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2000
Volume 21, Issue 2
  • ISSN: 1573-4099
  • E-ISSN: 1875-6697

Abstract

Introduction

Arthritis is the cause of morbidity associated with Chikungunya virus (CHIKV) infection. It persists even after the virus has been cleared from the body. MBZM-N-IBT was earlier shown to inhibit (CHIKV) infection and .

Objectives

The objective of this study is to determine the ability of MBZM-N-IBT to manage arthritis independent of CHIKV infection.

Methods

The acute toxicity of MBZM-N-IBT was determined to find a permissible oral dose. Effects against inflammation and arthritis were determined in relevant preclinical models. Network pharmacology was used to propose possible modes of action.

Results

It showed no acute toxicity orally, with an estimated LD of more than 5000 mg/kg in rats. It significantly reduced inflammation. Its effect against Complete Freund's Adjuvant (CFA) induced arthritis was comparable to that of Diclofenac sodium. Network pharmacology analysis revealed that MBZM-N-IBT can potentially interfere with multiple targets and pathways. MMP12 and CTSD were found to be the most probable hub targets of MBZM-N-IBT for its effect against arthritis.

Conclusion

In conclusion, MBZM-N-IBT is safe at 50 mg/kg and can manage arthritis independent of CHIKV infection through modulation of multiple pathways and arthritis-associated targets.

