Combination of system biology to probe the anti-viral activity of andrographolide and its derivative against COVID-19

Khanal et al., RSC Advances, doi:10.1039/D0RA10529E

Dec 2021

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In Silico study showing that andrographolide and 14-deoxy-11,12-didehydroandrographolide from Andrographis paniculata modulate immune pathways and bind to SARS-CoV-2 papain-like protease, main protease, and spike protein. Authors find that both compounds regulate immune pathways including chemokine signaling, Rap1 signaling, and cytokine-cytokine receptor interaction. Molecular docking predicts that andrographolide binds more strongly than 14-deoxy-11,12-didehydroandrographolide to the viral proteins, with hydrogen bonding to key residues.

24 preclinical studies support the efficacy of andrographolide for COVID-19:

12 In Silico studies1-12

9 In Vitro studies1,13-20

3 In Vivo animal studies13,17,20

In Vitro studies demonstrate inhibition of the M^proA,17 protein. In Vitro studies demonstrate efficacy in Calu-3B,17, A549C,13, and HUVECD,17 cells. Animal studies demonstrate efficacy in Sprague Dawley miceE,17 and Golden Syrian hamstersF,13. Andrographolide inhibits M^pro in a dose-dependent manner17, reduces ACE2 levels in the lung tissue of mice in combination with baicalein17, inhibits binding between the SARS-CoV-2 spike protein and ACE217, alleviates lung inflammation and cytokine storm in mice17, and improves survival and reduces lung inflammation via anti-inflammatory effects in Syrian hamsters13.

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1. Zhang et al., Effects and Mechanisms of Andrographolide for COVID-19: A Network Pharmacology-Based and Experimentally Validated Study, Natural Product Communications, doi:10.1177/1934578X241288428.sagepub.com, doi.org.

2. Thomas et al., Cheminformatics approach to identify andrographolide derivatives as dual inhibitors of methyltransferases (nsp14 and nsp16) of SARS-CoV-2, Scientific Reports, doi:10.1038/s41598-024-58532-7.nature.com, doi.org.

3. Bhattarai et al., Investigating the binding affinity of andrographolide against human SARS-CoV-2 spike receptor-binding domain through docking and molecular dynamics simulations, Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2023.2174596.tandfonline.com, doi.org.

4. Nguyen et al., The Potential of Ameliorating COVID-19 and Sequelae From Andrographis paniculata via Bioinformatics, Bioinformatics and Biology Insights, doi:10.1177/11779322221149622.sagepub.com, doi.org.

5. Dassanayake et al., Molecular Docking and In-Silico Analysis of Natural Biomolecules against Dengue, Ebola, Zika, SARS-CoV-2 Variants of Concern and Monkeypox Virus, International Journal of Molecular Sciences, doi:10.3390/ijms231911131.mdpi.com, doi.org.

6. Ningrum et al., Potency Of Andrographolide, L-Mimosine And Asiaticoside Compound As Antiviral For Covid-19 Based On In Silico Method, Proceedings Universitas Muhammadiyah Yogyakarta Undergraduate Conference, doi:10.18196/umygrace.v2i2.418.ac.id, doi.org.

7. Ravichandran et al., Identification of Potential Semisynthetic Andrographolide Derivatives to Combat COVID-19 by Targeting the SARS-COV-2 Spike Protein and Human ACE2 Receptor– An In-silico Approach, Biointerface Research in Applied Chemistry, doi:10.33263/BRIAC132.155.biointerfaceresearch.com, doi.org.

8. Saeheng et al., In Silico Prediction of Andrographolide Dosage Regimens for COVID-19 Treatment, The American Journal of Chinese Medicine, doi:10.1142/S0192415X22500732.worldscientific.com, doi.org.

9. Khanal et al., Combination of system biology to probe the anti-viral activity of andrographolide and its derivative against COVID-19, RSC Advances, doi:10.1039/D0RA10529E.rsc.org, doi.org.

10. Rehan et al., A Computational Approach Identified Andrographolide as a Potential Drug for Suppressing COVID-19-Induced Cytokine Storm, Frontiers in Immunology, doi:10.3389/fimmu.2021.648250.frontiersin.org, doi.org.

11. Rajagopal et al., Activity of phytochemical constituents of Curcuma longa (turmeric) and Andrographis paniculata against coronavirus (COVID-19): an in silico approach, Future Journal of Pharmaceutical Sciences, doi:10.1186/s43094-020-00126-x.springeropen.com, doi.org.

