Background: The newly identified betacoronavirus SARS-CoV-2 is the causative pathogen of the 2019 coronavirus disease (COVID-19), which has killed more than 4.5 million people. SARS-CoV-2 causes severe respiratory distress syndrome by targeting the lungs and also induces myocardial damage. Shenshao Ningxin Yin (SNY) has been used for more than 700 years to treat influenza. Previous randomized controlled trials (RCTs) have demonstrated that SNY can improve the clinical symptoms of viral myocarditis, reverse arrhythmia, and reduce the level of myocardial damage markers. Methods: This work uses a rational computational strategy to identify existing drug molecules that target host pathways for the treatment of COVID-19 with myocarditis. Disease and drug targets were input into the STRING database to construct proteinɃprotein interaction networks. The Metascape database was used for GO and KEGG enrichment analysis. Results: SNY signaling modulated the pathways of coronavirus disease, including COVID-19, Ras signaling, viral myocarditis, and TNF signaling pathways. Tumor necrosis factor (TNF), cellular tumor antigen p53 (TP53), mitogen-activated protein kinase 1 (MAPK1), and the signal transducer and activator of transcription 3 (STAT3) were the pivotal targets of SNY. The components of SNY bound well with the pivotal targets, indicating there were potential biological activities. Conclusion: Our findings reveal the pharmacological role and molecular mechanism of SNY for the treatment of COVID-19 with myocarditis. We also, for the first time, demonstrate that SNY displays multi-component, multi-target, and multi-pathway characteristics with a complex mechanism of action.
Citation: Ze-Yu Zhang, Zhu-Jun Mao, Ye-ping Ruan, Xin Zhang. Computational identification of Shenshao Ningxin Yin as an effective treatment for novel coronavirus infection (COVID-19) with myocarditis[J]. Mathematical Biosciences and Engineering, 2022, 19(6): 5772-5792. doi: 10.3934/mbe.2022270
Background: The newly identified betacoronavirus SARS-CoV-2 is the causative pathogen of the 2019 coronavirus disease (COVID-19), which has killed more than 4.5 million people. SARS-CoV-2 causes severe respiratory distress syndrome by targeting the lungs and also induces myocardial damage. Shenshao Ningxin Yin (SNY) has been used for more than 700 years to treat influenza. Previous randomized controlled trials (RCTs) have demonstrated that SNY can improve the clinical symptoms of viral myocarditis, reverse arrhythmia, and reduce the level of myocardial damage markers. Methods: This work uses a rational computational strategy to identify existing drug molecules that target host pathways for the treatment of COVID-19 with myocarditis. Disease and drug targets were input into the STRING database to construct proteinɃprotein interaction networks. The Metascape database was used for GO and KEGG enrichment analysis. Results: SNY signaling modulated the pathways of coronavirus disease, including COVID-19, Ras signaling, viral myocarditis, and TNF signaling pathways. Tumor necrosis factor (TNF), cellular tumor antigen p53 (TP53), mitogen-activated protein kinase 1 (MAPK1), and the signal transducer and activator of transcription 3 (STAT3) were the pivotal targets of SNY. The components of SNY bound well with the pivotal targets, indicating there were potential biological activities. Conclusion: Our findings reveal the pharmacological role and molecular mechanism of SNY for the treatment of COVID-19 with myocarditis. We also, for the first time, demonstrate that SNY displays multi-component, multi-target, and multi-pathway characteristics with a complex mechanism of action.
