14+ CD16+ monocytes in severe pulmonary syndrome patients of a new coronavirus. bioRxiv, 2020.
[34]
Chen, C.; Zhang, X.R.; Ju, Z.Y.; He, W.F. Advances in the research of cytokine storm mechanism induced by Corona Virus Disease 2019 and the corresponding immunotherapies. Zhonghua Shao Shang Za Zhi, 2020, 36E005
[35]
Qiu, R.; Wei, X.; Zhao, M.; Zhong, C.; Zhao, C.; Hu, J.; Li, M.; Huang, Y.; Han, S.; He, T. Outcome reporting from protocols of clinical trials of Coronavirus Disease 2019 (COVID-19): a review medRxiv, 2019.
[36]
Wang, Z.F.; Wang, Y.P.; Zhang, H.M.; Fan, Y.P.; Lü, C.; Wang, Y.Y. Thinking on Clinical rational use of TCM injection in the treatment of novel coronavirus pneumonia (COVID-19). Zhonghua Yi Xue Za Zhi, 2020, 100, E016-E016.
[PMID: 32122113]
[37]
Qi, F.; Qian, S.; Zhang, S.; Zhang, Z. Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochem. Biophys. Res. Commun., 2020, 526(1), 135-140.
[http://dx.doi.org/10.1016/j.bbrc.2020.03.044] [PMID: 32199615]
[38]
Cao, X. Self-regulation and cross-regulation of pattern-recognition receptor signalling in health and disease. Nat. Rev. Immunol., 2016, 16(1), 35-50.
[http://dx.doi.org/10.1038/nri.2015.8] [PMID: 26711677]
[39]
Chen, T.; Liu, H.X.; Yan, H.Y.; Wu, D.M.; Ping, J. Developmental origins of inflammatory and immune diseases. Mol. Hum. Reprod., 2016, 22(8), 858-865.
[http://dx.doi.org/10.1093/molehr/gaw036] [PMID: 27226490]
[40]
Kakizaki, M.; Watanabe, R. IL-10 expression in pyramidal neurons after neuropathogenic coronaviral infection. Neuropathology, 2017, 37(5), 398-406.
[http://dx.doi.org/10.1111/neup.12386] [PMID: 28493345]
[41]
Diemer, C.; Schneider, M.; Seebach, J.; Quaas, J.; Frösner, G.; Schätzl, H.M.; Gilch, S. Cell type-specific cleavage of nucleocapsid protein by effector caspases during SARS coronavirus infection. J. Mol. Biol., 2008, 376(1), 23-34.
[http://dx.doi.org/10.1016/j.jmb.2007.11.081] [PMID: 18155731]
[42]
Favreau, D.J.; Meessen-Pinard, M.; Desforges, M.; Talbot, P.J. Human coronavirus-induced neuronal programmed cell death is cyclophilin d dependent and potentially caspase dispensable. J. Virol., 2012, 86(1), 81-93.
[http://dx.doi.org/10.1128/JVI.06062-11] [PMID: 22013052]
[43]
Ren, L.; Yang, R.; Guo, L.; Qu, J.; Wang, J.; Hung, T. Apoptosis induced by the SARS-associated coronavirus in Vero cells is replication-dependent and involves caspase. DNA Cell Biol., 2005, 24(8), 496-502.
[http://dx.doi.org/10.1089/dna.2005.24.496] [PMID: 16101347]
[44]
Kindrachuk, J.; Ork, B.; Hart, B.J.; Mazur, S.; Holbrook, M.R.; Frieman, M.B.; Traynor, D.; Johnson, R.F.; Dyall, J.; Kuhn, J.H.; Olinger, G.G.; Hensley, L.E.; Jahrling, P.B. Antiviral potential of ERK/MAPK and PI3K/AKT/mTOR signaling modulation for Middle East respiratory syndrome coronavirus infection as identified by temporal kinome analysis. Antimicrob. Agents Chemother., 2015, 59(2), 1088-1099.