12. Dey et al., The role of andrographolide and its derivative in COVID-19 associated proteins and immune system, Research Square, doi:10.21203/rs.3.rs-35800/v1.researchsquare.com, doi.org.

13. Kongsomros et al., In vivo evaluation of Andrographis paniculata and Boesenbergia rotunda extract activity against SARS-CoV-2 Delta variant in Golden Syrian hamsters: Potential herbal alternative for COVID-19 treatment, Journal of Traditional and Complementary Medicine, doi:10.1016/j.jtcme.2024.05.004.sciencedirect.com, doi.org.

14. Chaopreecha et al., Andrographolide attenuates SARS-CoV-2 infection via an up-regulation of glutamate-cysteine ligase catalytic subunit (GCLC), Phytomedicine, doi:10.1016/j.phymed.2024.156279.sciencedirect.com, doi.org.

15. Li et al., Andrographolide suppresses SARS-CoV-2 infection by downregulating ACE2 expression: A mechanistic study, Antiviral Therapy, doi:10.1177/13596535241259952.sagepub.com, doi.org.

16. Low et al., The wide spectrum anti-inflammatory activity of andrographolide in comparison to NSAIDs: a promising therapeutic compound against the cytokine storm, bioRxiv, doi:10.1101/2024.02.21.581396.biorxiv.org, doi.org.

17. Wan et al., Synergistic inhibition effects of andrographolide and baicalin on coronavirus mechanisms by downregulation of ACE2 protein level, Scientific Reports, doi:10.1038/s41598-024-54722-5.nature.com, doi.org.

18. Siridechakorn et al., Inhibitory efficiency of Andrographis paniculata extract on viral multiplication and nitric oxide production, Scientific Reports, doi:10.1038/s41598-023-46249-y.nature.com, doi.org.

19. Mohd Abd Razak et al., In Vitro Anti-SARS-CoV-2 Activities of Curcumin and Selected Phenolic Compounds, Natural Product Communications, doi:10.1177/1934578X231188861.sagepub.com, doi.org.

20. Pu et al., The effects and mechanisms of the anti-COVID-19 traditional Chinese medicine, Dehydroandrographolide from Andrographis paniculata (Burm.f.) Wall, on acute lung injury by the inhibition of NLRP3-mediated pyroptosis, Phytomedicine, doi:10.1016/j.phymed.2023.154753.sciencedirect.com, doi.org.

a. The main protease or M^pro, also known as 3CL^pro or nsp5, is a cysteine protease that cleaves viral polyproteins into functional units needed for replication. Inhibiting M^pro disrupts the SARS-CoV-2 lifecycle within the host cell, preventing the creation of new copies.

b. Calu-3 is a human lung adenocarcinoma cell line with moderate ACE2 and TMPRSS2 expression and SARS-CoV-2 susceptibility. It provides a model of the human respiratory epithelium, but many not be ideal for modeling early stages of infection due to the moderate expression levels of ACE2 and TMPRSS2.

c. A549 is a human lung carcinoma cell line with low ACE2 expression and SARS-CoV-2 susceptibility. Viral entry/replication can be studied but the cells may not replicate all aspects of lung infection.

d. HUVEC (Human Umbilical Vein Endothelial Cells) are primary endothelial cells derived from the vein of the umbilical cord. They are used to study vascular biology, including inflammation, angiogenesis, and viral interactions with endothelial cells.

e. An outbred multipurpose breed of albino mouse used extensively in medical research.

f. A rodent model widely used in infectious disease research due to their susceptibility to viral infections and similar disease progression to humans.

Khanal et al., 31 Dec 2021, peer-reviewed, 9 authors. Contact: manish.nriashrd@gmail.com, shailendra.gurav@nic.in.