| [1] |
N. Zhu, D. Zhang, W. Wang, X. Li, B. Yang, J. Song, et al., A novel coronavirus from patients with pneumonia in China, 2019, N. Engl. J. Med., 382 (2020), 727–733. https://doi.org/10.1056/NEJMoa2001017 doi: 10.1056/NEJMoa2001017
|
| [2] |
P. Zhou, X. L. Yang, X. G. Wang, B. Hu, L. Zhang, W. Zhang, et al., A pneumonia outbreak associated with a new coronavirus of probable bat origin, Nature, 579 (2020), 270–273. https://doi.org/10.1038/s41586-020-2012-7 doi: 10.1038/s41586-020-2012-7
|
| [3] |
S. Tian, Y. Xiong, H. Liu, L. Niu, J. Guo, M. Liao, et al., Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies, Mod. Pathol., 33 (2020), 1007–1014. https://doi.org/10.1038/s41379-020-0536-x doi: 10.1038/s41379-020-0536-x
|
| [4] |
Y. Xie, E. Xu, B. Bowe, Z. Al-Aly, Long-term cardiovascular outcomes of COVID-19, Nat. Med., 28 (2022), 583–590. https://doi.org/10.1038/s41591-022-01689-3 doi: 10.1038/s41591-022-01689-3
|
| [5] |
X. Chen, J. Tang, W. Xie, J. Wang, J. Jin, J. Ren, et al., Protective effect of the polysaccharide from Ophiopogon japonicus on streptozotocin-induced diabetic rats, Carbohydr. Polym., 94 (2013), 378–385. https://doi.org/10.1016/j.carbpol.2013.01.037 doi: 10.1016/j.carbpol.2013.01.037
|
| [6] |
Q. Qin, J. Niu, Z. Wang, W. Xu, Z. Qiao, Y. Gu, Astragalus embranaceus extract activates immune response in macrophages via heparanase, Molecules, 17 (2012), 7232–7240. https://doi.org/10.3390/molecules17067232 doi: 10.3390/molecules17067232
|
| [7] |
D. Meng, X. J. Chen, Y. Y. Bian, P. Li, D. Yang, J. N. Zhang, Effect of astragalosides on intracellular calcium overload in cultured cardiac myocytes of neonatal rats, Am. J. Chin. Med., 33 (2005), 11–20. https://doi.org/10.1142/S0192415X05002618. doi: 10.1142/S0192415X05002618
|
| [8] | Y. P. Wang, X. Y. Li, C. Q. Song, Z. B. Hu, Effect of astragaloside IV on T, B lymphocyte proliferation and peritoneal macrophage function in mice, Acta. Pharmacol. Sin., 23 (2002), 263–266. |
| [9] | X. Zhang, H. Q. Huangfu, H. J. Chen, Clinical research on modified Shenshao Ningxin Yin treating viral myocarditis of syndrome of deficiency of both Qi and Yin, Chin. Arch. Tradit. Chin. Med., 35 (2017), 319–322. |
| [10] |
H. L. Zuo, Y. C. Lin, H. Y. Huang, X. Wang, Y. Tang, Y. J. Hu, et al., The challenges andopportunities of traditional Chinese medicines against COVID-19: a way out from a network perspective, Acta Pharmacol. Sin., 42 (2021), 845–847. https://doi.org/10.1038/s41401-021-00645-0 doi: 10.1038/s41401-021-00645-0
|
| [11] |
T. Kaur, A. Madgulkar, M. Bhalekar, K. Asgaonkar, Molecular Docking in Formulationand Development, Curr. Drug Discovery Technol., 16 (2019), 30–39. https://doi.org/10.2174/1570163815666180219112421 doi: 10.2174/1570163815666180219112421
|
| [12] |
A. E. Lohning, S. M. Levonis, B. Williams-Noonan, S. S. Schweiker, A practical guide to molecular docking and homology modelling for medicinal chemists, Curr. Top. Med. Chem., 17 (2017), 2023–2040. https://doi.org/10.2174/1568026617666170130110827 doi: 10.2174/1568026617666170130110827
|
| [13] |
M. A. Yildirim, K. I. Goh, M. E. Cusick, A. L. Barabási, M. Vidal, Drug-target network, Nat. Biotechnol., 25 (2007), 1119–1126. https://doi.org/10.1038/nbt1338 doi: 10.1038/nbt1338
|
| [14] |
A. L. Hopkins, Network pharmacology: the next paradigm in drug discovery, Nat. Chem. Biol., 4 (2008), 682–690. https://doi.org/10.1038/nchembio.118 doi: 10.1038/nchembio.118
|
| [15] |