[http://dx.doi.org/10.1128/AAC.03659-14] [PMID: 25487801]
[45]
Joshi, S.D.; Dixit, S.R.; Kirankumar, M.N.; Aminabhavi, T.M.; Raju, K.V.S.N.; Narayan, R.; Lherbet, C.; Yang, K.S. Synthesis, antimycobacterial screening and ligand-based molecular docking studies on novel pyrrole derivatives bearing pyrazoline, isoxazole and phenyl thiourea moieties. Eur. J. Med. Chem., 2016, 107, 133-152.
[http://dx.doi.org/10.1016/j.ejmech.2015.10.047] [PMID: 26580979]
[46]
Sama, I.E.; Ravera, A.; Santema, B.T.; van Goor, H.; Ter Maaten, J.M.; Cleland, J.G.F.; Rienstra, M.; Friedrich, A.W.; Samani, N.J.; Ng, L.L.; Dickstein, K.; Lang, C.C.; Filippatos, G.; Anker, S.D.; Ponikowski, P.; Metra, M.; van Veldhuisen, D.J.; Voors, A.A. Circulating plasma concentrations of angiotensin-converting enzyme 2 in men and women with heart failure and effects of renin-angiotensin-aldosterone inhibitors. Eur. Heart J., 2020, 41(19), 1810-1817.
[http://dx.doi.org/10.1093/eurheartj/ehaa373] [PMID: 32388565]
[47]
Meng, J.; Xiao, G.; Zhang, J.; He, X.; Ou, M.; Bi, J.; Yang, R.; Di, W.; Wang, Z.; Li, Z.; Gao, H.; Liu, L.; Zhang, G. Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension. Emerg. Microbes Infect., 2020, 9(1), 757-760.
[http://dx.doi.org/10.1080/22221751.2020.1746200] [PMID: 32228222]
[48]
Zakaryan, H.; Arabyan, E.; Oo, A.; Zandi, K. Flavonoids: promising natural compounds against viral infections. Arch. Virol., 2017, 162(9), 2539-2551.
[http://dx.doi.org/10.1007/s00705-017-3417-y] [PMID: 28547385]
[49]
Perez-Vizcaino, F.; Fraga, C.G. Perez Vizcaino. Research trends in flavonoids and health. Arch. Biochem. Biophys., 2018, 646, 107-112.
[http://dx.doi.org/10.1016/j.abb.2018.03.022] [PMID: 29580946]
[50]
Chiow, K.H.; Phoon, M.C.; Putti, T.; Tan, B.K.; Chow, V.T. Evaluation of antiviral activities of Houttuynia cordata Thunb. extract, quercetin, quercetrin and cinanserin on murine coronavirus and dengue virus infection. Asian Pac. J. Trop. Med., 2016, 9(1), 1-7.
[http://dx.doi.org/10.1016/j.apjtm.2015.12.002] [PMID: 26851778]
[51]
Park, H.R.; Yoon, H.; Kim, M.K.; Lee, S.D.; Chong, Y. Synthesis and antiviral evaluation of 7-O-arylmethylquercetin derivatives against SARS-associated coronavirus (SCV) and hepatitis C virus (HCV). Arch. Pharm. Res., 2012, 35(1), 77-85.
[http://dx.doi.org/10.1007/s12272-012-0108-9] [PMID: 22297745]
[52]
Ryu, Y.B.; Jeong, H.J.; Kim, J.H.; Kim, Y.M.; Park, J.Y.; Kim, D.; Nguyen, T.T.; Park, S.J.; Chang, J.S.; Park, K.H.; Rho, M.C.; Lee, W.S. Biflavonoids from Torreya nucifera displaying SARS-CoV 3CL(pro) inhibition. Bioorg. Med. Chem., 2010, 18(22), 7940-7947.
