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

Source PDF All Studies Meta AnalysisMeta

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.

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

8 In Silico studies1-8

6 In Vitro studies9-14

2 In Vivo animal studies11,14

Important missing comments or errors? Let us know.

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

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

{ 'indexed': {'date-parts': [[2024, 5, 27]], 'date-time': '2024-05-27T11:14:50Z', 'timestamp': 1716808490527}, 'reference-count': 65, 'publisher': 'Royal Society of Chemistry (RSC)', 'issue': '9', 'license': [ { 'start': { 'date-parts': [[2021, 1, 27]], 'date-time': '2021-01-27T00:00:00Z', 'timestamp': 1611705600000}, 'content-version': 'vor', 'delay-in-days': 26, 'URL': 'http://creativecommons.org/licenses/by-nc/3.0/'}], 'content-domain': {'domain': ['rsc.org'], 'crossmark-restriction': True}, 'abstract': '<p>The present study aimed to investigate the binding affinity of andrographolide and its ' 'derivative<italic>i.e.</italic>14-deoxy-11,12-didehydroandrographolide with targets related ' 'to COVID-19 and their probable role in regulating multiple pathways in COVID-19 ' 'infection.</p>', 'DOI': '10.1039/d0ra10529e', 'type': 'journal-article', 'created': {'date-parts': [[2021, 1, 27]], 'date-time': '2021-01-27T09:55:12Z', 'timestamp': 1611741312000}, 'page': '5065-5079', 'update-policy': 'http://dx.doi.org/10.1039/rsc_crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 30, 'title': 'Combination of system biology to probe the anti-viral activity of andrographolide and its ' 'derivative against COVID-19', 'prefix': '10.1039', 'volume': '11', 'author': [ { 'ORCID': 'http://orcid.org/0000-0002-8187-2120', 'authenticated-orcid': False, 'given': 'Pukar', 'family': 'Khanal', 'sequence': 'first', 'affiliation': [ {'name': 'Department of Pharmacology and Toxicology'}, {'name': 'KLE College of Pharmacy Belagavi'}, {'name': 'KLE Academy of Higher Education and Research (KAHER)'}, {'name': 'Belagavi-590010'}, {'name': 'India'}]}, { 'given': 'Yadu Nandan', 'family': 'Dey', 'sequence': 'additional', 'affiliation': [ {'name': 'School of Pharmaceutical Technology'}, {'name': 'Adamas University'}, {'name': 'Kolkata-700126'}, {'name': 'India'}]}, { 'ORCID': 'http://orcid.org/0000-0003-2986-9546', 'authenticated-orcid': False, 'given': 'Rajesh', 'family': 'Patil', 'sequence': 'additional', 'affiliation': [ {'name': "Sinhgad Technical Education Society's"}, {'name': 'Smt. Kashibai Navale College of Pharmacy'}, {'name': 'Pune'}, {'name': 'India'}]}, { 'given': 'Rupesh', 'family': 'Chikhale', 'sequence': 'additional', 'affiliation': [ {'name': 'School of Pharmacy'}, {'name': 'University of East Anglia'}, {'name': 'Norwich'}, {'name': 'UK'}]}, { 'given': 'Manish M.', 'family': 'Wanjari', 'sequence': 'additional', 'affiliation': [ {'name': 'Regional Ayurveda Research Institute for Drug Development'}, {'name': 'Gwalior-474009'}, {'name': 'India'}]}, { 'ORCID': 'http://orcid.org/0000-0001-5564-2121', 'authenticated-orcid': False, 'given': 'Shailendra S.', 'family': 'Gurav', 'sequence': 'additional', 'affiliation': [ {'name': 'Department of Pharmacognosy'}, {'name': 'Goa College of Pharmacy'}, {'name': 'Goa University'}, {'name': 'Panjim'}, {'name': 'India'}]}, { 'given': 'B. M.', 'family': 'Patil', 'sequence': 'additional', 'affiliation': [ {'name': 'Department of Pharmacology and Toxicology'}, {'name': 'KLE College of Pharmacy Belagavi'}, {'name': 'KLE Academy of Higher Education and Research (KAHER)'}, {'name': 'Belagavi-590010'}, {'name': 'India'}]}, { 'given': 'Bhavana', 'family': 'Srivastava', 'sequence': 'additional', 'affiliation': [ {'name': 'Regional Ayurveda Research Institute for Drug Development'}, {'name': 'Gwalior-474009'}, {'name': 'India'}]}, { 'given': 'Sudesh N.', 'family': 'Gaidhani', 'sequence': 'additional', 'affiliation': [ {'name': 'Central Council for Research in Ayurvedic Sciences'}, {'name': 'New Delhi-110058'}, {'name': 'India'}]}], 'member': '292', 'published-online': {'date-parts': [[2021]]}, 'reference': [ { 'key': 'D0RA10529E-(cit1)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '727', 'DOI': '10.1056/NEJMoa2001017', 'volume': '382', 'author': 'Zhu', 'year': '2020', 'journal-title': 'N. Engl. J. Med.'