P. Zeng, X. M. Wang, C. Y. Ye, H. F. Su, Q. Tian, The main alkaloids in uncaria rhynchophylla and their antialzheimer's disease mechanism determined by a network pharmacology approach, Int. J. Mol. Sci., 22 (2021), 3612. https://doi.org/10.3390/ijms22073612 doi: 10.3390/ijms22073612
|
| [16] |
J. Xu, F. Wang, J. Guo, C. Xu, Y. Cao, Z. Fang, Q. Wang, Pharmacological mechanisms underlying the neuroprotective effects of alpinia oxyphylla miq. on Alzheimer's disease, Int. J. Mol. Sci., 21 (2020), 2071. https://doi.org/10.3390/ijms21062071 doi: 10.3390/ijms21062071
|
| [17] |
Y. Qiu, Z. J. Mao, Y. P. Ruan, X. Zhang, Exploration of the anti-insomnia mechanism of Ganoderma by central-peripheral multi-level interaction network analysis, BMC Microbiol., 21 (2021), 296. https://doi.org/10.1186/s12866-021-02361-5 doi: 10.1186/s12866-021-02361-5
|
| [18] |
J. Ru, P. Li, J. Wang, W. Zhou, B. Li, C. Huang, et al., TCMSP: a database of systems pharma-cology for drug discovery from herbal medicines, J. Cheminform., 6 (2014), 13. https://doi.org/10.1186/1758-2946-6-13 doi: 10.1186/1758-2946-6-13
|
| [19] |
M. V. Varma, R. S. Obach, C. Rotter, H. R. Miller, G. Chang, S. J. Steyn, et al., Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination, J. Med. Chem., 53 (2012), 1098–1108. https://doi.org/10.1021/jm901371v doi: 10.1021/jm901371v
|
| [20] |
X. Xu, W. Zhang, C. Huang, Y. Li, H. Yu, Y. Wang, et al., A novel chemometric method for the prediction of human oral bioavailability, Int. J. Mol. Sci., 13 (2012), 6964–6982. https://doi.org/10.3390/ijms13066964 doi: 10.3390/ijms13066964
|
| [21] |
W. Tao, X. Xu, X. Wang, B. Li, Y. Wang, Y. Li, et al., Network pharmacology-based prediction of the active ingredients and potential targets of Chinese herbal Radix Curcumae formula for application to cardiovascular disease, J. Ethnopharmacol., 145 (2013), 1–10. https://doi.org/10.1016/j.jep.2012.09.051 doi: 10.1016/j.jep.2012.09.051
|
| [22] |
H. Yang, W. Zhang, C. Huang, W. Zhou, Y. Yao, Z. Wang, et al., A novel systems pharmacology model for herbal medicine injection: a case using Reduning injection, BMC Complementary Altern. Med., 14 (2014), 430. https://doi.org/10.1186/1472-6882-14-430 doi: 10.1186/1472-6882-14-430
|
| [23] |
H. Y. Xu, Y. Q. Zhang, Z. M. Liu, T. Chen, C. Y. Lv, S. H. Tang, et al., ETCM: an encyclopaedia of traditional Chinese medicine, Nucleic Acids Res., 47 (2019), D976–D982. https://doi.org/10.1093/nar/gky987 doi: 10.1093/nar/gky987
|
| [24] |
D. S. Wishart, Y. D. Feunang, A. C. Guo, E. J. Lo, A. Marcu, J. R. Grant, et al., DrugBank 5.0: a major update to the DrugBank database for 2018, Nucleic Acids Res., 46 (2018), D1074–D1082. https://doi.org/10.1093/nar/gkx1037 doi: 10.1093/nar/gkx1037
|
| [25] |
U. Consortium, UniProt: the universal protein knowledgebase in 2021, Nucleic acids research, 49 (2021), D480–D489. https://doi.org/10.1093/nar/gkaa1100 doi: 10.1093/nar/gkaa1100
|
| [26] | M. Safran, I. Dalah, J. Alexander, N. Rosen, T. InyStein, M. Shmoish, et al., GeneCards Version 3: the human gene integrator, Database (Oxford), (2010), baq020. https://doi.org/10.1093/database/baq020 |
| [27] | J. S. Amberger, A. Hamosh, Searching online mendelian inheritance in man (omim): a knowledgebase of human genes and genetic phenotypes, Curr. Protoc. Bioinf., 58 (2017). https://doi.org/10.1002/cpbi.27 |
| [28] |
P. Shannon, A. Markiel, O. Ozier, N. S. Baliga, J. T. Wang, D. Ramage, et al., Cytoscape: a software environment for integrated models of biomolecular interaction networks, Genome Res., 13 (2003), 2498–2504. https://doi.org/10.1101/gr.1239303 doi: 10.1101/gr.1239303
|
