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Volume 21, Issue 19
  • ISSN: 1570-1808
  • E-ISSN: 1875-628X

Abstract

Introduction

Increased resistance of () poses a significant threat to disease control in animal husbandry and human public health. Eukaryotic-like Ser / Thr phosphatase (Stp1) is an effective target for the regulation of bacterial virulence. In this study, potential Stp1 inhibitors were screened through virtual screening, and the inhibitory mechanism of these compounds was explored using molecular dynamics simulations.

Methods

Virtual screening studies were performed using AutoDock vina 4.0 software. The SwissADME server predicted the properties of chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET). Molecular dynamics simulation was performed using the Gromacs software package, and molecular mechanics/generalized Born surface area (MM/GBSA) was calculated using the Amber 10 package. The inhibition mechanism was verified using phosphatase, mutagenesis, and fluorescence quenching assays.

Results

The 2-methylvaleric acid from foods was found to be a competitive inhibitor of Stp1, based on the kinetics of the enzymatic reaction and virtual screening. Molecular dynamics simulations revealed that 2-methylvaleric acid binds to the active center of Stp1 and reduces enzyme activity by competing with its substrate. Interestingly, the molecular modeling and kinetics of the enzymatic reactions were consistent. Energy decomposition indicated that Met39, Thr102, Ile164, Val167, and Thr170 played important roles in complex binding. Additionally, the SwissADME server showed that 2-methylvaleric acid possesses drug-like properties.

Conclusion

Therefore, 2-methylvaleric acid is a promising compound for further exploration because of its potential to reduce virulence. These findings are conducive to additional discovery and design of new inhibitors.