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

This Paper Andrographol..All

Combination of system biology to probe the anti-viral activity of andrographolide and its derivative against COVID-19

Pukar Khanal, Yadu Nandan Dey, Rajesh Patil, Rupesh Chikhale, Manish M Wanjari, Shailendra S Gurav, B M Patil, Bhavana Srivastava, Sudesh N Gaidhani

RSC Advances, doi:10.1039/d0ra10529e

The present study aimed to investigate the binding affinity of andrographolide and its derivative i.e., 14deoxy-11,12-didehydroandrographolide with targets related to COVID-19 and their probable role in regulating multiple pathways in COVID-19 infection. SMILES of both compounds were retrieved from the PubChem database and predicted for probably regulated proteins. The predicted proteins were queried in STRING to evaluate the protein-protein interaction, and modulated pathways were identified concerning the KEGG database. Drug-likeness and ADMET profile of each compound was evaluated using MolSoft and admetSAR 2.0, respectively. Molecular docking was carried using Autodock 4.0. Andrographolide and its derivative were predicted to have a high binding affinity with papain-like protease, coronavirus main proteinase, and spike protein. Molecular dynamics simulation studies were performed for each complex which suggested the strong binding affinities of both compounds with targets. Network pharmacology analysis revealed that both compounds modulated the immune system by regulating chemokine signaling, Rap1 signaling, cytokine-cytokine receptor interaction, MAPK signaling, NF-kappa B signaling, RAS signaling, p53 signaling, HIF-1 signaling, and natural killer cellmediated cytotoxicity. The study suggests strong interaction of andrographolide and 14-deoxy-11,12didehydroandrographolide against COVID-19 associated target proteins and exhibited different immunoregulatory pathways.

Author contributions MMW and BMP: conceptualization, supervision, investigation; RVC and RBP: molecular docking and dynamics studies; PK and YDD: network pharmacology and analysis; SNG and BV: methodology, soware data analysis; SSG and RBP: writing-original dra preparation; MMW and SSG: formal analysis, visualization, reviewing and editing. Ethical statement This study doesn't include any animal or human study. Conflicts of interest The authors declare no competing interests.

References

Bahmani, Saki, Shahsavari, Raeian-Kopaei, Sepahvand et al., Asian Pac, J. Trop. Biomed

Cai, Chen, Li, Zhang, Zhou et al., None, Antiviral Res

Cai, Li, Chen, Wang, Zhang et al., None, Antiviral Res

Cai, Wen, Zhou, Wu, Chen et al., None, Antiviral Res

Case, Betz, Cerutti, Cheatham, Darden et al., AMBER 2016

Chen, Michaelis, Hsu, Tsai, Yang et al., None, J. Ethnopharmacol

Chen, Xue, Ye, Fang, Liu et al., None, Biol. Pharm. Bull

Chi, Flavell, MAP Kinase Signaling Protocols

Chikhale, Gurav, Patil, Sinha, Prasad et al., None, J. Biomol. Struct. Dyn

Chikhale, Pant, Menghani, Khedekar, None, BMC Infect. Dis, doi:10.1186/1471-2334-14-S3-E24

Chikhale, Sinha, Patil, Prasad, Shakya et al., None, J. Biomol. Struct. Dyn

Chikhale, Sinha, Wanjari, Gurav, Ayyanar et al., None, Mol. Divers, doi:10.1007/s11030-021-10183-w

Edwin, Vasantha-Srinivasan, Senthil-Nathan, Thanigaivel, Ponsankar et al., None, Acta Trop