| [29] |
D. Szklarczyk, A. L. Gable, K. C. Nastou, D. Lyon, R. Kirsch, S. Pyysalo, The STRING database in 2021: customizable protein-protein networks, and functional characterizationof user-uploaded gene/measurement sets, Nucleic Acids Res., 49 (2021), D605–D612. https://doi.org/10.1093/nar/gkaa1074 doi: 10.1093/nar/gkaa1074
|
| [30] |
S. K. Burley, C. Bhikadiya, C. Bi, S. Bittrich, L. Chen, G. V. Crichlow, et al., RCSB protein data bank: powerful new tools for exploring 3d structures of biological macromolecules for basic and applied research and education in fundamental biology, biomedicine, biotechnology, bioengineering and energy sciences, Nucleic Acids Res., 49 (2021), D437–D451. https://doi.org/10.1093/nar/gkaa1038 doi: 10.1093/nar/gkaa1038
|
| [31] |
S. Kim, J. Chen, T. Cheng, A. Gindulyte, J. He, S. He, et al., PubChem in 2021: new data content and improved web interfaces, Nucleic Acids Res., 49 (2021), D1388–D1395. https://doi.org/10.1093/nar/gkaa971 doi: 10.1093/nar/gkaa971
|
| [32] |
M. A. Crackower, R. Sarao, G. Y. Oudit, C. Yagil, I. Kozieradzki, S. E. Scanga, et al., Angiotensin-converting enzyme 2 is an essential regulator of heart function, Nature, 417 (2002), 822–828. https://doi.org/10.1038/nature00786 doi: 10.1038/nature00786
|
| [33] |
V. Monteil, H. Kwon, P. Prado, A. Hagelkrüys, R. A. Wimmer, M. Stahl, et al., Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2, Cells, 181 (2020), 905–913. https://doi.org/10.1016/j.cell.2020.04.004 doi: 10.1016/j.cell.2020.04.004
|
| [34] |
P. Towler, B. Staker, S. G. Prasad, S. Menon, J. Tang, T. Parsons, et al., ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysi, J. Biol. Chem., 279 (2004), 17996–18007. https://doi.org/10.1074/jbc doi: 10.1074/jbc
|
| [35] |
O. Trott, A. J. Olson, AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading, J. Comput. Chem., 31 (2010), 455–461. https://doi.org/10.1002/jcc.21334 doi: 10.1002/jcc.21334
|
| [36] |
Y. Zhou, B. Zhou, L. Pache, M. Chang, A. H. Khodabakhshi, O. Tanaseichuk, et al., Metascape provides a biologist-oriented resource for the analysis of systems-level datasets, Nat. Commun., 10 (2019), 152. https://doi.org/10.1038/s41467-019-09234-6 doi: 10.1038/s41467-019-09234-6
|
| [37] |
M. M. He, A. S. Smith, J. D. Oslob, W. M. Flanagan, A. C. Braisted, A. Whitty, et al., Small-molecule inhibition of TNF-alpha, Science, 310 (2005), 1022–1025. https://doi.org/10.1126/science.1116304 doi: 10.1126/science.1116304
|
| [38] |
G. Hoff, J. L. Avalos, K. Sens, C. Wolberger, Insights into the sirtuin mechanism from ternary complexes containing NAD(+) and acetylated peptide, Structure, 14 (2006), 1231–1240. https://doi.org/10.1016/j.str.2006.06.006 doi: 10.1016/j.str.2006.06.006
|
| [39] |
C. C. Milburn, M. Deak, S. M. Kelly, N. C. Price, D. R. Alessi, D. M. Van Aalten, Binding of phosphatidylinositol 3, 4, 5-trisphosphate to the pleckstrin homology domain of protein kinase B induces a conformational change, Biochem. J., 375 (2003), 531–538. https://doi.org/10.1042/bj20031229 doi: 10.1042/bj20031229
|
| [40] |
T. Kinoshita, H. Sugiyama, Y. Mori, N. Takahashi, A. Tomonaga, Identification of allosteric ERK2 inhibitors through in silico biased screening and competitive binding assay, Bioorg. Med. Chem. Lett., 26 (2016), 955–958. https://doi.org/10.1016/j.bmcl.2015.12.056 doi: 10.1016/j.bmcl.2015.12.056
|
| [41] |
P. Towler, B. Staker, S. G. Prasad, S. Menon, J. Tang, T. Parsons, et al., ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysi, J. Biol. Chem., 279 (2004), 17996–18007. https://doi.org/10.1074/jbc doi: 10.1074/jbc