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2025-07-09

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References

  1. LiuG. PangB. LiN. JinH. LiJ. WuW. AiC. JiangC. ShiJ. Therapeutic effect of Lactobacillus rhamnosus SHA113 on intestinal infection by multi-drug-resistant Staphylococcus aureus and its underlying mechanisms.Food Funct.20201176226623910.1039/D0FO00969E 32589178
     [Google Scholar]
  2. BaiJ.R. ZhongK. WuY.P. ElenaG. GaoH. Antibiofilm activity of shikimic acid against Staphylococcus aureus.Food Control20199532733310.1016/j.foodcont.2018.08.020
     [Google Scholar]
  3. HammoudaM. SadatA. AwadA. Prevalence of Staphylococcus aureus in The food Chain, Humans, and The environment in Mansoura. Egypt.J. Vet. Sci.202456342743510.21608/ejvs.2024.267600.1832
     [Google Scholar]
  4. SheetO.H. Al-MahmoodO.A. TahaA.H. AlsanjaryR.A. PlötzM. AbdulmawjoodA.A. Molecular detection of methicillin-resistant Staphylococcus aureus isolated from foods in Germany using LAMP assay.Egypt. J. Vet. Sci.20255661153116010.21608/ejvs.2024.281105.1981
     [Google Scholar]
  5. ShresthaN.K. FraserT.G. GordonS.M. Methicillin resistance in Staphylococcus aureus infections among patients colonized with methicillin-susceptible Staphylococcus aureus.Clin. Microbiol. Infect.2019251717510.1016/j.cmi.2018.03.045 29649598
     [Google Scholar]
  6. LeiZ. ZhangD. LuB. ZhouW. WangD. Activation of mast cells in skin abscess induced by Staphylococcus aureus (S. aureus) infection in mice.Res. Vet. Sci.2018118667110.1016/j.rvsc.2018.01.016 29421486
     [Google Scholar]
  7. TongZ. ChenZ. LiZ. XieZ. ZhangH. Mechanisms of promoting the differentiation and bone resorption function of osteoclasts by Staphylococcus aureus infection.Int. J. Med. Microbiol.2022312715156810.1016/j.ijmm.2022.151568 36240531
     [Google Scholar]
  8. YeC. WangZ. HuY. DengC. LiaoL. SunL. WangC. Systematic review and meta-analysis of the efficacy and safety of vancomycin combined with β-lactam antibiotics in the treatment of methicillin-resistant Staphylococcus aureus bloodstream infections.J. Glob. Antimicrob. Resist.20202330331010.1016/j.jgar.2020.09.024 33045437
     [Google Scholar]
  9. Abu OthmanA. HumphreysH. O’NeillE. Fitzgerald-HughesD. Differences in expression of virulence genes amongst invasive and colonizing isolates of meticillin-resistant Staphylococcus aureus.J. Med. Microbiol.201160225926110.1099/jmm.0.019174‑0 20965917
     [Google Scholar]
  10. MechessoA.F. MoonD.C. RyooG.S. SongH.J. ChungH.Y. KimS.U. ChoiJ.H. KimS.J. KangH.Y. NaS.H. YoonS.S. LimS.K. Resistance profiling and molecular characterization of Staphylococcus aureus isolated from goats in Korea.Int. J. Food Microbiol.202133610890110.1016/j.ijfoodmicro.2020.108901 33075694
     [Google Scholar]
  11. SongM. TangQ. DingY. TanP. ZhangY. WangT. ZhouC. XuS. LyuM. BaiY. MaX. Staphylococcus aureus and biofilms: Transmission, threats, and promising strategies in animal husbandry.J. Anim. Sci. Biotechnol.20241514410.1186/s40104‑024‑01007‑6 38475886
     [Google Scholar]
  12. O’DeaM. AbrahamR.J. SahibzadaS. LeeT. JordanD. LairdT. PangS. BullerN. SteggerM. CoombsG.W. TrottD.J. AbrahamS. Antimicrobial resistance and genomic insights into bovine mastitis-associated Staphylococcus aureus in Australia.Vet. Microbiol.202025010885010.1016/j.vetmic.2020.108850 33011663
     [Google Scholar]
  13. BatchelderJ.I. TaylorA.J. MokW.W.K. Metabolites augment oxidative stress to sensitize antibiotic-tolerant Staphylococcus aureus to fluoroquinolones.MBio20241512e027142410.1128/mbio.02714‑24 39475229
     [Google Scholar]
  14. GuoY. SongG. SunM. WangJ. WangY. Prevalence and therapies of antibiotic-resistance in Staphylococcus aureus.Front. Cell. Infect. Microbiol.20201010710.3389/fcimb.2020.00107 32257966
     [Google Scholar]
  15. LiX. HouY. ZouH. WangY. XuY. WangL. WangB. YanM. LengX. Unraveling the efficacy of verbascoside in thwarting MRSA pathogenicity by targeting sortase A.Appl. Microbiol. Biotechnol.2024108136010.1007/s00253‑024‑13202‑6 38836914
     [Google Scholar]
  16. DengW. XueR.Y. XiaoS.X. WangJ.T. LiaoX.W. YuR.J. XiongY.S. Discovery of quaternized pyridine-thiazole-ruthenium complexes as potent anti-Staphylococcus aureus agents.Eur. J. Med. Chem.202427711671210.1016/j.ejmech.2024.116712 39106657
     [Google Scholar]
  17. OliveiraD. BorgesA. SimõesM. Staphylococcus aureus toxins and their molecular activity in infectious diseases.Toxins (Basel)201810625210.3390/toxins10060252 29921792
     [Google Scholar]
  18. OttoM. Staphylococcus aureus toxins.Curr. Opin. Microbiol.201417323710.1016/j.mib.2013.11.004 24581690
     [Google Scholar]
  19. ZhengW. CaiX. XieM. LiangY. WangT. LiZ. Structure-based identification of a potent inhibitor targeting Stp1-mediated virulence regulation in Staphylococcus aureus.Cell Chem. Biol.20162381002101310.1016/j.chembiol.2016.06.014 27499528
     [Google Scholar]
  20. YangT. LiuT. GanJ. YuK. ChenK. XueW. LanL. YangS. YangC.G. Structural insight into the mechanism of Staphylococcus aureus Stp1 phosphatase.ACS Infect. Dis.20195684185010.1021/acsinfecdis.8b00316 30868877
     [Google Scholar]
  21. OhlsenK. DonatS. The impact of serine/threonine phosphorylation in Staphylococcus aureus.Int. J. Med. Microbiol.20103002-313714110.1016/j.ijmm.2009.08.016 19783479
     [Google Scholar]
  22. CameronD.R. WardD.V. KostouliasX. HowdenB.P. MoelleringR.C.Jr EliopoulosG.M. PelegA.Y. Serine/threonine phosphatase Stp1 contributes to reduced susceptibility to vancomycin and virulence in Staphylococcus aureus.J. Infect. Dis.2012205111677168710.1093/infdis/jis252 22492855
     [Google Scholar]
  23. ZhengW. LiangY. ZhaoH. ZhangJ. LiZ. 5,5′‐Methylenedisalicylic Acid (MDSA) Modulates SarA/MgrA Phosphorylation by Targeting Ser/Thr Phosphatase Stp1.ChemBioChem20151671035104010.1002/cbic.201500003 25810089
     [Google Scholar]
  24. ApiA.M. BelsitoD. BotelhoD. BruzeM. BurtonG.A.Jr BuschmannJ. DagliM.L. DateM. DekantW. DeodharC. FrancisM. FryerA.D. JonesL. JoshiK. La CavaS. LapczynskiA. LieblerD.C. O’BrienD. PatelA. PenningT.M. RitaccoG. RomineJ. SadekarN. SalvitoD. SchultzT.W. SipesI.G. SullivanG. ThakkarY. TokuraY. TsangS. RIFM fragrance ingredient safety assessment, 2-Methylvaleric acid, CAS Registry Number 97-61-0.Food Chem. Toxicol.2018118Suppl. 1S59S6810.1016/j.fct.2018.06.034 29935244
     [Google Scholar]
  25. MaharjanR. GyawaliK. AcharyaA. KhanalM. GhimireM.P. LamichhaneT.R. Artemisinin derivatives as potential drug candidates against Mycobacterium tuberculosis: Insights from molecular docking, MD simulations, PCA, MM/GBSA and ADMET analysis.Mol. Simul.2024501171772810.1080/08927022.2024.2346525
     [Google Scholar]
  26. SeeligerD. de GrootB.L. Ligand docking and binding site analysis with PyMOL and Autodock/Vina.J. Comput. Aided Mol. Des.201024541742210.1007/s10822‑010‑9352‑6 20401516
     [Google Scholar]
  27. HelgrenT.R. HagenT.J. Demonstration of autodock as an educational tool for drug discovery.J. Chem. Educ.201794334534910.1021/acs.jchemed.6b00555 28670004
     [Google Scholar]
  28. SterlingT. IrwinJ.J. ZINC 15 – ligand discovery for everyone.J. Chem. Inf. Model.201555112324233710.1021/acs.jcim.5b00559 26479676
     [Google Scholar]
  29. DalalV. DhankharP. SinghV. SinghV. RakhaminovG. Golemi-KotraD. KumarP. Structure-based identification of potential drugs against FmtA of Staphylococcus aureus: Virtual screening, molecular dynamics, MM-GBSA, and QM/MM.Protein J.202140214816510.1007/s10930‑020‑09953‑6 33421024
     [Google Scholar]
  30. AmraniL. Nekounam GhadirliR. Abu BakarU. GuendouziA. BelkhiriL. AzmanA.S. HassandarvishP. Elanie KhairatJ. In silico evaluation of the anti-influenza potential of Streptomyces bioactive compounds.J. Taibah Univ. Sci.2024181241842910.1080/16583655.2024.2418429
     [Google Scholar]
  31. KumariR. RathiR. PathakS.R. DalalV. Structural-based virtual screening and identification of novel potent antimicrobial compounds against YsxC of Staphylococcus aureus.J. Mol. Struct.2022125513247610.1016/j.molstruc.2022.132476
     [Google Scholar]
  32. ChenT. ShuX. ZhouH. BeckfordF.A. MisirM. Algorithm selection for protein–ligand docking: Strategies and analysis on ACE.Sci. Rep.2023131821910.1038/s41598‑023‑35132‑5 37217655
     [Google Scholar]
  33. AgboolaO.E. AyinlaZ.A. AgboolaS.S. AdegbuyiT.A. AkinseyeJ.F. SijuadeA. EgbebiA.H. IlesanmiO.S. AgboolaA.A. IbrahimO.K. Molecular mechanisms underlying the erectogenic effects of nutraceutical lunamarine, a novel PDE5 inhibitor derived from watermelon (Citrullus lanatus).Discover Food20244115310.1007/s44187‑024‑00233‑1
     [Google Scholar]
  34. XueQ. LiuX. RussellP. LiJ. PanW. FuJ. ZhangA. Evaluation of the binding performance of flavonoids to estrogen receptor alpha by Autodock, Autodock Vina and Surflex-Dock.Ecotoxicol. Environ. Saf.202223311332310.1016/j.ecoenv.2022.113323 35183811
     [Google Scholar]
  35. Afroj ZinniaM. Khademul IslamA.B.M.M. Delineating potential de novo therapeutics and repurposed drugs against novel protein LRRC15 to treat SARS-CoV-2.Lett. Drug Des. Discov.20242191502152010.2174/1570180820666230223120829
     [Google Scholar]
  36. GhasemaliS. FarajniaS. NazariA. BargahiN. MohammadinasrM. Molecular docking, molecular dynamics simulation, and analysis of EGFR-derived peptides against the EGF.Lett. Drug Des. Discov.20242171240125110.2174/1570180820666230224100942
     [Google Scholar]
  37. SolimanA.Q.S. Abdel-LatifS.A. Abdel-KhalikS. AbbasS.M. AhmedO.M. Design, synthesis, structural characterization, molecular docking, antibacterial, anticancer activities, and density functional theory calculations of novel MnII, CoII, NiII, and CuII complexes based on pyrazolone-sulfadiazine azo-dye ligand.J. Mol. Struct.2024131813940210.1016/j.molstruc.2024.139402
     [Google Scholar]
  38. SertY. Al-WahaibiL.H. GökceH. HassanH.M. AlsfoukA. El-EmamA.A. Molecular docking, Hirshfeld surface analysis and spectroscopic investigations of 1-(adamantan-1-yl)-3-(4-fluorophenyl)thiourea: A potential bioactive agent.Chem. Phys. Lett.201973513676210.1016/j.cplett.2019.136762
     [Google Scholar]
  39. YuY. WangX. GaoY. YangY. WangG. SunL. ZhouY. NiuX. Insight into the catalytic hydrolysis mechanism of New Delhi metallo-β-lactamase to aztreonam by molecular modeling.J. Mol. Liq.201928224425010.1016/j.molliq.2019.03.006
     [Google Scholar]
  40. DangQ. WuD. LiY. FangL. LiuC. WangX. LiuX. MinW. Walnut-derived peptides ameliorate d-galactose-induced memory impairments in a mouse model via inhibition of MMP-9- mediated blood–brain barrier disruption. Food Res. Int.,2022162Pt A11202910.1016/j.foodres.2022.11202936461249
     [Google Scholar]
  41. ShowalterS.A. BrüschweilerR. Validation of molecular dynamics simulations of biomolecules using NMR spin relaxation as benchmarks: Application to the AMBER99SB force field.J. Chem. Theory Comput.20073396197510.1021/ct7000045 26627416
     [Google Scholar]
  42. YanL.M. SunC. LiuH.T. Opposite phenomenon to the flying ice cube in molecular dynamics simulations of flexible TIP3P water.Adv. Manuf.20131216016510.1007/s40436‑013‑0024‑3
     [Google Scholar]
  43. dos Santos NascimentoI.J. de AquinoT.M. da Silva JúniorE.F. de MouraR.O. Insights on microsomal prostaglandin E2 synthase 1 (mPGES-1) inhibitors using molecular dynamics and MM/PBSA calculations.Lett. Drug Des. Discov.20242161033104710.2174/1570180820666230228105833
     [Google Scholar]
  44. KarakurtT. CukurovaliA. SubasiN.T. OnaranA. EceA. EkerS. KaniI. Experimental and theoretical studies on tautomeric structures of a newly synthesized 2,2′(hydrazine-1,2-diylidenebis(propan-1-yl-1-ylidene))diphenol.Chem. Phys. Lett.201869313214510.1016/j.cplett.2018.01.016
     [Google Scholar]
  45. Neves CruzJ. da CostaK.S. de CarvalhoT.A.A. de AlencarN.A.N. Measuring the structural impact of mutations on cytochrome P450 21A2, the major steroid 21-hydroxylase related to congenital adrenal hyperplasia.J. Biomol. Struct. Dyn.20203851425143410.1080/07391102.2019.1607560 30982438
     [Google Scholar]
  46. MetwalyA.M. El-FakharanyE.M. AlsfoukA.A. IbrahimI.M. ElkaeedE.B. EissaI.H. Integrated study of Quercetin as a potent SARS-CoV-2 RdRp inhibitor: Binding interactions, MD simulations, and in vitro assays.PLoS One20241912e031286610.1371/journal.pone.0312866 39625895
     [Google Scholar]
  47. DainaA. MichielinO. ZoeteV. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules.Sci. Rep.2017714271710.1038/srep42717 28256516
     [Google Scholar]
  48. KhanS. KhatriD.K. In-silico screening to identify phytochemical inhibitor for hP2X7: A crucial inflammatory cell death mediator in Parkinson’s disease.Comput. Biol. Chem.202511510828510.1016/j.compbiolchem.2024.108285 39615401
     [Google Scholar]
  49. DainaA. MichielinO. ZoeteV. iLOGP: A simple, robust, and efficient description of n-octanol/water partition coefficient for drug design using the GB/SA approach.J. Chem. Inf. Model.201454123284330110.1021/ci500467k 25382374
     [Google Scholar]
  50. LvH. ZhuZ. QianC. LiT. HanZ. ZhangW. SiX. WangJ. DengX. LiL. FangT. XiaJ. WuS. ZhouY. Discovery of isatin-β-methyldithiocarbazate derivatives as New Delhi metallo- β-lactamase-1 (NDM-1) inhibitors against NDM-1 producing clinical isolates.Biomed. Pharmacother.202316611543910.1016/j.biopha.2023.115439 37673020
     [Google Scholar]
  51. WangJ. ZhouX. LiW. DengX. DengY. NiuX. Curcumin protects mice from Staphylococcus aureus pneumonia by interfering with the self-assembly process of α-hemolysin.Sci. Rep.2016612825410.1038/srep28254 27345357
     [Google Scholar]
  52. SongY. ZouY. XuL. WangJ. DengX. ZhouY. LiD. Ginkgolic Acid as a carbapenem synergist against KPC-2 positive Klebsiella pneumoniae.Front. Microbiol.202415142660310.3389/fmicb.2024.1426603 39234551