Enmozhi, Raja, Sebastine, Joseph, None, J. Biomol. Struct. Dyn

Ferraz, Gomes, Novaes, Goulart Trossini, None, Future Med. Chem

Gentile, Patamia, Scala, Sciortino, Piperno et al., None, Mar. Drugs

Ghosh, Brindisi, Shahabi, Chapman, Mesecar, None, ChemMedChem

Gupta, Mishra, Ganju, None, Arch. Virol

Hagar, Ahmed, Aljohani, Alhaddad, None, Int. J. Mol. Sci

Huang, Wang, Li, Ren, Zhao et al., None, Lancet

Kerzare, Chikhale, Bansode, Amnerkar, Karodia et al., None, J. Braz. Chem. Soc

Khanal, Chikhale, Dey, Pasha, Chand et al., None, J. Biomol. Struct. Dyn

Khanal, Patil, Chand, Naaz, None, Nat. Prod. Bioprospect

Kortlever, Sodir, Wilson, Burkhart, Pellegrinet et al., None, Cell

Lagunin, Ivanov, Rudik, Filimonov, Poroikov, None, Bioinformatics

Lee, Tseng, Young, Sun, Wang et al., None, Br. J. Pharmacol

Lin, Chen, Duh, Chang, Liu, None, Biol. Pharm. Bull

Lin, Tsai, Tsai, Lai, Wan et al., None, Antiviral Res

Magrone, Magrone, Jirillo, None, Endocr. Metab. Immune Disord. -Drug Targets

Mahady, None, Curr. Pharm. Des

Mishra, Dash, Dey, None, J. Trop. Med

Mopuri, Ganjayi, Banavathy, Parim, Meriga, None, BMC Complementary Altern. Med

Morris, Huey, Lindstrom, Sanner, Belew et al., None, J. Comput. Chem

Ngo, Quynh Anh, Pham, Thi Le, Pham et al., None, J. Chem. Inf. Model

Of, the International, Nat. Microbiol

Olubiyi, Olagunju, Keutmann, Loschwitz, Strodel, None, Molecules

Opitz, Van Laak, Eitel, Suttorp, None, Am. J. Respir. Crit. Care Med

Patil, Chikhale, Khanal, Gurav, Ayyanar et al., None, Inform. Med. Unlocked

Pongtuluran, Rofaani, None, HAYATI J. Biosci

Puri, Saxena, Saxena, Saxena, Srivastava et al., None, J. Nat. Prod

Ryu, Jeong, Kim, Kim, Park et al., None, Bioorg. Med. Chem

Schwede, Kopp, Guex, Peitsch, None, Nucleic Acids Res

Seniya, Shrivastava, Singh, Khan, None, Asian Pac. J. Trop. Dis

Shahinshavali, Hossain, Kumar, Reddy, Kolli et al., None, Tetrahedron Lett

Sinha, Prasad, Islam, Gurav, Patil et al., None, J. Biomol. Struct. Dyn

Sinha, Shakya, Prasad, Singh, Gurav et al., None, J. Biomol. Struct. Dyn

Sofowora, Ogunbodede, Onayade, None, Afr. J. Tradit. Complement. Altern. Med

Sokol, Luster, None, Cold Spring Harb. Perspect. Biol

Szklarczyk, Morris, Cook, Kuhn, Wyder et al., None, Nucleic Acids Res

Wan, Yi, Fan, Lv, Zhang et al., None, MedRxiv

Wang, Hu, Hu, Zhu, Liu et al., None, Jama

Wang, Wang, Dong, Liu, Italiani et al., None, Acta Pharmacol. Sin

Wang, Wang, Kollman, Case, None, J. Am. Chem. Soc

Wen, Shyur, Jan, Liang, Kuo et al., None, J. Tradit. Complement. Med

Wiart, Kumar, Yusof, Hamimah, Fauzi et al., None, Phytother Res

Wintachai, Lee, Ramphan, Kuadkitkan, Wikan et al., None, Sci. Rep

Xu, Shi, Wang, Zhang, Huang et al., None, Lancet Respir. Med

Yang, Lou, Sun, Li, Cai et al., None, Bioinformatics

Zhang, Lin, Sun, Curth, Drosten et al., None, Science

Zhang, Tan, None, Acta Pharmacol. Sin

Zhu, Zhang, Wang, Li, Yang et al., None, N. Engl. J. Med

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Engl. J. Med.", "key": "D0RA10529E-(cit1)/*[position()=1]", "volume": "382", "year": "2020" }, { "DOI": "10.1038/s41564-020-0695-z", "author": "of the International", "doi-asserted-by": "crossref", "first-page": "536", "journal-title": "Nat. Microbiol.", "key": "D0RA10529E-(cit2)/*[position()=1]", "volume": "5", "year": "2020" }, { "DOI": "10.1080/07391102.2020.1762741", "author": "Sinha", "doi-asserted-by": "crossref", "first-page": "1", "journal-title": "J. Biomol. Struct. Dyn.", "key": "D0RA10529E-(cit3)/*[position()=1]", "year": "2020" }, { "DOI": "10.1164/rccm.200909-1427SO", "author": "Opitz", "doi-asserted-by": "crossref", "first-page": "1294", "journal-title": "Am. J. Respir. Crit. Care