|
| [42] |
X. Song, Y. Zhang, E. Dai, L. Wang, H. Du, Prediction of triptolide targets in rheumatoid arthritis using network pharmacology and molecular docking, Int. Immunopharmacol., 80 (2020), 106179. https://doi.org/10.1016/j.intimp.2019.106179 doi: 10.1016/j.intimp.2019.106179
|
| [43] |
G. H. Jian, B. Z. Su, W. J. Zhou, H. Xiong, Application of network pharmacology and molecular docking to elucidate the potential mechanism of Eucommia ulmoides-Radix Achyranthis Bidentatae against osteoarthritis, BioData. Min., 13 (2020), 12. https://doi.org/10.1186/s13040-020-00221-y doi: 10.1186/s13040-020-00221-y
|
| [44] |
M. Ye, G. Luo, D. Ye, M. She, N. Sun, Y. J. Lu, et al., Network pharmacology, molecular docking integrated surface plasmon resonance technology reveals the mechanism of Toujie Quwen Granules against coronavirus disease 2019 pneumonia, Phytomedicine., 85 (2021), 153401. https://doi.org/10.1016/j.phymed.2020.153401 doi: 10.1016/j.phymed.2020.153401
|
| [45] |
T. Wang, Z. Du, F. Zhu, Z. Cao, Y. An, Y. Gao, et al., Comorbidities and multi-organ injuries in the treatment of COVID-19, Lancet, 395 (2020), e52. https://doi.org/10.1016/S0140-6736(20)30558-4 doi: 10.1016/S0140-6736(20)30558-4
|
| [46] |
Q. Wu, L. Zhou, X. Sun, Z. Yan, C. Hu, J. Wu, et al., Altered lipid metabolism in recovered sars patients twelve years after infection, Sci. Rep., 7 (2017), 9110. https://doi.org/10.1038/s41598-017-09536-z doi: 10.1038/s41598-017-09536-z
|
| [47] |
K. Zhang, Is traditional Chinese medicine useful in the treatment of COVID-19?, Am. J. Emerg. Med., 38 (2020), 2238. https://doi.org/10.1016/j.ajem.2020.03.046 doi: 10.1016/j.ajem.2020.03.046
|
| [48] |
B. Yang, C. Y. Zheng, R. Zhang, C. Zhao, S. Li, Y. An, Quercetin efficiently alleviates TNF-α-stimulated injury by signal transducer and activator of transcription 1 and mitogen-activated protein kinase pathway in H9c2 cells: a protective role of quercetin in myocarditis, J. Cardiovasc. Pharm., 77 (2021), 570–577. https://doi.org/10.1097/FJC.0000000000001000 doi: 10.1097/FJC.0000000000001000
|
| [49] |
N. Abu-Elsaad, A. El-Karef, The falconoid luteolin mitigates the myocardial inflammatory response induced by high-carbohydrate/high-fat diet in wistar rats, Inflammation, 41 (2018), 221–231. https://doi.org/10.1007/s10753-017-0680-8 doi: 10.1007/s10753-017-0680-8
|
| [50] |
M. Zhou, H. Ren, J. Han, W. Wang, Q. Zheng, D. Wang, Protective effects of kaempferol against myocardial ischemia/reperfusion injury in isolated rat heart via antioxidant activity and inhibition of glycogen synthase kinase-3β, Oxid. Med. Cell. Longev., 2015 (2015), 481405. https://doi.org/10.1155/2015/481405 doi: 10.1155/2015/481405
|
| [51] |
L. Zhao, J. Han, J. Liu, K. Fan, T. Yuan, J. Han, et al., A novel formononetin derivative promotes anti-ischemic effects on acute ischemic injury in mice, Front. Inmicrobiol., 12 (2021), 786464. https://doi.org/10.3389/fmicb.2021.786464 doi: 10.3389/fmicb.2021.786464
|
| [52] |
D. W. Lee, R. Gardner, D. L. Porter, C. U. Louis, N. Ahmed, M. Jensen, et al., Current concepts in the diagnosis and management of cytokine release syndrome, Blood, 124 (2014), 188–195. https://doi.org/10.1182/blood-2014-05-552729 doi: 10.1182/blood-2014-05-552729
|
| [53] |
I. Komarowska, D. Coe, G. Wang, R. Haas, C. Mauro, M. Kishore, et al., Hepatocyte growth factor receptor c-met instructs T cell cardiotropism and promotes T cell migration to the heart via autocrine chemokine release, Immunity, 42 (2015), 1087–1099. https://doi.org/10.1016/j.immuni.2015.05.014 doi: 10.1016/j.immuni.2015.05.014