     [Google Scholar]
  53. XuL. ZhouY. NiuS. LiuZ. ZouY. YangY. FengH. LiuD. NiuX. DengX. WangY. WangJ. A novel inhibitor of monooxygenase reversed the activity of tetracyclines against tet(X3)/tet(X4)-positive bacteria.EBioMedicine20227810394310.1016/j.ebiom.2022.103943 35306337
     [Google Scholar]
  54. XieP. GaoY. WuC. LiX. YangY. The inhibitory mechanism of echinacoside against Staphylococcus aureus Ser/Thr phosphatase Stp1 by virtual screening and molecular modeling.J. Mol. Model.2023291032010.1007/s00894‑023‑05723‑0 37725157
     [Google Scholar]
  55. YangY. WangX. GaoY. WangH. NiuX. Insight into the Dual inhibitory Mechanism of verbascoside targeting serine/threonine phosphatase Stp1 against Staphylococcus aureus.Eur. J. Pharm. Sci.202115710562810.1016/j.ejps.2020.105628 33115673
     [Google Scholar]
  56. BudaevaV.V. SkibaE.A. BaibakovaO.V. MakarovaE.I. OrlovS.E. KukhlenkoA.A. UdoratinaE.V. ShcherbakovaT.P. KuchinA.V. SakovichG.V. Kinetics of the enzymatic hydrolysis of lignocellulosic materials at different concentrations of the substrate.Catal. Ind.20168818710.1134/S2070050416010025
     [Google Scholar]
  57. KaurS. KaurK. JindalJ. GillG.K. Characterization and inhibition kinetics of gut α-amylase from Chilo partellus through Lineweaver- Burk, fractional velocity and combination plots.Int. J. Trop. Insect Sci.20234361987200010.1007/s42690‑023‑01101‑8
     [Google Scholar]
  58. DongJ. QiuJ. ZhangY. LuC. DaiX. WangJ. LiH. WangX. TanW. LuoM. NiuX. DengX. Oroxylin A inhibits hemolysis via hindering the self-assembly of α-hemolysin heptameric transmembrane pore.PLOS Comput. Biol.201391e100286910.1371/journal.pcbi.1002869 23349625
     [Google Scholar]
  59. ShengQ. WangN. ZhouY. DengX. HouX. WangJ. QiuJ. DengY. A new function of thymol nanoemulsion for reversing colistin resistance in Salmonella enterica serovar Typhimurium infection.J. Antimicrob. Chemother.202378122983299410.1093/jac/dkad342 37923362
     [Google Scholar]
  60. EftinkM.R. GhironC.A. Fluorescence quenching studies with proteins.Anal. Biochem.1981114219922710.1016/0003‑2697(81)90474‑7 7030122
     [Google Scholar]
  61. LiuM. LvQ. XuJ. LiuB. ZhouY. ZhangS. ShenX. WangL. Isoflavone glucoside genistin, an inhibitor targeting Sortase A and Listeriolysin O, attenuates the virulence of Listeria monocytogenes in vivo and in vitro.Biochem. Pharmacol.202320911544710.1016/j.bcp.2023.115447 36746262
     [Google Scholar]
  62. ZhouY. GuoY. SunX. DingR. WangY. NiuX. WangJ. DengX. Application of oleanolic acid and its analogues in combating pathogenic bacteria in vitro/vivo by a two-pronged strategy of β-lactamases and hemolysins.ACS Omega2020520114241143810.1021/acsomega.0c00460 32478231
     [Google Scholar]
  63. CamussoneC.M. ReidelI.G. MolineriA.I. CicotelloJ. MiottiC. Suarez ArchillaG.A. CurtiC.C. VeauteC. CalvinhoL.F. Efficacy of immunization with a recombinant S. aureus vaccine formulated with liposomes and ODN-CpG against natural S. aureus intramammary infections in heifers and cows.Res. Vet. Sci.202214517718710.1016/j.rvsc.2022.02.014 35219182
     [Google Scholar]
  64. ThapaliyaD. KadariyaJ. CapuanoM. RushH. YeeC. OetM. LohaniS. SmithT.C. Prevalence and molecular characterization of Staphylococcus aureus and Methicillin-resistant S. aureus on children’s playgrounds.Pediatr. Infect. Dis. J.2019383e43e4710.1097/INF.0000000000002095 29746375
     [Google Scholar]
