*Result*: In Silico Prediction of Potential pTLR7/pSTING Dual-Targeting Ligands via Virtual Screening and Molecular Dynamics Simulation.
Title:
In Silico Prediction of Potential pTLR7/pSTING Dual-Targeting Ligands via Virtual Screening and Molecular Dynamics Simulation.
Authors:
Liu C; Key Laboratory of New Animal Drug of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Science of Chinese Academy Agriculture Sciences, Lanzhou 730050, China., Qin Z; Key Laboratory of New Animal Drug of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Science of Chinese Academy Agriculture Sciences, Lanzhou 730050, China., Bai L; Key Laboratory of New Animal Drug of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Science of Chinese Academy Agriculture Sciences, Lanzhou 730050, China., Xu X; Key Laboratory of New Animal Drug of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Science of Chinese Academy Agriculture Sciences, Lanzhou 730050, China., Ge W; Key Laboratory of New Animal Drug of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Science of Chinese Academy Agriculture Sciences, Lanzhou 730050, China., Li Z; Key Laboratory of New Animal Drug of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Science of Chinese Academy Agriculture Sciences, Lanzhou 730050, China., Li J; Key Laboratory of New Animal Drug of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Science of Chinese Academy Agriculture Sciences, Lanzhou 730050, China.
Source:
International journal of molecular sciences [Int J Mol Sci] 2025 Dec 28; Vol. 27 (1). Date of Electronic Publication: 2025 Dec 28.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
Imprint Name(s):
Original Publication: Basel, Switzerland : MDPI, [2000-
MeSH Terms:
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J Hematol Oncol. 2022 Oct 8;15(1):142. (PMID: 36209176)
Cells. 2023 Jul 15;12(14):. (PMID: 37508526)
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Chin J Nat Med. 2023 Nov;21(11):852-858. (PMID: 38035940)
Trends Cell Biol. 2023 Mar;33(3):189-203. (PMID: 35931610)
Comput Biol Med. 2022 Jun;145:105517. (PMID: 35585729)
Nano Res. 2022;15(7):6328-6339. (PMID: 35464625)
Bioorg Chem. 2024 Jul;148:107451. (PMID: 38759357)
Food Res Int. 2024 Aug;190:114653. (PMID: 38945587)
Int J Mol Sci. 2022 May 11;23(10):. (PMID: 35628179)
Eur J Med Chem. 2023 Jan 15;246:114943. (PMID: 36462438)
Cell Chem Biol. 2023 Nov 16;30(11):1366-1376.e7. (PMID: 37536341)
Int J Mol Sci. 2023 Jun 20;24(12):. (PMID: 37373516)
J Virol. 2023 Feb 28;97(2):e0192322. (PMID: 36779759)
Brief Bioinform. 2022 May 13;23(3):. (PMID: 35395683)
J Med Chem. 2021 Jun 10;64(11):7507-7532. (PMID: 34048243)
Molecules. 2023 Apr 03;28(7):. (PMID: 37049948)
Mol Pharm. 2018 Nov 5;15(11):4933-4946. (PMID: 30281314)
Viruses. 2022 May 02;14(5):. (PMID: 35632696)
Nat Commun. 2020 Oct 15;11(1):5204. (PMID: 33060576)
Int Immunol. 2016 May;28(5):211-22. (PMID: 26489884)
J Comput Chem. 2003 Oct;24(13):1549-62. (PMID: 12925999)
J Med Chem. 2020 May 14;63(9):4776-4789. (PMID: 32302115)
Hepatology. 2005 Sep;42(3):724-31. (PMID: 16116638)
Eur J Med Chem. 2021 Jan 15;210:112978. (PMID: 33189437)
Science. 2004 Mar 5;303(5663):1529-31. (PMID: 14976261)
Cancers (Basel). 2022 Dec 11;14(24):. (PMID: 36551577)
Mol Immunol. 2008 Jun;45(11):3238-43. (PMID: 18439678)
Proc Natl Acad Sci U S A. 2023 Aug 15;120(33):e2305420120. (PMID: 37549268)
Int J Mol Sci. 2019 Feb 18;20(4):. (PMID: 30781686)
Org Biomol Chem. 2019 Feb 13;17(7):1869-1874. (PMID: 30117503)