}, { 'key': 'D0RA10529E-(cit2)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '536', 'DOI': '10.1038/s41564-020-0695-z', 'volume': '5', 'author': 'of the International', 'year': '2020', 'journal-title': 'Nat. Microbiol.'}, { 'key': 'D0RA10529E-(cit3)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '1', 'DOI': '10.1080/07391102.2020.1762741', 'author': 'Sinha', 'year': '2020', 'journal-title': 'J. Biomol. Struct. Dyn.'}, { 'key': 'D0RA10529E-(cit4)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '1294', 'DOI': '10.1164/rccm.200909-1427SO', 'volume': '181', 'author': 'Opitz', 'year': '2010', 'journal-title': 'Am. J. Respir. Crit. Care Med.'}, { 'key': 'D0RA10529E-(cit5)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '497', 'DOI': '10.1016/S0140-6736(20)30183-5', 'volume': '395', 'author': 'Huang', 'year': '2020', 'journal-title': 'Lancet'}, { 'key': 'D0RA10529E-(cit6)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '1061', 'DOI': '10.1001/jama.2020.1585', 'volume': '323', 'author': 'Wang', 'year': '2020', 'journal-title': 'Jama'}, { 'key': 'D0RA10529E-(cit7)/*[position()=1]', 'first-page': '1', 'author': 'Wan', 'year': '2020', 'journal-title': 'MedRxiv'}, { 'key': 'D0RA10529E-(cit8)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '420', 'DOI': '10.1016/S2213-2600(20)30076-X', 'volume': '8', 'author': 'Xu', 'year': '2020', 'journal-title': 'Lancet Respir. Med.'}, { 'key': 'D0RA10529E-(cit9)/*[position()=1]', 'first-page': '1157', 'volume': '21', 'author': 'Zhang', 'year': '2000', 'journal-title': 'Acta Pharmacol. Sin.'}, { 'key': 'D0RA10529E-(cit10)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '1', 'DOI': '10.1080/07391102.2020.1869588', 'author': 'Khanal', 'year': '2021', 'journal-title': 'J. Biomol. Struct. Dyn.'}, { 'key': 'D0RA10529E-(cit11)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '325', 'DOI': '10.1007/s13659-020-00260-2', 'volume': '10', 'author': 'Khanal', 'year': '2020', 'journal-title': 'Nat. Prod. Bioprospect.'}, { 'key': 'D0RA10529E-(cit12)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '41', 'DOI': '10.1016/S2225-4110(16)30055-4', 'volume': '1', 'author': 'Wen', 'year': '2011', 'journal-title': 'J. Tradit. Complement. Med.'}, { 'key': 'D0RA10529E-(cit13)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '108', 'DOI': '10.1016/j.jep.2008.07.048', 'volume': '120', 'author': 'Chen', 'year': '2008', 'journal-title': 'J. Ethnopharmacol.'}, { 'key': 'D0RA10529E-(cit14)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '2018', 'DOI': '10.1248/bpb.31.2018', 'volume': '31', 'author': 'Lin', 'year': '2008', 'journal-title': 'Biol. Pharm. Bull.'}, { 'key': 'D0RA10529E-(cit15)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '7940', 'DOI': '10.1016/j.bmc.2010.09.035', 'volume': '18', 'author': 'Ryu', 'year': '2010', 'journal-title': 'Bioorg. Med. Chem.'}, { 'key': 'D0RA10529E-(cit16)/*[position()=1]', 'first-page': '1', 'author': 'Chikhale', 'year': '2020', 'journal-title': 'J. Biomol. Struct. Dyn.'}, { 'key': 'D0RA10529E-(cit17)/*[position()=1]', 'first-page': '1', 'author': 'Chikhale', 'year': '2020', 'journal-title': 'J. Biomol. Struct. Dyn.'}, { 'key': 'D0RA10529E-(cit18)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '1', 'DOI': '10.1080/07391102.2020.1762741', 'author': 'Sinha', 'year': '2020', 'journal-title': 'J. Biomol. Struct. Dyn.'}, { 'key': 'D0RA10529E-(cit19)/*[position()=1]', 'doi-asserted-by': 'publisher', 'author': 'Chikhale', 'year': '2021', 'journal-title': 'Mol. Divers.', 'DOI': '10.1007/s11030-021-10183-w'}, { 'key': 'D0RA10529E-(cit20)/*[position()=1]', 'first-page': '100504', 'author': 'Patil', 'year': '2020', 'journal-title': 'Inform. Med. Unlocked'}, { 'key': 'D0RA10529E-(cit21)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '2405', 'DOI': '10.2174/1381612054367481', 'volume': '11', 'author': 'Mahady', 'year': '2005', 'journal-title': 'Curr. Pharm. Des.'}, { 'key': 'D0RA10529E-(cit22)/*[position()=1]', 'first-page': '210', 'volume': '10', 'author': 'Sofowora', 'year': '2013', 'journal-title': 'Afr. J. Tradit. Complement. Altern. Med.'}, { 'key': 'D0RA10529E-(cit23)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '858', 'DOI': '10.1016/j.apjtb.2015.06.004', 'volume': '5', 'author': 'Bahmani', 'year': '2015', 'journal-title': 'Asian Pac. J. Trop. Biomed.'}, { 'key': 'D0RA10529E-(cit24)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '14179', 'DOI': '10.1038/srep14179', 'volume': '5', 'author': 'Wintachai', 'year': '2015', 'journal-title': 'Sci. Rep.'}, { 'key': 'D0RA10529E-(cit25)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '67', 'DOI': '10.4308/hjb.22.2.67', 'volume': '22', 'author': 'Pongtuluran', 'year': '2015', 'journal-title': 'HAYATI J. Biosci.'}, { 'key': 'D0RA10529E-(cit26)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '76', 'DOI': '10.1186/s12906-015-0598-3', 'volume': '15', 'author': 'Mopuri', 'year': '2015', 'journal-title': 'BMC Complementary Altern. Med.'}, { 'key': 'D0RA10529E-(cit27)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '995', 'DOI': '10.1021/np50097a002', 'volume': '56', 'author': 'Puri', 'year': '1993', 'journal-title': 'J. Nat. Prod.'}, { 'key': 'D0RA10529E-(cit28)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '579518', 'DOI': '10.1155/2011/579518', 'volume': '2011', 'author': 'Mishra', 'year': '2011', 'journal-title': 'J. Trop. Med.'}, { 'key': 'D0RA10529E-(cit29)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '191', 'DOI': '10.1038/aps.2009.205', 'volume': '31', 'author': 'Wang', 'year': '2010', 'journal-title': 'Acta Pharmacol. Sin.'}, { 'key': 'D0RA10529E-(cit30)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '611', 'DOI': '10.1007/s00705-016-3166-3', 'volume': '162', 'author': 'Gupta', 'year': '2017', 'journal-title': 'Arch. Virol.'}, { 'key': 'D0RA10529E-(cit31)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '167', 'DOI': '10.1016/j.actatropica.2016.07.009', 'volume': '163', 'author': 'Edwin', 'year': '2016', 'journal-title': 'Acta Trop.'}, { 'key': 'D0RA10529E-(cit32)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': 'S624', 'DOI': '10.1016/S2222-1808(14)60692-7', 'volume': '4', 'author': 'Seniya', 'year': '2014', 'journal-title': 'Asian Pac. J. Trop. Dis.'}, { 'key': 'D0RA10529E-(cit33)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '237', 'DOI': '10.1111/bph.12440', 'volume': '171', 'author': 'Lee', 'year': '2014', 'journal-title': 'Br. J. Pharmacol.'}, { 'key': 'D0RA10529E-(cit34)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '1385', 'DOI': '10.1248/bpb.32.1385', 'volume': '32', 'author': 'Chen', 'year': '2009', 'journal-title': 'Biol. Pharm. Bull.'}, { 'key': 'D0RA10529E-(cit35)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '36', 'DOI': '10.1016/j.antiviral.2005.07.002', 'volume': '68', 'author': 'Lin', 'year': '2005', 'journal-title': 'Antiviral Res.'}, { 'key': 'D0RA10529E-(cit36)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '1069', 'DOI': '10.1002/ptr.1765', 'volume': '19', 'author': 'Wiart', 'year': '2005', 'journal-title': 'Phytother Res.'}, { 'key': 'D0RA10529E-(cit37)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '95', 'DOI': '10.1016/j.antiviral.2016.07.020', 'volume': '133', 'author': 'Cai', 'year': '2016', 'journal-title': 'Antiviral Res.'}, { 'key': 'D0RA10529E-(cit38)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '82', 'DOI': '10.1016/j.antiviral.2015.03.008', 'volume': '118', 'author': 'Cai', 'year': '2015', 'journal-title': 'Antiviral Res.'}, { 'key': 'D0RA10529E-(cit39)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '104885', 'DOI': '10.1016/j.antiviral.2020.104885', 'volume': '181', 'author': 'Cai', 'year': '2020', 'journal-title': 'Antiviral Res.'}, { 'key': 'D0RA10529E-(cit40)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '1', 'DOI': '10.1080/07391102.2020.1760136', 'author': 'Enmozhi', 'year': '2020', 'journal-title': 'J. Biomol. Struct. Dyn.'}, { 'key': 'D0RA10529E-(cit41)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '907', 'DOI': '10.1002/cmdc.202000223', 'volume': '15', 'author': 'Ghosh', 'year': '2020', 'journal-title': 'ChemMedChem'}, { 'issue': '12', 'key': 'D0RA10529E-(cit42)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '5771', 'DOI': '10.1021/acs.jcim.0c00491', 'volume': '60', 'author': 'Ngo', 'year': '2020', 'journal-title': 'J. Chem. Inf. Model.'}, { 'key': 'D0RA10529E-(cit43)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '3922', 'DOI': '10.3390/ijms21113922', 'volume': '21', 'author': 'Hagar', 'year': '2020', 'journal-title': 'Int. J. Mol. Sci.'}, { 'key': 'D0RA10529E-(cit44)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '3193', 'DOI': '10.3390/molecules25143193', 'volume': '25', 'author': 'Olubiyi', 'year': '2020', 'journal-title': 'Molecules'}, { 'key': 'D0RA10529E-(cit45)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '1815', 'DOI': '10.4155/fmc-2020-0165', 'volume': '12', 'author': 'Ferraz', 'year': '2020', 'journal-title': 'Future Med. Chem.'}, { 'key': 'D0RA10529E-(cit46)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '225', 'DOI': '10.3390/md18040225', 'volume': '18', 'author': 'Gentile', 'year': '2020', 'journal-title': 'Mar. Drugs'}, { 'key': 'D0RA10529E-(cit47)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '409', 'DOI': '10.1126/science.abb3405', 'volume': '368', 'author': 'Zhang', 'year': '2020', 'journal-title': 'Science'}, { 'key': 'D0RA10529E-(cit48)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '152336', 'DOI': '10.1016/j.tetlet.2020.152336', 'volume': '61', 'author': 'Shahinshavali', 'year': '2020', 'journal-title': 'Tetrahedron Lett.'}, { 'key': 'D0RA10529E-(cit49)/*[position()=1]', 'unstructured': 'Available from: https://pubchem.ncbi.nlm.nih.gov/ , (accessed November ' '17, 2020)'}, { 'key': 'D0RA10529E-(cit50)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '2062', 'DOI': '10.1093/bioinformatics/btt322', 'volume': '29', 'author': 'Lagunin', 'year': '2013', 'journal-title': 'Bioinformatics'}, { 'key': 'D0RA10529E-(cit51)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': 'D362', 'DOI': '10.1093/nar/gkw937', 'volume': '45', 'author': 'Szklarczyk', 'year': '2017', 'journal-title': 'Nucleic Acids Res.'}, { 'key': 'D0RA10529E-(cit52)/*[position()=1]', 'unstructured': 'Available from: https://www.rcsb.org/ , (accessed November 11, 2020)'}, { 'key': 'D0RA10529E-(cit53)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '3381', 'DOI': '10.1093/nar/gkg520', 'volume': '31', 'author': 'Schwede', 'year': '2003', 'journal-title': 'Nucleic Acids Res.'}, { 'key': 'D0RA10529E-(cit54)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '2785', 'DOI': '10.1002/jcc.21256', 'volume': '30', 'author': 'Morris', 'year': '2009', 'journal-title': 'J. Comput. Chem.'}, { 'key': 'D0RA10529E-(cit55)/*[position()=1]', 'volume-title': 'AMBER 2016', 'author': 'Case', 'year': '2016', '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'}, { 'key': 'D0RA10529E-(cit56)/*[position()=1]', 'first-page': 'U403', 'volume': '222', 'author': 'Wang', 'year': '2001', 'journal-title': 'J. Am. Chem. Soc.'}, { 'key': 'D0RA10529E-(cit57)/*[position()=1]', 'unstructured': 'Available from: https://molsoft.com/mprop/ , (accessed November 20, ' '2020)'}, { 'key': 'D0RA10529E-(cit58)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '1067', 'DOI': '10.1093/bioinformatics/bty707', 'volume': '35', 'author': 'Yang', 'year': '2019', 'journal-title': 'Bioinformatics'}, { 'key': 'D0RA10529E-(cit59)/*[position()=1]', 'doi-asserted-by': 'publisher', 'author': 'Chikhale', 'year': '2014', 'journal-title': 'BMC Infect. Dis.', 'DOI': '10.1186/1471-2334-14-S3-E24'}, { 'issue': '11', 'key': 'D0RA10529E-(cit60)/*[position()=1]', 'first-page': '1998', 'volume': '27', 'author': 'Kerzare', 'year': '2016', 'journal-title': 'J. Braz. Chem. Soc.'}, { 'key': 'D0RA10529E-(cit61)/*[position()=1]', 'unstructured': 'Available from: ' 'https://www.sciencedaily.com/releases/2020/03/200317103815.htm , ' '(accessed May 27, 2020)'}, { 'key': 'D0RA10529E-(cit62)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': 'a016303', 'DOI': '10.1101/cshperspect.a016303', 'volume': '7', 'author': 'Sokol', 'year': '2015', 'journal-title': 'Cold Spring Harb. Perspect. Biol.'}, { 'key': 'D0RA10529E-(cit63)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '1301', 'DOI': '10.1016/j.cell.2017.11.013', 'volume': '171', 'author': 'Kortlever', 'year': '2017', 'journal-title': 'Cell'}, { 'key': 'D0RA10529E-(cit64)/*[position()=1]', 'volume-title': 'MAP Kinase Signaling Protocols', 'author': 'Chi', 'year': '2010', 'unstructured': 'H.Chi and R. A.Flavell , in MAP Kinase Signaling Protocols , Springer , ' '2010 , pp. 471–480'}, { 'key': 'D0RA10529E-(cit65)/*[position()=1]', 'doi-asserted-by': 'crossref', 'first-page': '807', 'DOI': '10.2174/1871530320666200427112902', 'volume': '20', 'author': 'Magrone', 'year': '2020', 'journal-title': 'Endocr. Metab. Immune Disord. - Drug Targets'}], 'container-title': 'RSC Advances', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'http://pubs.rsc.org/en/content/articlepdf/2021/RA/D0RA10529E', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2024, 4, 17]], 'date-time': '2024-04-17T18:28:59Z', 'timestamp': 1713378539000}, 'score': 1, 'resource': {'primary': {'URL': 'https://xlink.rsc.org/?DOI=D0RA10529E'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2021]]}, 'references-count': 65, 'journal-issue': {'issue': '9', 'published-print': {'date-parts': [[2021, 1, 27]]}}, 'URL': 'http://dx.doi.org/10.1039/D0RA10529E', 'relation': {}, 'ISSN': ['2046-2069'], 'subject': [], 'container-title-short': 'RSC Adv.', 'published': {'date-parts': [[2021]]}, 'assertion': [ { 'value': 'This document is Similarity Check deposited', 'name': 'similarity_check', 'explanation': {'URL': 'https://www.crossref.org/services/similarity-check/'}, 'group': {'name': 'similarity_check', 'label': 'SIMILARITY CHECK'}}, { 'value': 'Pukar Khanal (ORCID)', 'URL': 'http://orcid.org/0000-0002-8187-2120', 'name': 'identifier', 'group': {'name': 'author_identifiers', 'label': 'IDENTIFIERS'}}, { 'value': 'Rajesh Patil (ORCID)', 'URL': 'http://orcid.org/0000-0003-2986-9546', 'name': 'identifier', 'group': {'name': 'author_identifiers', 'label': 'IDENTIFIERS'}}, { 'value': 'Shailendra S. Gurav (ORCID)', 'URL': 'http://orcid.org/0000-0001-5564-2121', 'name': 'identifier', 'group': {'name': 'author_identifiers', 'label': 'IDENTIFIERS'}}, { 'value': 'Shailendra S. Gurav (ResearcherID)', 'URL': 'http://www.researcherid.com/rid/AAO-4240-2020', 'name': 'identifier', 'group': {'name': 'author_identifiers', 'label': 'IDENTIFIERS'}}, { 'value': 'Single-blind', 'order': 2, 'name': 'peer_review_method', 'group': {'name': 'peer_review_method', 'label': 'PEER REVIEW METHOD'}}, { 'value': 'Received 15 December 2020; Accepted 11 January 2021; Version of Record ' 'published 27 January 2021', 'order': 1, 'name': 'history', 'group': {'name': 'publication_history', 'label': 'PUBLICATION HISTORY'}}]}

Download Image

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.

Submit

Post

@CovidAnalysis

FAQ

Public domain CC0 1.0