Med.", "key": "D0RA10529E-(cit4)/*[position()=1]", "volume": "181", "year": "2010" }, { "DOI": "10.1016/S0140-6736(20)30183-5", "author": "Huang", "doi-asserted-by": "crossref", "first-page": "497", "journal-title": "Lancet", "key": "D0RA10529E-(cit5)/*[position()=1]", "volume": "395", "year": "2020" }, { "DOI": "10.1001/jama.2020.1585", "author": "Wang", "doi-asserted-by": "crossref", "first-page": "1061", "journal-title": "Jama", "key": "D0RA10529E-(cit6)/*[position()=1]", "volume": "323", "year": "2020" }, { "author": "Wan", "first-page": "1", "journal-title": "MedRxiv", "key": "D0RA10529E-(cit7)/*[position()=1]", "year": "2020" }, { "DOI": "10.1016/S2213-2600(20)30076-X", "author": "Xu", "doi-asserted-by": "crossref", "first-page": "420", "journal-title": "Lancet Respir. Med.", "key": "D0RA10529E-(cit8)/*[position()=1]", "volume": "8", "year": "2020" }, { "author": "Zhang", "first-page": "1157", "journal-title": "Acta Pharmacol. Sin.", "key": "D0RA10529E-(cit9)/*[position()=1]", "volume": "21", "year": "2000" }, { "DOI": "10.1080/07391102.2020.1869588", "author": "Khanal", "doi-asserted-by": "crossref", "first-page": "1", "journal-title": "J. Biomol. Struct. Dyn.", "key": "D0RA10529E-(cit10)/*[position()=1]", "year": "2021" }, { "DOI": "10.1007/s13659-020-00260-2", "author": "Khanal", "doi-asserted-by": "crossref", "first-page": "325", "journal-title": "Nat. Prod. Bioprospect.", "key": "D0RA10529E-(cit11)/*[position()=1]", "volume": "10", "year": "2020" }, { "DOI": "10.1016/S2225-4110(16)30055-4", "author": "Wen", "doi-asserted-by": "crossref", "first-page": "41", "journal-title": "J. Tradit. Complement. Med.", "key": "D0RA10529E-(cit12)/*[position()=1]", "volume": "1", "year": "2011" }, { "DOI": "10.1016/j.jep.2008.07.048", "author": "Chen", "doi-asserted-by": "crossref", "first-page": "108", "journal-title": "J. Ethnopharmacol.", "key": "D0RA10529E-(cit13)/*[position()=1]", "volume": "120", "year": "2008" }, { "DOI": "10.1248/bpb.31.2018", "author": "Lin", "doi-asserted-by": "crossref", "first-page": "2018", "journal-title": "Biol. Pharm. Bull.", "key": "D0RA10529E-(cit14)/*[position()=1]", "volume": "31", "year": "2008" }, { "DOI": "10.1016/j.bmc.2010.09.035", "author": "Ryu", "doi-asserted-by": "crossref", "first-page": "7940", "journal-title": "Bioorg. Med. Chem.", "key": "D0RA10529E-(cit15)/*[position()=1]", "volume": "18", "year": "2010" }, { "author": "Chikhale", "first-page": "1", "journal-title": "J. Biomol. Struct. Dyn.", "key": "D0RA10529E-(cit16)/*[position()=1]", "year": "2020" }, { "author": "Chikhale", "first-page": "1", "journal-title": "J. Biomol. Struct. Dyn.", "key": "D0RA10529E-(cit17)/*[position()=1]", "year": "2020" }, { "DOI": "10.1080/07391102.2020.1762741", "author": "Sinha", "doi-asserted-by": "crossref", "first-page": "1", "journal-title": "J. Biomol. Struct. Dyn.", "key": "D0RA10529E-(cit18)/*[position()=1]", "year": "2020" }, { "DOI": "10.1007/s11030-021-10183-w", "author": "Chikhale", "doi-asserted-by": "publisher", "journal-title": "Mol. Divers.", "key": "D0RA10529E-(cit19)/*[position()=1]", "year": "2021" }, { "author": "Patil", "first-page": "100504", "journal-title": "Inform. Med. Unlocked", "key": "D0RA10529E-(cit20)/*[position()=1]", "year": "2020" }, { "DOI": "10.2174/1381612054367481", "author": "Mahady", "doi-asserted-by": "crossref", "first-page": "2405", "journal-title": "Curr. Pharm. Des.", "key": "D0RA10529E-(cit21)/*[position()=1]", "volume": "11", "year": "2005" }, { "author": "Sofowora", "first-page": "210", "journal-title": "Afr. J. Tradit. Complement. Altern. Med.", "key": "D0RA10529E-(cit22)/*[position()=1]", "volume": "10", "year": "2013" }, { "DOI": "10.1016/j.apjtb.2015.06.004", "author": "Bahmani", "doi-asserted-by": "crossref", "first-page": "858", "journal-title": "Asian Pac. J. Trop. Biomed.", "key": "D0RA10529E-(cit23)/*[position()=1]", "volume": "5", "year": "2015" }, { "DOI": "10.1038/srep14179", "author": "Wintachai", "doi-asserted-by": "crossref", "first-page": "14179", "journal-title": "Sci. Rep.", "key": "D0RA10529E-(cit24)/*[position()=1]", "volume": "5", "year": "2015" }, { "DOI": "10.4308/hjb.22.2.67", "author": "Pongtuluran", "doi-asserted-by": "crossref", "first-page": "67", "journal-title": "HAYATI J. Biosci.", "key": "D0RA10529E-(cit25)/*[position()=1]", "volume": "22", "year": "2015" }, { "DOI": "10.1186/s12906-015-0598-3", "author": "Mopuri", "doi-asserted-by": "crossref", "first-page": "76", "journal-title": "BMC Complementary Altern. Med.", "key": "D0RA10529E-(cit26)/*[position()=1]", "volume": "15", "year": "2015" }, { "DOI": "10.1021/np50097a002", "author": "Puri", "doi-asserted-by": "crossref", "first-page": "995", "journal-title": "J. Nat. Prod.", "key": "D0RA10529E-(cit27)/*[position()=1]", "volume": "56", "year": "1993" }, { "DOI": "10.1155/2011/579518", "author": "Mishra", "doi-asserted-by": "crossref", "first-page": "579518", "journal-title": "J. Trop. Med.", "key": "D0RA10529E-(cit28)/*[position()=1]", "volume": "2011", "year": "2011" }, { "DOI": "10.1038/aps.2009.205", "author": "Wang", "doi-asserted-by": "crossref", "first-page": "191", "journal-title": "Acta Pharmacol. Sin.", "key": "D0RA10529E-(cit29)/*[position()=1]", "volume": "31", "year": "2010" }, { "DOI": "10.1007/s00705-016-3166-3", "author": "Gupta", "doi-asserted-by": "crossref", "first-page": "611", "journal-title": "Arch. Virol.", "key": "D0RA10529E-(cit30)/*[position()=1]", "volume": "162", "year": "2017" }, { "DOI": "10.1016/j.actatropica.2016.07.009", "author": "Edwin", "doi-asserted-by": "crossref", "first-page": "167", "journal-title": "Acta Trop.", "key": "D0RA10529E-(cit31)/*[position()=1]", "volume": "163", "year": "2016" }, { "DOI": "10.1016/S2222-1808(14)60692-7", "author": "Seniya", "doi-asserted-by": "crossref", "first-page": "S624", "journal-title": "Asian Pac. J. Trop. Dis.", "key": "D0RA10529E-(cit32)/*[position()=1]", "volume": "4", "year": "2014" }, { "DOI": "10.1111/bph.12440", "author": "Lee", "doi-asserted-by": "crossref", "first-page": "237", "journal-title": "Br. J. Pharmacol.", "key": "D0RA10529E-(cit33)/*[position()=1]", "volume": "171", "year": "2014" }, { "DOI": "10.1248/bpb.32.1385", "author": "Chen", "doi-asserted-by": "crossref", "first-page": "1385", "journal-title": "Biol. Pharm. Bull.", "key": "D0RA10529E-(cit34)/*[position()=1]", "volume": "32", "year": "2009" }, { "DOI": "10.1016/j.antiviral.2005.07.002", "author": "Lin", "doi-asserted-by": "crossref", "first-page": "36", "journal-title": "Antiviral Res.", "key": "D0RA10529E-(cit35)/*[position()=1]", "volume": "68", "year": "2005" }, { "DOI": "10.1002/ptr.1765", "author": "Wiart", "doi-asserted-by": "crossref", "first-page": "1069", "journal-title": "Phytother Res.", "key": "D0RA10529E-(cit36)/*[position()=1]", "volume": "19", "year": "2005" }, { "DOI": "10.1016/j.antiviral.2016.07.020", "author": "Cai", "doi-asserted-by": "crossref", "first-page": "95", "journal-title": "Antiviral Res.", "key": "D0RA10529E-(cit37)/*[position()=1]", "volume": "133", "year": "2016" }, { "DOI": "10.1016/j.antiviral.2015.03.008", "author": "Cai", "doi-asserted-by": "crossref", "first-page": "82", "journal-title": "Antiviral Res.", "key": "D0RA10529E-(cit38)/*[position()=1]", "volume": "118", "year": "2015" }, { "DOI": "10.1016/j.antiviral.2020.104885", "author": "Cai", "doi-asserted-by": "crossref", "first-page": "104885", "journal-title": "Antiviral Res.", "key": "D0RA10529E-(cit39)/*[position()=1]", "volume": "181", "year": "2020" }, { "DOI": "10.1080/07391102.2020.1760136", "author": "Enmozhi", "doi-asserted-by": "crossref", "first-page": "1", "journal-title": "J. Biomol. Struct. Dyn.", "key": "D0RA10529E-(cit40)/*[position()=1]", "year": "2020" }, { "DOI": "10.1002/cmdc.202000223", "author": "Ghosh", "doi-asserted-by": "crossref", "first-page": "907", "journal-title": "ChemMedChem", "key": "D0RA10529E-(cit41)/*[position()=1]", "volume": "15", "year": "2020" }, { "DOI": "10.1021/acs.jcim.0c00491", "author": "Ngo", "doi-asserted-by": "crossref", "first-page": "5771", "issue": "12", "journal-title": "J. Chem. Inf. Model.", "key": "D0RA10529E-(cit42)/*[position()=1]", "volume": "60", "year": "2020" }, { "DOI": "10.3390/ijms21113922", "author": "Hagar", "doi-asserted-by": "crossref", "first-page": "3922", "journal-title": "Int. J. Mol. Sci.", "key": "D0RA10529E-(cit43)/*[position()=1]", "volume": "21", "year": "2020" }, { "DOI": "10.3390/molecules25143193", "author": "Olubiyi", "doi-asserted-by": "crossref", "first-page": "3193", "journal-title": "Molecules", "key": "D0RA10529E-(cit44)/*[position()=1]", "volume": "25", "year": "2020" }, { "DOI": "10.4155/fmc-2020-0165", "author": "Ferraz", "doi-asserted-by": "crossref", "first-page": "1815", "journal-title": "Future Med. Chem.", "key": "D0RA10529E-(cit45)/*[position()=1]", "volume": "12", "year": "2020" }, { "DOI": "10.3390/md18040225", "author": "Gentile", "doi-asserted-by": "crossref", "first-page": "225", "journal-title": "Mar. Drugs", "key": "D0RA10529E-(cit46)/*[position()=1]", "volume": "18", "year": "2020" }, { "DOI": "10.1126/science.abb3405", "author": "Zhang", "doi-asserted-by": "crossref", "first-page": "409", "journal-title": "Science", "key": "D0RA10529E-(cit47)/*[position()=1]", "volume": "368", "year": "2020" }, { "DOI": "10.1016/j.tetlet.2020.152336", "author": "Shahinshavali", "doi-asserted-by": "crossref", "first-page": "152336", "journal-title": "Tetrahedron Lett.", "key": "D0RA10529E-(cit48)/*[position()=1]", "volume": "61", "year": "2020" }, { "key": "D0RA10529E-(cit49)/*[position()=1]", "unstructured": "Available from: https://pubchem.ncbi.nlm.nih.gov/ , (accessed November 17, 2020)" }, { "DOI": "10.1093/bioinformatics/btt322", "author": "Lagunin", "doi-asserted-by": "crossref", "first-page": "2062", "journal-title": "Bioinformatics", "key": "D0RA10529E-(cit50)/*[position()=1]", "volume": "29", "year": "2013" }, { "DOI": "10.1093/nar/gkw937", "author": "Szklarczyk", "doi-asserted-by": "crossref", "first-page": "D362", "journal-title": "Nucleic Acids Res.", "key": "D0RA10529E-(cit51)/*[position()=1]", "volume": "45", "year": "2017" }, { "key": "D0RA10529E-(cit52)/*[position()=1]", "unstructured": "Available from: https://www.rcsb.org/ , (accessed November 11, 2020)" }, { "DOI": "10.1093/nar/gkg520", "author": "Schwede", "doi-asserted-by": "crossref", "first-page": "3381", "journal-title": "Nucleic Acids