  65. WangQ. YangQ. Seizing the hidden assassin: Current detection strategies for Staphylococcus aureus and methicillin-resistant S. aureus.J. Agric. Food Chem.20247230165691658210.1021/acs.jafc.4c02421 39031091
     [Google Scholar]
  66. KumariR. DalalV. Identification of potential inhibitors for LLM of Staphylococcus aureus: Structure-based pharmacophore modeling, molecular dynamics, and binding free energy studies.J. Biomol. Struct. Dyn.202240209833984710.1080/07391102.2021.1936179 34096457
     [Google Scholar]
  67. KumarP. DalalV. KotraD.G. KumarP. In-silico approach to identify novel potent inhibitors against GraR of S aureus.Front. Biosci.20202571337136010.2741/4859 32114436
     [Google Scholar]
  68. BaothmanO.A. IslamM.R. Exploring breast cancer treatment paradigms: Innovative design, molecular docking and dynamic simulation of LOXL2 inhibitors.Mol. Simul.2024501063164310.1080/08927022.2024.2333907
     [Google Scholar]
  69. LillM.A. DanielsonM.L. Computer-aided drug design platform using PyMOL.J. Comput. Aided Mol. Des.2011251131910.1007/s10822‑010‑9395‑8 21053052
     [Google Scholar]
  70. DalalV. KumariR. Screening and identification of natural product‐like compounds as potential antibacterial agents targeting FemC of Staphylococcus aureus: An in‐silico approach.ChemistrySelect2022742e20220172810.1002/slct.202201728
     [Google Scholar]
  71. Neves CruzJ. Santana de OliveiraM. Gomes SilvaS. Pedro da Silva Souza FilhoA. Santiago PereiraD. Lima e LimaA.H. de Aguiar AndradeE.H. Insight into the interaction mechanism of nicotine, NNK, and NNN with cytochrome P450 2A13 based on molecular dynamics simulation.J. Chem. Inf. Model.202060276677610.1021/acs.jcim.9b00741 31622091
     [Google Scholar]
  72. WallaceA.C. LaskowskiR.A. ThorntonJ.M. LIGPLOT: A program to generate schematic diagrams of protein-ligand interactions.Protein Eng. Des. Sel.19958212713410.1093/protein/8.2.127 7630882
     [Google Scholar]
  73. FengZ. LuX. GanL. ZhangQ. LinL. Xanthones, a promising anti-inflammatory scaffold: Structure, activity, and drug likeness analysis.Molecules202025359810.3390/molecules25030598 32019180
     [Google Scholar]
  74. CetinA. In silico studies on stilbenolignan analogues as SARS-CoV-2 Mpro inhibitors.Chem. Phys. Lett.202177113856310.1016/j.cplett.2021.138563 33776065
     [Google Scholar]
  75. OsoB.J. AdeoyeA.O. OlaoyeI.F. Pharmacoinformatics and hypothetical studies on allicin, curcumin, and gingerol as potential candidates against COVID-19-associated proteases.J. Biomol. Struct. Dyn.202240138940010.1080/07391102.2020.1813630 32876538
     [Google Scholar]
  76. EnmozhiS.K. RajaK. SebastineI. JosephJ. Andrographolide as a potential inhibitor of SARS-CoV-2 main protease: An in silico approach.J. Biomol. Struct. Dyn.20203991710.1080/07391102.2020.1760136 32329419
     [Google Scholar]
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The Mechanism of 2-Methyl Valeric Acid Inhibiting Virulence Regulator Ser/Thr Phosphatase (Stp1) in Staphylococcus aureus
Letters in Drug Design & Discovery 21, 4870 (2024); https://doi.org/10.2174/0115701808349595241231062530
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  • Article Type:     Research Article
Keyword(s): 2-methylvaleric acid; molecular docking; molecular dynamics simulations; Ser/Thr phosphatase (Stp1); Staphylococcus aureus; virtual screening

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