J Clin Invest. 2020 Apr 1;130(4):1635-1652. (PMID: 31874109)
Clin Infect Dis. 2021 Jun 1;72(11):e815-e824. (PMID: 33043969)
J Control Release. 2022 Jul;347:356-368. (PMID: 35569585)
J Immunother. 2026 Jan 01;49(1):1-14. (PMID: 40765175)
J Immunother Cancer. 2022 Oct;10(10):. (PMID: 36253000)
Bioorg Chem. 2023 Jun;135:106504. (PMID: 37015153)
Proc Natl Acad Sci U S A. 2021 Jun 15;118(24):. (PMID: 34099558)
Front Pharmacol. 2022 Apr 26;13:896434. (PMID: 35559247)
Science. 2004 Mar 5;303(5663):1526-9. (PMID: 14976262)
J Biol Chem. 2019 Jul 26;294(30):11420-11432. (PMID: 31167783)
Eur J Med Chem. 2017 Aug 18;136:195-211. (PMID: 28494256)
Front Immunol. 2024 Oct 31;15:1432846. (PMID: 39544933)
J Med Chem. 2021 Feb 11;64(3):1649-1669. (PMID: 33470814)
Proc Natl Acad Sci U S A. 2022 Dec 6;119(49):e2214278119. (PMID: 36442099)
Nature. 2018 Dec;564(7736):439-443. (PMID: 30405246)
Bioorg Chem. 2023 Feb;131:106300. (PMID: 36455484)
Clin Transl Med. 2021 Jan;11(1):e266. (PMID: 33463061)
ACS Chem Biol. 2013 Jul 19;8(7):1396-401. (PMID: 23683494)
Sci Rep. 2019 Apr 11;9(1):5917. (PMID: 30976083)
Immunity. 2016 Oct 18;45(4):737-748. (PMID: 27742543)
BMC Complement Med Ther. 2022 Feb 5;22(1):36. (PMID: 35123452)
Drug Discov Today. 2003 Jan 1;8(1):12-6. (PMID: 12546981)
Nat Rev Mol Cell Biol. 2020 Sep;21(9):501-521. (PMID: 32424334)
J Cell Biochem. 2017 Dec;118(12):4222-4229. (PMID: 28419514)
ACS Omega. 2016 Dec 31;1(6):1081-1103. (PMID: 30023502)
Curr Neuropharmacol. 2024;22(13):2168-2190. (PMID: 38847378)
Food Res Int. 2023 Sep;171:112982. (PMID: 37330840)
Virulence. 2022 Dec;13(1):740-756. (PMID: 35437104)
J Cheminform. 2019 Aug 30;11(1):58. (PMID: 33430989)
Sci Rep. 2017 Mar 03;7:42717. (PMID: 28256516)
Front Immunol. 2024 Mar 12;15:1353336. (PMID: 38533502)
Int J Biol Macromol. 2020 Oct 1;160:1-17. (PMID: 32470577)
Biomed Pharmacother. 2023 Nov;167:115458. (PMID: 37699319)
ACS Cent Sci. 2022 Oct 26;8(10):1435-1446. (PMID: 36313164)
Comput Biol Med. 2022 Jul;146:105549. (PMID: 35751193)
J Transl Med. 2024 Jan 21;22(1):86. (PMID: 38246999)
J Exp Med. 2024 Feb 5;221(2):. (PMID: 38095631)
Front Immunol. 2022 Jan 13;12:814709. (PMID: 35095914)
Cell Rep Med. 2023 May 16;4(5):101036. (PMID: 37196635)
Trends Parasitol. 2020 Sep;36(9):773-784. (PMID: 32736985)
Cell Rep. 2018 Dec 18;25(12):3405-3421.e7. (PMID: 30566866)
Chem Biol Interact. 2022 Mar 1;355:109838. (PMID: 35123995)
J Mol Struct. 2021 Sep 5;1239:130488. (PMID: 33903778)
J Mol Struct. 2023 Jul 15;1284:135409. (PMID: 36993878)
Nucleic Acids Res. 2021 Jul 2;49(W1):W5-W14. (PMID: 33893803)
RSC Med Chem. 2023 Mar 27;14(6):1101-1113. (PMID: 37360395)
Int J Mol Sci. 2024 May 30;25(11):. (PMID: 38892186)
J Enzyme Inhib Med Chem. 2022 Dec;37(1):616-628. (PMID: 35067136)
J Exp Med. 2021 Nov 1;218(11):. (PMID: 34473195)
Acta Pharm Sin B. 2014 Dec;4(6):430-7. (PMID: 26579414)
Acta Crystallogr D Biol Crystallogr. 2013 Mar;69(Pt 3):352-66. (PMID: 23519410)
Front Immunol. 2024 Feb 15;15:1352479. (PMID: 38426093)
Int J Mol Sci. 2023 Feb 28;24(5):. (PMID: 36902093)
PLoS Pathog. 2024 Apr 15;20(4):e1012136. (PMID: 38620034)
Eur J Med Chem. 2022 Nov 5;241:114627. (PMID: 35963129)
J Enzyme Inhib Med Chem. 2022 Dec;37(1):333-338. (PMID: 34979838)
J Ethnopharmacol. 2024 Oct 28;333:118472. (PMID: 38901681)
Trends Pharmacol Sci. 2024 Jul;45(7):628-638. (PMID: 38853102)
Nat Nanotechnol. 2022 Aug;17(8):891-899. (PMID: 35637356)
Cell Death Dis. 2024 Apr 15;15(4):267. (PMID: 38622131)
Mol Pharm. 2022 Sep 5;19(9):3228-3241. (PMID: 35904247)