Res.", "key": "D0RA10529E-(cit53)/*[position()=1]", "volume": "31", "year": "2003" }, { "DOI": "10.1002/jcc.21256", "author": "Morris", "doi-asserted-by": "crossref", "first-page": "2785", "journal-title": "J. Comput. Chem.", "key": "D0RA10529E-(cit54)/*[position()=1]", "volume": "30", "year": "2009" }, { "author": "Case", "key": "D0RA10529E-(cit55)/*[position()=1]", "unstructured": "D. A.Case , R. M.Betz , D. S.Cerutti , T. E.Cheatham III , T. A.Darden , R. E.Duke , T. J.Giese , H.Gohlke , A. W.Goetz , N.Homeyer , S.Izadi , P.Janowski , J.Kaus , A.Kovalenko , T. S.Lee , S.LeGrand , P.Li , C.Lin , T.Luchko , R.Luo , B.Madej , D.Mermelstein , K. M.Merz , G.Monard , H.Nguyen , H. T.Nguyen , I.Omelyan , A.Onufriev , D. R.Roe , A.Roitberg , C.Sagui , C. L.Simmerling , W. M.Botello-Smith , J.Swails , R. C.Walker , J.Wang , R. M.Wolf , X.Wu , L.Xiao , and P. A.Kollman , AMBER 2016 , University of California , San Francisco , 2016 , https://ambermd.org/index", "volume-title": "AMBER 2016", "year": "2016" }, { "author": "Wang", "first-page": "U403", "journal-title": "J. Am. Chem. Soc.", "key": "D0RA10529E-(cit56)/*[position()=1]", "volume": "222", "year": "2001" }, { "key": "D0RA10529E-(cit57)/*[position()=1]", "unstructured": "Available from: https://molsoft.com/mprop/ , (accessed November 20, 2020)" }, { "DOI": "10.1093/bioinformatics/bty707", "author": "Yang", "doi-asserted-by": "crossref", "first-page": "1067", "journal-title": "Bioinformatics", "key": "D0RA10529E-(cit58)/*[position()=1]", "volume": "35", "year": "2019" }, { "DOI": "10.1186/1471-2334-14-S3-E24", "author": "Chikhale", "doi-asserted-by": "publisher", "journal-title": "BMC Infect. Dis.", "key": "D0RA10529E-(cit59)/*[position()=1]", "year": "2014" }, { "author": "Kerzare", "first-page": "1998", "issue": "11", "journal-title": "J. Braz. Chem. Soc.", "key": "D0RA10529E-(cit60)/*[position()=1]", "volume": "27", "year": "2016" }, { "key": "D0RA10529E-(cit61)/*[position()=1]", "unstructured": "Available from: https://www.sciencedaily.com/releases/2020/03/200317103815.htm , (accessed May 27, 2020)" }, { "DOI": "10.1101/cshperspect.a016303", "author": "Sokol", "doi-asserted-by": "crossref", "first-page": "a016303", "journal-title": "Cold Spring Harb. Perspect. Biol.", "key": "D0RA10529E-(cit62)/*[position()=1]", "volume": "7", "year": "2015" }, { "DOI": "10.1016/j.cell.2017.11.013", "author": "Kortlever", "doi-asserted-by": "crossref", "first-page": "1301", "journal-title": "Cell", "key": "D0RA10529E-(cit63)/*[position()=1]", "volume": "171", "year": "2017" }, { "author": "Chi", "key": "D0RA10529E-(cit64)/*[position()=1]", "unstructured": "H.Chi and R. A.Flavell , in MAP Kinase Signaling Protocols , Springer , 2010 , pp. 471–480", "volume-title": "MAP Kinase Signaling Protocols", "year": "2010" }, { "DOI": "10.2174/1871530320666200427112902", "author": "Magrone", "doi-asserted-by": "crossref", "first-page": "807", "journal-title": "Endocr. Metab. Immune Disord. - Drug Targets", "key": "D0RA10529E-(cit65)/*[position()=1]", "volume": "20", "year": "2020" } ], "reference-count": 65, "references-count": 65, "relation": {}, "resource": { "primary": { "URL": "https://xlink.rsc.org/?DOI=D0RA10529E" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "Combination of system biology to probe the anti-viral activity of andrographolide and its derivative against COVID-19", "type": "journal-article", "update-policy": "http://dx.doi.org/10.1039/rsc_crossmark_policy", "volume": "11" }

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