[http://dx.doi.org/10.1016/j.bmc.2010.09.035] [PMID: 20934345]
[53]
Yao, Y.; Zhang, X.; Wang, Z.; Zheng, C.; Li, P.; Huang, C.; Tao, W.; Xiao, W.; Wang, Y.; Huang, L.; Yang, L. Deciphering the combination principles of Traditional Chinese Medicine from a systems pharmacology perspective based on Ma-huang Decoction. J. Ethnopharmacol., 2013, 150(2), 619-638.
[http://dx.doi.org/10.1016/j.jep.2013.09.018] [PMID: 24064232]
[54]
Kimura, M.; Kimura, I.; Guo, X.; Luo, B.; Kobayashi, S. Combined effects of Japanese-Sino medicine ‘Kakkon-to-ka-senkyu-shin’i’ and its related combinations and component drugs on adjuvant-induced inflammation in mice. Phytother. Res., 1992, 6(4), 209-216.
[http://dx.doi.org/10.1002/ptr.2650060409]
[55]
Jayaprakasam, B.; Yang, N.; Wen, M.C.; Wang, R.; Goldfarb, J.; Sampson, H.; Li, X.M. Constituents of the anti-asthma herbal formula ASHMI(TM) synergistically inhibit IL-4 and IL-5 secretion by murine Th2 memory cells, and eotaxin by human lung fibroblasts in vitro. J. Integr. Med., 2013, 11(3), 195-205.
[http://dx.doi.org/10.3736/jintegrmed2013029] [PMID: 23743163]
[56]
Yeh, Y.A.; Herenyiova, M.; Weber, G. Quercetin: synergistic action with carboxyamidotriazole in human breast carcinoma cells. Life Sci., 1995, 57(13), 1285-1292.
[http://dx.doi.org/10.1016/0024-3205(95)02085-W] [PMID: 7674820]
[57]
Son, H.U.; Yoon, E.K.; Yoo, C.Y.; Park, C.H.; Bae, M.A.; Kim, T.H.; Lee, C.H.; Lee, K.W.; Seo, H.; Kim, K.J.; Lee, S.H. Effects of Synergistic Inhibition on α-glucosidase by Phytoalexins in Soybeans. Biomolecules, 2019, 9(12)E828
[http://dx.doi.org/10.3390/biom9120828] [PMID: 31817312]
[58]
Das, N.; Berhow, M.A.; Angelino, D.; Jeffery, E.H. Camelina sativa defatted seed meal contains both alkyl sulfinyl glucosinolates and quercetin that synergize bioactivity. J. Agric. Food Chem., 2014, 62(33), 8385-8391.
[http://dx.doi.org/10.1021/jf501742h] [PMID: 25050614]
[59]
Pal, A.; Tripathi, A. Demonstration of bactericidal and synergistic activity of quercetin with meropenem among pathogenic carbapenem resistant Escherichia coli and Klebsiella pneumoniae. Microb. Pathog., 2020, 143104120
[http://dx.doi.org/10.1016/j.micpath.2020.104120] [PMID: 32169488]
[60]
Rakariyatham, K.; Wu, X.; Tang, Z.; Han, Y.; Wang, Q.; Xiao, H. Synergism between luteolin and sulforaphane in anti-inflammation. Food Funct., 2018, 9(10), 5115-5123.
[http://dx.doi.org/10.1039/C8FO01352G] [PMID: 30206627]
[61]
Williamson, E.M. Synergy and other interactions in phytomedicines. Phytomedicine, 2001, 8(5), 401-409.
[http://dx.doi.org/10.1078/0944-7113-00060] [PMID: 11695885]
[62]
Qin, C.; Zhou, L.; Hu, Z.; Zhang, S.; Yang, S.; Tao, Y.; Xie, C.; Ma, K.; Shang, K.; Wang, W.; Tian, D.S. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clin. Infect. Dis., 2020, 03(13), 248.
[http://dx.doi.org/10.1093/cid/ciaa248] [PMID: 32161940]

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