Biomed Pharmacother. 2022 Mar;147:112622. (PMID: 35008000)
Eur J Med Chem. 2024 Mar 5;267:116179. (PMID: 38340509)
J Hematol Oncol. 2022 Oct 8;15(1):142. (PMID: 36209176)
Cells. 2023 Jul 15;12(14):. (PMID: 37508526)
Front Chem. 2023 Sep 06;11:1222047. (PMID: 37744065)
Chin J Nat Med. 2023 Nov;21(11):852-858. (PMID: 38035940)
Trends Cell Biol. 2023 Mar;33(3):189-203. (PMID: 35931610)
Comput Biol Med. 2022 Jun;145:105517. (PMID: 35585729)
Nano Res. 2022;15(7):6328-6339. (PMID: 35464625)
Bioorg Chem. 2024 Jul;148:107451. (PMID: 38759357)
Food Res Int. 2024 Aug;190:114653. (PMID: 38945587)
Int J Mol Sci. 2022 May 11;23(10):. (PMID: 35628179)
Eur J Med Chem. 2023 Jan 15;246:114943. (PMID: 36462438)
Cell Chem Biol. 2023 Nov 16;30(11):1366-1376.e7. (PMID: 37536341)
Int J Mol Sci. 2023 Jun 20;24(12):. (PMID: 37373516)
J Virol. 2023 Feb 28;97(2):e0192322. (PMID: 36779759)
Brief Bioinform. 2022 May 13;23(3):. (PMID: 35395683)
J Med Chem. 2021 Jun 10;64(11):7507-7532. (PMID: 34048243)
Molecules. 2023 Apr 03;28(7):. (PMID: 37049948)
Mol Pharm. 2018 Nov 5;15(11):4933-4946. (PMID: 30281314)
Viruses. 2022 May 02;14(5):. (PMID: 35632696)
Nat Commun. 2020 Oct 15;11(1):5204. (PMID: 33060576)
Grant Information:
25-LZIHPS-02 The research was supported by Science and Technology Innovation Project of CAAS.
Contributed Indexing:
Keywords: STING ligands; TLR7 ligands; dual-targeting drugs; molecular dynamics simulation; virtual screening
Substance Nomenclature:
0 (Ligands)
0 (Toll-Like Receptor 7)
0 (Membrane Proteins)
0 (Toll-Like Receptor 7)
0 (Membrane Proteins)
Entry Date(s):
Date Created: 20260110 Date Completed: 20260110 Latest Revision: 20260113
Update Code:
20260130
PubMed Central ID:
PMC12785509
DOI:
10.3390/ijms27010338
PMID:
41516215
Database:
MEDLINE
*Further Information*
*Toll-like receptor 7 (TLR7) and Stimulator of Interferon Genes (STING) ligands possess a series of immunomodulatory effects such as anti-infection, anti-tumor, and autoimmune-disease-alleviating effects. In this study, porcine TLR7 (pTLR7) and porcine STING (pSTING) were selected as targets, and molecular docking and virtual screening methods were used for screening of dual-target livestock immunomodulators. Finally, two compounds were screened with molecular docking scores higher than the positive control compounds. They have good binding ability with pTLR7 and pSTING proteins, as well as satisfactory predictive safety and pharmacokinetic properties. Molecular dynamics (MD) simulation results also indicated that the above ligands can form stable complexes with two target proteins. The average binding free energies of compound 2 with pTLR7 and pSTING were -28.65 kcal/mol and -30.12 kcal/mol, respectively, and of compound 7 with pTLR7 and pSTING were -35.93 kcal/mol and -31.70 kcal/mol, respectively, which were comparable to that of positive control ligands. The similarity of target proteins between pigs, humans, and mice, as well as the interactions between ligands and TLR7 and STING in different species, were analyzed. And analysis of predicted structure-activity relationship (SAR) was conducted. Briefly, compound 2 and compound 7 were predicted to form stable complexes with pTLR7 and pSTING, with satisfactory predicted physicochemical properties and pharmacokinetic characteristics, and represented candidates for experimental validation. This study supplies a research basis for the development, design, and structural modification of immune enhancers for animals.*