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References

  1. RougeronV. SamI.C. CaronM. NkogheD. LeroyE. RoquesP. Chikungunya, a paradigm of neglected tropical disease that emerged to be a new health global risk.J. Clin. Virol.20156414415210.1016/j.jcv.2014.08.03225453326
    [Google Scholar]
  2. MoizéisR.N.C. FernandesT.A.A.M. GuedesP.M.M. PereiraH.W.B. LanzaD.C.F. AzevedoJ.W.V. GalvãoJ.M.A. FernandesJ.V. Chikungunya fever: a threat to global public health.Pathog. Glob. Health2018112418219410.1080/20477724.2018.147877729806537
    [Google Scholar]
  3. PathakH. MohanM.C. RavindranV. Chikungunya Arthritis.Clin. Med.201919381385
    [Google Scholar]
  4. MahishC. DeS. ChatterjeeS. GhoshS. KeshryS.S. MukherjeeT. KhamaruS. TungK.S. SubudhiB.B. ChattopadhyayS. ChattopadhyayS. TLR4 is one of the receptors for Chikungunya virus envelope protein E2 and regulates virus induced pro-inflammatory responses in host macrophages.Front. Immunol.202314113980810.3389/fimmu.2023.113980837153546
    [Google Scholar]
  5. DeS. MamidiP. GhoshS. KeshryS.S. MahishC. PaniS.S. LahaE. RayA. DateyA. ChatterjeeS. SinghS. MukherjeeT. KhamaruS. ChattopadhyayS. SubudhiB.B. ChattopadhyayS. Telmisartan Restricts Chikungunya Virus Infection In Vitro and In Vivo through the AT1/PPAR-γ/MAPKs Pathways.Antimicrob. Agents Chemother.2022661e01489-2110.1128/AAC.01489‑2134748384
    [Google Scholar]
  6. SubudhiB.B. ChattopadhyayS. MishraP. KumarA. Current Strategies for Inhibition of Chikungunya Infection.Viruses201810523510.3390/v1005023529751486
    [Google Scholar]
  7. SundyJ.S. COX-2 inhibitors in rheumatoid arthritis.Curr. Rheumatol. Rep.200131869110.1007/s11926‑001‑0055‑911177775
    [Google Scholar]
  8. HochbergM. COX-2 selective inhibitors in the treatment of arthritis: a rheumatologist perspective.Curr. Top. Med. Chem.20055544344810.2174/156802605420169515974939
    [Google Scholar]
  9. HunterL. WoodD. DarganP.I. The patterns of toxicity and management of acute nonsteroidal anti-inflammatory drug (NSAID) overdose.Open Access Emerg. Med.20113394810.2147/OAEM.S2279527147851
    [Google Scholar]
  10. ParoliniM. Toxicity of the Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) acetylsalicylic acid, paracetamol, diclofenac, ibuprofen and naproxen towards freshwater invertebrates: A review.Sci. Total Environ.202074014004310.1016/j.scitotenv.2020.14004332559537
    [Google Scholar]
  11. SolomonD.H. HusniM.E. LibbyP.A. YeomansN.D. LincoffA.M. LϋscherT.F. MenonV. BrennanD.M. WisniewskiL.M. NissenS.E. BorerJ.S. The Risk of Major NSAID Toxicity with Celecoxib, Ibuprofen, or Naproxen: A Secondary Analysis of the PRECISION Trial.Am. J. Med.20171301214151422.e410.1016/j.amjmed.2017.06.02828756267
    [Google Scholar]
  12. SaadJ. PellegriniM.V. Nonsteroidal Anti-Inflammatory Drugs (NSAID).Toxicity2018
    [Google Scholar]
  13. BessoneF. Non-steroidal anti-inflammatory drugs: What is the actual risk of liver damage?World J. Gastroenterol.201016455651566110.3748/wjg.v16.i45.565121128314
    [Google Scholar]
  14. MeunierL. LarreyD. Recent Advances in Hepatotoxicity of Non Steroidal Anti-inflammatory Drugs.Ann. Hepatol.201817218719110.5604/01.3001.0010.863329469052
    [Google Scholar]
  15. ClavéS. Rousset-RouvièreC. DanielL. TsimaratosM. The Invisible Threat of Non-steroidal Anti-inflammatory Drugs for Kidneys.Front Pediatr.2019752010.3389/fped.2019.0052031921731
    [Google Scholar]
  16. LucasG.N.C. LeitãoA.C.C. AlencarR.L. XavierR.M.F. DaherE.D.F. Silva JuniorG.B. Pathophysiological aspects of nephropathy caused by non-steroidal anti-inflammatory drugs.J. Bras. Nefrol.201941112413010.1590/2175‑8239‑jbn‑2018‑010730281062
    [Google Scholar]
  17. YiT. ZhaoZ.Z. YuZ.L. ChenH.B. Comparison of the anti-inflammatory and anti-nociceptive effects of three medicinal plants known as “Snow Lotus” herb in traditional Uighur and Tibetan medicines.J. Ethnopharmacol.2010128240541110.1016/j.jep.2010.01.03720083181
    [Google Scholar]
  18. FanJ.Y. ChenH.B. ZhuL. ChenH.L. ZhaoZ.Z. YiT. Saussurea medusa, source of the medicinal herb snow lotus: a review of its botany, phytochemistry, pharmacology and toxicology.Phytochem. Rev.201514335336610.1007/s11101‑015‑9408‑2
    [Google Scholar]
  19. ChenQ. ZhuL. YipK.M. TangY. LiuY. JiangT. ZhangJ. ZhaoZ. YiT. ChenH. A hybrid platform featuring nanomagnetic ligand fishing for discovering COX-2 selective inhibitors from aerial part of Saussurea laniceps Hand.-Mazz.J. Ethnopharmacol.202127111384910.1016/j.jep.2021.11384933485983
    [Google Scholar]
  20. ChikW.I. ZhuL. FanL.L. YiT. ZhuG.Y. GouX.J. TangY.N. XuJ. YeungW.P. ZhaoZ.Z. YuZ.L. ChenH.B. Saussurea involucrata: A review of the botany, phytochemistry and ethnopharmacology of a rare traditional herbal medicine.J. Ethnopharmacol.2015172446010.1016/j.jep.2015.06.03326113182
    [Google Scholar]
  21. MishraP. KumarA. MamidiP. KumarS. BasantrayI. SaswatT. DasI. NayakT.K. ChattopadhyayS. SubudhiB.B. ChattopadhyayS. Inhibition of Chikungunya Virus Replication by 1-[(2-Methylbenzimidazol-1-yl) Methyl]-2-Oxo-Indolin-3-ylidene] Amino] Thiourea(MBZM-N-IBT).Sci. Rep.2016612012210.1038/srep2012226843462
    [Google Scholar]
  22. KumarA. DeS. MoharanaA.K. NayakT.K. SaswatT. DateyA. MamidiP. MishraP. SubudhiB.B. ChattopadhyayS. Inhibition of Herpes Simplex Virus-1 Infection by MBZM-N-IBT: In Silico and in Vitro Studies.Virol. J.202118
    [Google Scholar]
  23. DeS. GhoshS. KeshryS.S. MahishC. MohapatraC. GuruA. MamidiP. DateyA. PaniS.S. VasudevanD. BeuriaT.K. ChattopadhyayS. SubudhiB.B. ChattopadhyayS. MBZM-N-IBT, a Novel Small Molecule, Restricts Chikungunya Virus Infection by Targeting nsP2 Protease Activity In Vitro, In Vivo, and Ex Vivo.Antimicrob. Agents Chemother.2022667e00463-2210.1128/aac.00463‑2235766508
    [Google Scholar]
  24. HawmanD.W. StoermerK.A. MontgomeryS.A. PalP. OkoL. DiamondM.S. MorrisonT.E. Chronic joint disease caused by persistent Chikungunya virus infection is controlled by the adaptive immune response.J. Virol.20138724138781388810.1128/JVI.02666‑1324131709
    [Google Scholar]
  25. MuhammadJ. KhanA. AliA. FangL. YanjingW. XuQ. WeiD.Q. Network Pharmacology: Exploring the Resources and Methodologies.Curr. Top. Med. Chem.2018181294996410.2174/156802661866618033014135129600765
    [Google Scholar]
  26. MajhiP.K. SayyadS. GaurM. KedarG. RathodS. SahuR. PradhanP.K. TripathyS. GhoshG. SubudhiB.B. Tinospora cordifolia Extract Enhances Dextromethorphan Bioavailability: Implications for Alzheimer’s Disease.ACS Omega2024922236342364810.1021/acsomega.4c0121938854540
    [Google Scholar]
  27. JonssonM. JestoiM. NathanailA.V. KokkonenU.M. AnttilaM. KoivistoP. KarhunenP. PeltonenK. Application of OECD Guideline 423 in assessing the acute oral toxicity of moniliformin.Food Chem. Toxicol.201353273210.1016/j.fct.2012.11.02323201451
    [Google Scholar]
  28. MohapatraT.K. NayakR.R. SubudhiB.B. Exploration of anti-inflammatory and hepatoprotective effect of curcumin on co-administration with acetylsalicylic acid.J. Pharm. Pharmacogn. Res.20197131032210.56499/jppres19.601_7.5.310
    [Google Scholar]
  29. GomesR.P. BressanE. SilvaT.M. GevaerdM.S. TonussiC.R. DomenechS.C. Padronização de modelo experimental adequado a estudos do efeito do exercício na artrite.Einstein (Sao Paulo)2013111768210.1590/S1679‑4508201300010001423579748
    [Google Scholar]
  30. MahdiH.J. KhanN.A.K. AsmawiM.Z. Bin MahmudR. A/L MurugaiyahV. In Vivo Anti-Arthritic and Anti-Nociceptive Effects of Ethanol Extract of Moringa Oleifera Leaves on Complete Freund’s Adjuvant (CFA)-Induced Arthritis in Rats.Integr. Med. Res.20187859410.1016/j.imr.2017.11.00229629295
    [Google Scholar]
  31. WangZ.Z. LiuF. GongY.F. HuangT.Y. ZhangX.M. HuangX.Y. Antiarthritic Effects of Sorafenib in Rats with Adjuvant‐Induced Arthritis.Anat. Rec. (Hoboken)201830191519152610.1002/ar.2385629752865
    [Google Scholar]
  32. MehtaA. SethiyaN.K. MehtaC. ShahG.B. Anti–arthritis activity of roots of Hemidesmus indicus R.Br. (Anantmul) in rats.Asian Pac. J. Trop. Med.20125213013510.1016/S1995‑7645(12)60011‑X22221757
    [Google Scholar]
  33. LiuJ.Y. HouY.L. CaoR. QiuH.X. ChengG.H. TuR. WangL. ZhangJ.L. LiuD. Protodioscin ameliorates oxidative stress, inflammation and histology outcome in Complete Freund’s adjuvant induced arthritis rats.Apoptosis201722111454146010.1007/s10495‑017‑1420‑028916869
    [Google Scholar]
  34. AndersonG.D. HauserS.D. McGarityK.L. BremerM.E. IsaksonP.C. GregoryS.A. Selective inhibition of cyclooxygenase (COX)-2 reverses inflammation and expression of COX-2 and interleukin 6 in rat adjuvant arthritis.J. Clin. Invest.199697112672267910.1172/JCI1187178647962
    [Google Scholar]
  35. WangX. ShenY. WangS. LiS. ZhangW. LiuX. LaiL. PeiJ. LiH. PharmMapper 2017 update: a web server for potential drug target identification with a comprehensive target pharmacophore database.Nucleic Acids Res.201745W1W356W36010.1093/nar/gkx37428472422
    [Google Scholar]
  36. PiñeroJ. Ramírez-AnguitaJ.M. Saüch-PitarchJ. RonzanoF. CentenoE. SanzF. FurlongL.I. The DisGeNET Knowledge Platform for Disease Genomics: 2019 Update.Nucleic Acids Res.201931680165
    [Google Scholar]
  37. PiñeroJ. BravoÀ. Queralt-RosinachN. Gutiérrez-SacristánA. Deu-PonsJ. CentenoE. García-GarcíaJ. SanzF. FurlongL.I. DisGeNET: a comprehensive platform integrating information on human disease-associated genes and variants.Nucleic Acids Res.201745D1D833D83910.1093/nar/gkw94327924018
    [Google Scholar]
  38. ChenE.Y. TanC.M. KouY. DuanQ. WangZ. MeirellesG.V. ClarkN.R. Ma’ayanA. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool.BMC Bioinformatics201314112810.1186/1471‑2105‑14‑12823586463
    [Google Scholar]
  39. KuleshovM.V. JonesM.R. RouillardA.D. FernandezN.F. DuanQ. WangZ. KoplevS. JenkinsS.L. JagodnikK.M. LachmannA. McDermottM.G. MonteiroC.D. GundersenG.W. Ma’ayanA. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update.Nucleic Acids Res.201644W1W90W9710.1093/nar/gkw37727141961
    [Google Scholar]
  40. XieZ. BaileyA. KuleshovM.V. ClarkeD.J.B. EvangelistaJ.E. JenkinsS.L. LachmannA. WojciechowiczM.L. KropiwnickiE. JagodnikK.M. JeonM. Ma’ayanA. Gene Set Knowledge Discovery with Enrichr.Curr. Protoc.202113e9010.1002/cpz1.9033780170
    [Google Scholar]
  41. ShannonP. MarkielA. OzierO. BaligaN.S. WangJ.T. RamageD. AminN. SchwikowskiB. IdekerT. Cytoscape: a software environment for integrated models of biomolecular interaction networks.Genome Res.200313112498250410.1101/gr.123930314597658
    [Google Scholar]
  42. AssenovY. RamírezF. SchelhornS.E. LengauerT. AlbrechtM. Computing topological parameters of biological networks.Bioinformatics200824228228410.1093/bioinformatics/btm55418006545
    [Google Scholar]
  43. FriesnerR.A. MurphyR.B. RepaskyM.P. FryeL.L. GreenwoodJ.R. HalgrenT.A. SanschagrinP.C. MainzD.T. Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes.J. Med. Chem.200649216177619610.1021/jm051256o17034125
    [Google Scholar]
  44. FriesnerR.A. BanksJ.L. MurphyR.B. HalgrenT.A. KlicicJ.J. MainzD.T. RepaskyM.P. KnollE.H. ShelleyM. PerryJ.K. ShawD.E. FrancisP. ShenkinP.S. Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy.J. Med. Chem.20044771739174910.1021/jm030643015027865
    [Google Scholar]
  45. HalgrenT.A. MurphyR.B. FriesnerR.A. BeardH.S. FryeL.L. PollardW.T. BanksJ.L. Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening.J. Med. Chem.20044771750175910.1021/jm030644s15027866
    [Google Scholar]
  46. Madhavi SastryG. AdzhigireyM. DayT. AnnabhimojuR. ShermanW. Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments.J. Comput. Aided Mol. Des.201327322123410.1007/s10822‑013‑9644‑823579614
    [Google Scholar]
  47. MoharanaA.K. DashR.N. MahanandiaN.C. SubudhiB.B. Synthesis and Anti-Inflammatory Activity Evaluation of Some Benzimidazole Derivatives.Pharm. Chem. J.20225681070107410.1007/s11094‑022‑02755‑336405379
    [Google Scholar]
  48. DashR.N. PrabhuduttaM. DeS. SwainR.P. MoharanaA.K. SubudhiB.B. ChattopadhyayS. Conjugates of ibuprofen inhibit CHIKV infection and inflammation.Mol. Divers.202310.1007/s11030‑023‑10654‑237085737
    [Google Scholar]
  49. MohapatraT.K. MoharanaA.K. SwainR.P. SubudhiB.B. Coamorphisation of acetyl salicylic acid and curcumin for enhancing dissolution, anti-inflammatory effect and minimizing gastro toxicity.J. Drug Deliv. Sci. Technol.20216110211910.1016/j.jddst.2020.102119
    [Google Scholar]
  50. DashR.N. RayA. MamidiP. DeS. MohapatraT.K. MoharanaA.K. MukherjeeT. GhoshS. ChattopadhyayS. SubudhiB.B. ChattopadhyayS. Salicylic Acid Conjugate of Telmisartan Inhibits Chikungunya Virus Infection and Inflammation.ACS Omega20249114615610.1021/acsomega.3c0076338222605
    [Google Scholar]
  51. HolderbachS. AdamL. JayaramB. WadeR.C. MukherjeeG. RASPD+: Fast Protein-Ligand Binding Free Energy Prediction Using Simplified Physicochemical Features.Front. Mol. Biosci.2020760106510.3389/fmolb.2020.60106533392260
    [Google Scholar]
  52. SoniA. BhatR. JayaramB. Improving the binding affinity estimations of protein–ligand complexes using machine-learning facilitated force field method.J. Comput. Aided Mol. Des.202034881783010.1007/s10822‑020‑00305‑132185583
    [Google Scholar]
  53. LiuM. SunH. WangX. KoikeT. MishimaH. IkedaK. WatanabeT. OchiaiN. FanJ. Association of increased expression of macrophage elastase (matrix metalloproteinase 12) with rheumatoid arthritis.Arthritis Rheum.200450103112311710.1002/art.2056715476203
    [Google Scholar]
  54. ItohT. MatsudaH. TaniokaM. KuwabaraK. ItoharaS. SuzukiR. The role of matrix metalloproteinase-2 and matrix metalloproteinase-9 in antibody-induced arthritis.J. Immunol.200216952643264710.4049/jimmunol.169.5.264312193736
    [Google Scholar]
  55. BehlT. ChadhaS. SehgalA. SinghS. SharmaN. KaurR. BhatiaS. Al-HarrasiA. ChigurupatiS. AlhowailA. BungauS. Exploring the role of cathepsin in rheumatoid arthritis.Saudi J. Biol. Sci.202229140241010.1016/j.sjbs.2021.09.01435002435
    [Google Scholar]
  56. HardyR.S. FilerA. CooperM.S. ParsonageG. RazaK. HardieD.L. RabbittE.H. StewartP.M. BuckleyC.D. HewisonM. Differential expression, function and response to inflammatory stimuli of 11β-hydroxysteroid dehydrogenase type 1 in human fibroblasts: a mechanism for tissue-specific regulation of inflammation.Arthritis Res. Ther.200684R10810.1186/ar199316846535
    [Google Scholar]
  57. RodenhuisS. KremerJ.M. BertinoJ.R. Increase of dihydrofolate reductase in peripheral blood lymphocytes of rheumatoid arthritis patients treated with low‐dose oral methotrexate.Arthritis Rheum.198730436937410.1002/art.17803004023580007
    [Google Scholar]
  58. BartonA. ThomsonW. KeX. EyreS. HinksA. BowesJ. PlantD. GibbonsL.J. WilsonA.G. BaxD.E. MorganA.W. EmeryP. SteerS. HockingL. ReidD.M. WordsworthP. HarrisonP. WorthingtonJ. Rheumatoid arthritis susceptibility loci at chromosomes 10p15, 12q13 and 22q13.Nat. Genet.200840101156115910.1038/ng.21818794857
    [Google Scholar]
  59. BazsóA. KövesdiA. RásonyiR. NagyE. PoórG. PatócsA. KissE. Glucocorticoid receptor polymorphisms in rheumatoid arthritis: results from a single centre.Clin. Exp. Rheumatol.202038585886331820730
    [Google Scholar]
  60. NarH. WerleK. BauerM.M.T. DollingerH. JungB. 2001
  61. GrädlerU. CzodrowskiP. TsaklakidisC. KleinM. WerkmannD. LindemannS. MaskosK. LeuthnerB. Structure-based optimization of non-peptidic Cathepsin D inhibitors.Bioorg. Med. Chem. Lett.201424174141415010.1016/j.bmcl.2014.07.05425086681
    [Google Scholar]
  62. ShulgaD.A. IvanovN.N. PalyulinV.A. In Silico Structure-Based Approach for Group Efficiency Estimation in Fragment-Based Drug Design Using Evaluation of Fragment Contributions.Molecules2022276198510.3390/molecules2706198535335347
    [Google Scholar]
  63. KennyP.W. The nature of ligand efficiency.J. Cheminform.2019111810.1186/s13321‑019‑0330‑230706294
    [Google Scholar]
  64. MurrayC.W. ErlansonD.A. HopkinsA.L. KeserüG.M. LeesonP.D. ReesD.C. ReynoldsC.H. RichmondN.J. Validity of ligand efficiency metrics.ACS Med. Chem. Lett.20145661661810.1021/ml500146d24944729
    [Google Scholar]
  65. WardJ.R. Update on ibuprofen for rheumatoid arthritis.Am. J. Med.19847713910.1016/S0002‑9343(84)80012‑16380279
    [Google Scholar]
  66. NielenM.M.J. van SchaardenburgD. ReesinkH.W. TwiskJ.W. van de StadtR.J. van der Horst-BruinsmaI.E. de KoningM.H. HabibuwM.R. DijkmansB.A. Simultaneous development of acute phase response and autoantibodies in preclinical rheumatoid arthritis.Ann. Rheum. Dis.200665453553710.1136/ard.2005.04065916079166
    [Google Scholar]
  67. SongY.W. KangE.H. Autoantibodies in rheumatoid arthritis: rheumatoid factors and anticitrullinated protein antibodies.QJM2010103313914610.1093/qjmed/hcp16519926660
    [Google Scholar]
  68. ChandranU. MehendaleN. PatilS. ChaguturuR. PatwardhanB. Network Pharmacology.Innovative Approaches in Drug Discovery.Elsevier201712716410.1016/B978‑0‑12‑801814‑9.00005‑2
    [Google Scholar]
  69. GrilletB. PereiraR.V.S. Van DammeJ. Abu El-AsrarA. ProostP. OpdenakkerG. Matrix metalloproteinases in arthritis: towards precision medicine.Nat. Rev. Rheumatol.202319636337710.1038/s41584‑023‑00966‑w37161083
    [Google Scholar]
  70. TanakitA. RouffetM. MartinD.P. CohenS.M. Investigating chelating sulfonamides and their use in metalloproteinase inhibitors.Dalton Trans.201241216507651510.1039/c2dt12373h22411188
    [Google Scholar]
  71. GuptaS. SinghN. KhanT. JoshiS. Thiosemicarbazone derivatives of transition metals as multi-target drugs: A review.Results in Chemistry2022410045910.1016/j.rechem.2022.100459
    [Google Scholar]
  72. DavidJ. Compositions and methods for inhibition of cathepsins.Patent US9873668B2, 2015.
  73. ParkerE.N. SongJ. Kishore KumarG.D. OdutolaS.O. ChavarriaG.E. Charlton-SevcikA.K. StreckerT.E. BarnesA.L. SudhanD.R. WittenbornT.R. SiemannD.W. HorsmanM.R. ChaplinD.J. TrawickM.L. PinneyK.G. Synthesis and biochemical evaluation of benzoylbenzophenone thiosemicarbazone analogues as potent and selective inhibitors of cathepsin L.Bioorg. Med. Chem.201523216974699210.1016/j.bmc.2015.09.03626462052
    [Google Scholar]
  74. ZaidA. GérardinP. TaylorA. MostafaviH. MalvyD. MahalingamS. Review: Chikungunya arthritis: implications of acute and chronic inflammation mechanisms on disease management.Arthritis Rheumatol.201870448449510.1002/art.4040329287308
    [Google Scholar]
  75. AmaralJ.K. BilsborrowJ.B. SchoenR.T. Chronic chikungunya arthritis and rheumatoid arthritis: What they have in common.Am. J. Med.20201333e91e9710.1016/j.amjmed.2019.10.00531705850
    [Google Scholar]
  76. IzumidaM. HayashiH. TanakaA. KuboY. CathepsinB. Cathepsin B protease facilitates chikungunya virus envelope protein-mediated infection via endocytosis or macropinocytosis.Viruses202012772210.3390/v1207072232635194
    [Google Scholar]
  77. AghdassiA.A. JohnD.S. SendlerM. WeissF.U. ReinheckelT. MayerleJ. LerchM.M. CathepsinD. Cathepsin D regulates cathepsin B activation and disease severity predominantly in inflammatory cells during experimental pancreatitis.J. Biol. Chem.201829331018102910.1074/jbc.M117.81477229229780
    [Google Scholar]
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  • Article Type:
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Keyword(s): Arthritis; in vivo; inflammation; MBZM-N-IBT; molecular docking; network pharmacology
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