|
| [54] |
T. Liu, L. Zhang, D. Joo, S. C. Sun, NF-κB signaling in inflammation, Sig. Transduct. Target. Ther., 17023 (2017). https://doi.org/10.1038/sigtrans.2017.23 doi: 10.1038/sigtrans.2017.23
|
| [55] |
Z. Li, C. Wang, Y. Mao, J. Cui, X. Wang, J. Dang, et al., The expression of STAT3 inhibited the NF-ΚB signalling pathway and reduced inflammatory responses in mice with viral myocarditis, Int. Immunopharmacol., 95 (2021), 107534. https://doi.org/10.1016/j.intimp.2021.107534 doi: 10.1016/j.intimp.2021.107534
|
| [56] |
X. Xu, P. Chen, J. Wang, J. Feng, H. Zhou, X. Li, et al., Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for riskof human transmission, Sci. China Life Sci., 63 (2020), 457–460. https://doi.org/10.1007/s11427-020-1637-5 doi: 10.1007/s11427-020-1637-5
|
| [57] |
H. Zuo, R. Li, F. Ma, J. Jiang, K. Miao, H. Li, et al., Temporal echocardiography findings in patients with fulminant myocarditis: beyond ejection fraction decline, Front. Med., 14 (2020), 284–292. https://doi.org/10.1007/s11684-019-0713-9 doi: 10.1007/s11684-019-0713-9
|
| [58] |
P. Mehta, D. F. McAuley, M. Brown, E. Sanchez, R. S. Tattersall, J. J. Manson, et al., COVID-19: consider cytokine storm syndromes and immunosuppression, Lancet, 395 (2020), 1033–1034. https://doi.org/10.1016/S0140-6736(20)30628-0 doi: 10.1016/S0140-6736(20)30628-0
|
| [59] |
C. Huang, Y. Wang, X. Li, L. Ren, J. Zhao, Y. Hu, et al., Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, Lancet, 395 (2020), 497–506. https://doi.org/10.1016/S0140-6736(20)30183-5 doi: 10.1016/S0140-6736(20)30183-5
|
| [60] |
S. Shi, M. Qin, B. Shen, Y. Cai, T. Liu, F. Yang, et al., Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China, JAMA Cardiol., 5 (2020), 802–810. https://doi.org/10.1001/jamacardio.2020.0950 doi: 10.1001/jamacardio.2020.0950
|
| [61] |
Z. Varga, A. J. Flammer, P. Steiger, M. Haberecker, R. Andermatt, A. S. Zinkernagel, et al., Endothelial cell infection and endotheliitis in COVID-19, Lancet, 395 (2020), 1417–1418. https://doi.org/10.1016/S0140-6736(20)30937-5 doi: 10.1016/S0140-6736(20)30937-5
|
| [62] |
K. R. Menikdiwela, L. Ramalingam, F. Rasha, S. Wang, J. M. Dufour, N. S. Kalupahana, et al., Autophagy in metabolic syndrome: breaking the wheel by targeting the renin-angiotensin system, Cell Death Dis., 11 (2020), 87. https://doi.org/10.1038/s41419-020-2275-9 doi: 10.1038/s41419-020-2275-9
|
| [63] |
R. Lu, X. Zhao, J. Li, P. Niu, B. Yang, H. Wu, et al., Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding, Lancet, 395 (2020), 565–574. https://doi.org/10.1016/S0140-6736(20)30251-8 doi: 10.1016/S0140-6736(20)30251-8
|
| [64] |
X. Zou, K. Chen, J. Zou, P. Han, J. Hao, Z. Han, et al., Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection, Front. Med., 14 (2020), 185–192. https://doi.org/10.1007/s11684-020-0754-0 doi: 10.1007/s11684-020-0754-0
|
| [65] |
L. Chen, X. Li, M. Chen, Y. Feng, C. Xiong, The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2, Cardiovasc. Res., 116 (2020), 1097–1100. https://doi.org/10.1093/cvr/cvaa078 doi: 10.1093/cvr/cvaa078
|
 mbe-19-06-270 supplementary.docx |
 |
Figures(9) / Tables(2)
Ze-Yu Zhang, Zhu-Jun Mao, Ye-ping Ruan, Xin Zhang. Computational identification of Shenshao Ningxin Yin as an effective treatment for novel coronavirus infection (COVID-19) with myocarditis[J]. Mathematical Biosciences and Engineering, 2022, 19(6): 5772-5792. doi: 10.3934/mbe.2022270
DownLoad: