SpringerLink
Log in

A comprehensive molecular docking-based study to identify potential drug-candidates against the novel and emerging severe fever with thrombocytopenia syndrome virus (SFTSV) by targeting the nucleoprotein

  • Original Article
  • Published:
The Nucleus Aims and scope Submit manuscript

Abstract

Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerging haemorrhagic fever that is caused by an RNA virus called Severe fever with Thrombocytopenia Syndrome virus (SFTSV). The disease has spread globally with a case fatality rate of 30%. The nucleoprotein (N) of the virus has a pivotal role in replication and transcription of RNA inside the host. Considering that no specific treatment regime is suggested for the disease, N protein may be regarded as the potential candidate drug target. In the present study, in silico molecular docking was performed with 130 compounds (60 natural compounds and 70 repurposed synthetic drugs) against the N protein. Based on the binding affinity (kcal mol−1), we selected Cryptoleurine (− 10.323 kcal mol−1) and Ivermectin (− 10.327 kcal mol−1) as the top-ranked ligands from the natural compounds and repurposed synthetic drugs groups respectively, and pharmacophore analysis of these compounds along with other high performing ligands revealed that two aromatic and one acceptor groups could strongly interact with the target protein. Finally, molecular dynamic simulations of Cryptoleurine and Ivermectin showed stable interactions with the N protein of SFTSV. To conclude, Cryptoleurine and Ivermectin can be considered as a potential therapeutic agent against the infectious SFTS virus.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Data Availability Statement

Data shall be available on the valid request.

References

  1. Alotaibi BS, Ijaz M, Buabeid M, Kharaba ZJ, Yaseen HS, Murtaza G. Therapeutic effects and safe uses of plant-derived polyphenolic compounds in cardiovascular diseases: a review. Drug Des Devel Ther. 2021;15:4713–32. https://doi.org/10.2147/DDDT.S327238.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Arberas H, Guardo AC, Bargalló ME, Maleno MJ, Calvo M, Blanco JL, et al. In vitro effects of the CCR5 inhibitor maraviroc on human T cell function. J Antimicrob Chemother. 2013;68(3):577–86. https://doi.org/10.1093/jac/dks432.

    Article  CAS  PubMed  Google Scholar 

  3. Andersen SM, Rosada C, Dagnaes-Hansen F, Laugesen IG, de Darkó E, Dam TN, et al. Topical application of valrubicin has a beneficial effect on develo** skin tumors. Carcinogenesis. 2010;31(8):1483–90. https://doi.org/10.1093/carcin/bgq122.

    Article  CAS  PubMed  Google Scholar 

  4. Baker NA, Sept D, Joseph S, Holst MJ, McCammon JA. Electrostatics of nanosystems: application to microtubules and the ribosome. Proc Natl Acad Sci. 2001;98(18):10037–41. https://doi.org/10.1073/pnas.181342398.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Balduini CL, Noris P, Belletti S, Spedini P, Gamba G. In vitro and in vivo effects of desmopressin on platelet function. Haematologica. 1999;84(10):891–6.

    CAS  PubMed  Google Scholar 

  6. Bang M-S, Kim C-M, Kim D-M, Yun NR. Effective drugs against severe fever with thrombocytopenia syndrome virus in an in vitro model. Front Med. 2022. https://doi.org/10.3389/fmed.2022.839215.

    Article  Google Scholar 

  7. Barrows NJ, Campos RK, Powell ST, Prasanth KR, Schott-Lerner G, Soto-Acosta R, et al. A screen of FDA-approved drugs for inhibitors of Zika virus infection. Cell Host Microbe. 2016;20(2):259–70. https://doi.org/10.1016/j.chom.2016.07.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Boustie J, Stigliani J-L, Montanha J, Amoros M, Payard M, Girre L. Antipoliovirus structure−activity relationships of some aporphine alkaloids. J Nat Prod. 1998;61(4):480–4. https://doi.org/10.1021/np970382v.

    Article  CAS  PubMed  Google Scholar 

  9. Bussi G, Donadio D, Parrinello M. Canonical sampling through velocity rescaling. J Chem Phys. 2007;126(1): 014101. https://doi.org/10.1063/1.2408420.

    Article  CAS  PubMed  Google Scholar 

  10. Casel MA, Park SJ, Choi YK. Severe fever with thrombocytopenia syndrome virus: emerging novel phlebovirus and their control strategy. Exp Mol Med. 2021;53(5):713–22. https://doi.org/10.1038/s12276-021-00610-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chatterjee S, Kim C-M, Kim D-M. Potential efficacy of existing drug molecules against severe fever with thrombocytopenia syndrome virus: an in silico study. Sci Rep. 2021;11(1):20857. https://doi.org/10.1038/s41598-021-00294-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Chen T-H, Tsai M-J, Chang C-S, Xu L, Fu Y-S, Weng C-F. The exploration of phytocompounds theoretically combats SARS-CoV-2 pandemic against virus entry, viral replication and immune evasion. J Infect Public Health. 2023;16(1):42–54. https://doi.org/10.1016/j.jiph.2022.11.022.

    Article  PubMed  Google Scholar 

  13. Constantinides PP, Wasan KM. Lipid formulation strategies for enhancing intestinal transport and absorption of P-glycoprotein (P-gp) substrate drugs: In vitro/In vivo case studies. J Pharm Sci. 2007;96(2):235–48. https://doi.org/10.1002/jps.20780.

    Article  CAS  PubMed  Google Scholar 

  14. Cui F, Cao H-X, Wang L, Zhang S-F, Ding S-J, Yu X-J, et al. Clinical and epidemiological study on severe fever with thrombocytopenia syndrome in Yiyuan County, Shandong Province, China. Am J Trop Med Hyg. 2013;88(3):510–2. https://doi.org/10.4269/ajtmh.11-0760.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017;7(1):42717. https://doi.org/10.1038/srep42717.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Mokbel KE-DM, Baiuomy IR, Sabry AE-HA, Mohammed MM, El-Dardiry MA. In vivo assessment of the antischistosomal activity of curcumin loaded nanoparticles versus praziquantel in the treatment of Schistosoma mansoni. Sci Rep. 2020;10(1):15742. https://doi.org/10.1038/s41598-020-72901-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Elkaeed EB, Metwaly AM, Alesawy MS, Saleh AM, Alsfouk AA, Eissa IH. Discovery of potential SARS-CoV-2 papain-like protease natural inhibitors employing a multi-phase in silico approach. Life (Basel). 2022;12(9):1407. https://doi.org/10.3390/life12091407.

    Article  CAS  PubMed  Google Scholar 

  18. Ertl P, Rohde B, Selzer P. Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties. J Med Chem. 2000;43(20):3714–7. https://doi.org/10.1021/jm000942e.

    Article  CAS  PubMed  Google Scholar 

  19. Fadlalla M, Ahmed M, Ali M, Elshiekh AA, Yousef BA. Molecular docking as a potential approach in repurposing drugs against COVID-19: a systematic review and novel pharmacophore models. Curr Pharmacol Rep. 2022;8(3):212–26. https://doi.org/10.1007/s40495-022-00285-w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Gai Z, Liang M, Zhang Y, Zhang S, ** C, Wang S-W, et al. Person-to-person transmission of severe fever with thrombocytopenia syndrome bunyavirus through blood contact. Clin Infect Dis. 2012;54(2):249–52. https://doi.org/10.1093/cid/cir776.

    Article  PubMed  Google Scholar 

  21. Gills JJ, Lopiccolo J, Tsurutani J, Shoemaker RH, Best CJM, Abu-Asab MS, et al. Nelfinavir, a lead HIV protease inhibitor, is a broad-spectrum, anticancer agent that induces endoplasmic reticulum stress, autophagy, and apoptosis in vitro and in vivo. Clin Cancer Res. 2007;13(17):5183–94. https://doi.org/10.1158/1078-0432.CCR-07-0161.

    Article  CAS  PubMed  Google Scholar 

  22. Giordano D, Biancaniello C, Argenio MA, Facchiano A. Drug design by pharmacophore and virtual screening approach. Pharmaceuticals (Basel). 2022;15(5):646. https://doi.org/10.3390/ph15050646.

    Article  CAS  PubMed  Google Scholar 

  23. Gong Z, Gu S, Zhang Y, Sun J, Wu X, Ling F, et al. Probable aerosol transmission of severe fever with thrombocytopenia syndrome virus in southeastern China. Clin Microbiol Infect. 2015;21(12):1115–20. https://doi.org/10.1016/j.cmi.2015.07.024.

    Article  CAS  PubMed  Google Scholar 

  24. Gour A, Manhas D, Bag S, Gorain B, Nandi U. Flavonoids as potential phytotherapeutics to combat cytokine storm in SARS-CoV-2. Phytother Res. 2021;35(8):4258–83. https://doi.org/10.1002/ptr.7092.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Halgren TA. Merck molecular force field. II. MMFF94 van der Waals and electrostatic parameters for intermolecular interactions. J Comput Chem. 1996;17:520–52.

    Article  CAS  Google Scholar 

  26. Hassanizadeh S, Shojaei M, Bagherniya M, Orekhov AN, Sahebkar A. Effect of nano-curcumin on various diseases: a comprehensive review of clinical trials. BioFactors. 2023;49(3):512–33. https://doi.org/10.1002/biof.1932.

    Article  CAS  PubMed  Google Scholar 

  27. Hay A-E, Hélesbeux J-J, Duval O, Labaïed M, Grellier P, Richomme P. Antimalarial xanthones from Calophyllum caledonicum and Garcinia vieillardii. Life Sci. 2004;75(25):3077–85. https://doi.org/10.1016/j.lfs.2004.07.009.

    Article  CAS  PubMed  Google Scholar 

  28. Hollingsworth SA, Dror RO. Molecular dynamics simulation for all. Neuron. 2018;99(6):1129–43. https://doi.org/10.1016/j.neuron.2018.08.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hou T, Wang J. Structure – ADME relationship: still a long way to go? Expert Opin Drug Metab Toxicol. 2008;4(6):759–70. https://doi.org/10.1517/17425255.4.6.759.

    Article  CAS  PubMed  Google Scholar 

  30. Huang X-Y, Du Y-H, Wang H-F, You A-G, Li Y, Su J, et al. Prevalence of severe fever with thrombocytopenia syndrome virus in animals in Henan Province, China. Infect Dis Poverty. 2019;8(1):56. https://doi.org/10.1186/s40249-019-0569-x.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Huang Y, Chen W, Wallace JA, Shen J. All-Atom Continuous constant pH Molecular dynamics with particle Mesh Ewald and titratable water. J Chem Theory Comput. 2016;12(11):5411–21. https://doi.org/10.1021/acs.jctc.6b00552.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hu X-J, ** H-Z, Xu W-Z, Chen M, Liu X-H, Zhang W, et al. Anti-inflammatory and analgesic activities of Edgeworthia chrysantha and its effective chemical constituents. Biol Pharm Bull. 2008;31(9):1761–5. https://doi.org/10.1248/bpb.31.1761.

    Article  CAS  PubMed  Google Scholar 

  33. Idris MO, Yekeen AA, Alakanse OS, Durojaye OA. Computer-aided screening for potential TMPRSS2 inhibitors: a combination of pharmacophore modeling, molecular docking and molecular dynamics simulation approaches. J Biomol Struct Dyn. 2021;39(15):5638–56. https://doi.org/10.1080/07391102.2020.1792346.

    Article  CAS  PubMed  Google Scholar 

  34. Jiang XL, Zhang S, Jiang M, Bi ZQ, Liang MF, Ding SJ, et al. A cluster of person-to-person transmission cases caused by Sfts virus in Penglai, China. Clin Microbiol Infect. 2015;21(3):274–9. https://doi.org/10.1016/j.cmi.2014.10.006.

    Article  CAS  PubMed  Google Scholar 

  35. ** Lee M, Kim K-H, Yi J, Choi SJ, Choe PG, Park WB, et al. In vitro antiviral activity of Ribavirin against severe fever with thrombocytopenia syndrome virus. Korean J Intern Med. 2017;32(4):731–7. https://doi.org/10.3904/kjim.2016.109.

    Article  CAS  Google Scholar 

  36. Jourdan J-P, Bureau R, Rochais C, Dallemagne P. Drug repositioning: a brief overview. J Pharm Pharmacol. 2020;72(9):1145–51. https://doi.org/10.1111/jphp.13273.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Karplus M, McCammon JA. Molecular dynamics simulations of biomolecules. Nat Struct Mol Biol. 2002;9(9):646–52. https://doi.org/10.1038/nsb0902-646.

    Article  CAS  Google Scholar 

  38. Khan KM, Patel JB, Schaefer TJ. Nifedipine. StatPearls.2022. http://www.ncbi.nlm.nih.gov/books/NBK537052/

  39. Kim K-H, Yi J, Kim G, Choi SJ, Jun KI, Kim N-H, et al. Severe fever with thrombocytopenia syndrome, South Korea, 2012. Emerg Infect Dis. 2013;19(11):1892–4. https://doi.org/10.3201/eid1911.130792.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Kim WY, Choi W, Park S-W, Wang EB, Lee W-J, Jee Y, et al. Nosocomial transmission of severe fever with thrombocytopenia syndrome in Korea. Clin Infect Dis. 2015;60(11):1681–3. https://doi.org/10.1093/cid/civ128.

    Article  CAS  PubMed  Google Scholar 

  41. Koes DR, Camacho CJ. ZINCPharmer: pharmacophore search of the ZINC database. Nucleic Acids Res. 2012;40(Web Server issue):W409–14. https://doi.org/10.1093/nar/gks378.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Koes DR, Pabon NA, Deng X, Phillips MA, Camacho CJ. A Teach-discover-treat application of ZincPharmer: an online interactive pharmacophore modeling and virtual screening tool. PLoS ONE. 2015;10(8):e0134697. https://doi.org/10.1371/journal.pone.0134697.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Kohl C, Brinkmann A, Radonić A, Dabrowski PW, Nitsche A, Mühldorfer K, et al. Zwiesel bat banyangvirus, a potentially zoonotic Huaiyangshan banyangvirus (formerly known as SFTS)–like banyangvirus in Northern bats from Germany. Sci Rep. 2020;10(1):1370. https://doi.org/10.1038/s41598-020-58466-w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Krishnamurthy N, Grimshaw AA, Axson SA, Choe SH, Miller JE. Drug repurposing: a systematic review on root causes, barriers and facilitators. BMC Health Serv Res. 2022;22(1):970. https://doi.org/10.1186/s12913-022-08272-z.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Kumar S, Chowdhury S, Kumar S. In silico repurposing of antipsychotic drugs for Alzheimer’s disease. BMC Neurosci. 2017;18(1):76. https://doi.org/10.1186/s12868-017-0394-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kumari R, Kumar R. Open source drug discovery consortium, Lynn A. g_mmpbsa–a GROMACS tool for high-throughput MM-PBSA calculations. J Chem Inf Model. 2014;54(7):1951–62. https://doi.org/10.1021/ci500020m.

    Article  CAS  PubMed  Google Scholar 

  47. Lei X-Y, Liu M-M, Yu X-J. Severe fever with thrombocytopenia syndrome and its pathogen SFTSV. Virol. 2020;94(6):e01575-e1619. https://doi.org/10.1016/j.micinf.2014.12.002.

    Article  Google Scholar 

  48. Li D. A highly pathogenic new bunyavirus emerged in China. Emerg Microbes Infect. 2013;2(1):1–4. https://doi.org/10.1038/emi.2013.1.

    Article  CAS  Google Scholar 

  49. Li H, Zhang L-K, Li S-F, Zhang S-F, Wan W-W, Zhang Y-L, et al. Calcium channel blockers reduce severe fever with thrombocytopenia syndrome virus (SFTSV) related fatality. Cell Res. 2019;29(9):739–53. https://doi.org/10.1038/s41422-019-0214-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Lin T-L, Ou S-C, Maeda K, Shimoda H, Chan JP-W, Tu W-C, et al. The first discovery of severe fever with thrombocytopenia syndrome virus in Taiwan. Emerg Microbes Infect. 2020;9(1):148–51. https://doi.org/10.1080/22221751.2019.1710436.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Liu Q, He B, Huang S-Y, Wei F, Zhu X-Q. Severe fever with thrombocytopenia syndrome, an emerging tick-borne zoonosis. Lancet Infect Dis. 2014;14(8):763–72. https://doi.org/10.1016/S1473-3099(14)70718-2.

    Article  CAS  PubMed  Google Scholar 

  52. Markowitz M, Conant M, Hurley A, Schluger R, Duran M, Peterkin J, et al. A preliminary evaluation of nelfinavir mesylate, an inhibitor of human immunodeficiency virus (HIV)-1 protease, to treat HIV infection. J Infect Dis. 1998;177(6):1533–40. https://doi.org/10.1086/515312.

    Article  CAS  PubMed  Google Scholar 

  53. Martinez L. Automatic identification of mobile and rigid substructures in molecular dynamics simulations and fractional structural fluctuation analysis. PLoS ONE. 2015;10(3): e0119264. https://doi.org/10.1371/journal.pone.0119264.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Montes-Grajales D, Puerta-Guardo H, Espinosa DA, Harris E, Caicedo-Torres W, Olivero-Verbel J, et al. In silico drug repurposing for the identification of potential candidate molecules against arboviruses infection. Antiviral Res. 2020;173: 104668. https://doi.org/10.1016/j.antiviral.2019.104668.

    Article  CAS  PubMed  Google Scholar 

  55. Nag A, Banerjee R, Chowdhury RR, Krishnapura VC. Phytochemicals as potential drug candidates for targeting SARS CoV 2 proteins, an in silico study. VirusDis. 2021;32(1):98–107. https://doi.org/10.1007/s13337-021-00654-x.

    Article  CAS  Google Scholar 

  56. Nag A, Banerjee R, Paul S, Kundu R. Curcumin inhibits spike protein of new SARS-CoV-2 variant of concern (VOC) Omicron, an in silico study. Comput Biol Med. 2022;146: 105552. https://doi.org/10.1016/j.compbiomed.2022.105552.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Nag A, Paul S, Banerjee R, Kundu R. In silico study of some selective phytochemicals against a hypothetical SARS-CoV-2 spike RBD using molecular docking tools. Comput Biol Med. 2021;137: 104818. https://doi.org/10.1016/j.compbiomed.2021.104818.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Odot J. In vitro and in vivo anti-tumoral effect of curcumin against melanoma cells. Int J Cancer. 2004;111(3):381–7. https://doi.org/10.1002/ijc.20160.

    Article  CAS  PubMed  Google Scholar 

  59. Oferkin IV, Katkova EV, Sulimov AV, Kutov DC, Sobolev SI, Voevodin VV, et al. Evaluation of docking target functions by the comprehensive investigation of protein-ligand energy minima. Adv Bioinformatics. 2015;2015: 126858. https://doi.org/10.1155/2015/126858.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Opo FADM, Rahman MM, Ahammad F, Ahmed I, Bhuiyan MA, Asiri AM. Structure based pharmacophore modeling, virtual screening, molecular docking and ADMET approaches for identification of natural anti-cancer agents targeting XIAP protein. Sci Rep. 2021;11(1):4049. https://doi.org/10.1038/s41598-021-83626-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Parrinello M, Rahman A. Crystal structure and pair potentials: a molecular-dynamics study. Phys Rev Lett. 1980;45(14):1196–9. https://doi.org/10.1103/PhysRevLett.45.1196.

    Article  CAS  Google Scholar 

  62. Piplani S. Computationally repurposed drugs and natural products against RNA dependent RNA polymerase as potential COVID-19. Mol Biomed. 2021;2(28):12. https://doi.org/10.1186/s43556-021-00050-3.

    Article  Google Scholar 

  63. Vivek-Ananth RP, Kumar Sahoo A, Srivastava A, Samal A. Virtual screening of phytochemicals from Indian medicinal plants against the endonuclease domain of SFTS virus L polymerase. RSC Adv. 2022;12(10):6234–47. https://doi.org/10.1039/D1RA06702H.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Rababi D, Nag A. Evaluation of therapeutic potentials of selected phytochemicals against Nipah virus, a multi-dimensional in silico study. 3 Biotech. 2023;13(6):174. https://doi.org/10.1007/s13205-023-03595-y.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Randhawa V, Pathania S, Kumar M. Computational identification of potential multitarget inhibitors of Nipah virus by molecular docking and molecular dynamics. Microorganisms. 2022;10(6):1181. https://doi.org/10.3390/microorganisms10061181.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Ripoll GV, Giron S, Krzymuski MJ, Hermo GA, Gomez DE, Alonso DF. Antitumor effects of desmopressin in combination with chemotherapeutic agents in a mouse model of breast cancer. Anticancer Res. 2008;28(5A):2607–11.

    CAS  PubMed  Google Scholar 

  67. Sahi N, Nguyen R, Santos C. Loperamide - StatPearls - NCBI Bookshelf. 2022 [cited 2023 Feb 25]. https://www.ncbi.nlm.nih.gov/books/NBK557885/

  68. Seo J-W, Kim D, Yun N, Kim D-M. Clinical update of severe fever with thrombocytopenia syndrome. Viruses. 2021;13(7):1213. https://doi.org/10.3390/v13071213.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Sharmeen S, Skrtic M, Sukhai MA, Hurren R, Gronda M, Wang X, et al. The antiparasitic agent ivermectin induces chloride-dependent membrane hyperpolarization and cell death in leukemia cells. Blood. 2010;116(18):3593–603. https://doi.org/10.1182/blood-2010-01-262675.

    Article  CAS  PubMed  Google Scholar 

  70. Shen S, Duan X, Wang B, Zhu L, Zhang Y, Zhang J, et al. A novel tick-borne phlebovirus, closely related to severe fever with thrombocytopenia syndrome virus and Heartland virus, is a potential pathogen. Emerg Microbes Infect. 2018;7(1):95. https://doi.org/10.1038/s41426-018-0093-2.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Shimojima M, Fukushi S, Tani H, Yoshikawa T, Fukuma A, Taniguchi S, et al. Effects of Ribavirin on severe fever with thrombocytopenia syndrome virus in vitro. Jpn J Infect Dis. 2014;67(6):423–7. https://doi.org/10.7883/yoken.67.423.

    Article  CAS  PubMed  Google Scholar 

  72. Singh J, Kumar M, Mansuri R, Sahoo GC, Deep A. Inhibitor designing, virtual screening, and docking studies for methyltransferase: a potential target against dengue virus. J Pharm Bioallied Sci. 2016;8(3):188–94. https://doi.org/10.4103/0975-7406.171682.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Song TY, Yang EM, Kim CJ. A pediatric case of severe fever with thrombocytopenia syndrome in Korea. Emerg Infect Dis. 2013;19(11):1892–4. https://doi.org/10.3346/jkms.2017.32.4.704.

    Article  Google Scholar 

  74. Suksamrarn S, Suwannapoch N, Phakhodee W, Thanuhiranlert J, Ratananukul P, Chimnoi N, et al. Antimycobacterial activity of prenylated xanthones from the fruits of Garcinia mangostana. Chem Pharm Bull (Tokyo). 2003;51(7):857–9. https://doi.org/10.1248/cpb.51.857.

    Article  CAS  PubMed  Google Scholar 

  75. Takahashi T, Maeda K, Suzuki T, Ishido A, Shigeoka T, Tominaga T, et al. The first identification and retrospective study of severe fever with thrombocytopenia syndrome in Japan. J Infect Dis. 2014;209(6):816–27. https://doi.org/10.1093/infdis/jit603.

    Article  CAS  PubMed  Google Scholar 

  76. Takayama-Ito M, Saijo M. Antiviral drugs against severe fever with thrombocytopenia syndrome virus infection. Front Microbiol. 2020;11:150. https://doi.org/10.3389/fmicb.2020.00150.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Tran XC, Yun Y, Van An L, Kim S-H, Thao NTP, Man PKC, et al. Endemic severe fever with thrombocytopenia syndrome. Vietnam Emerg Infect Dis. 2019;25(5):1029–31. https://doi.org/10.3201/eid2505.181463.

    Article  PubMed  Google Scholar 

  78. Trivedi J, Mohan M, Byrareddy SN. Drug repurposing approaches to combating viral infections. J Clin Med. 2020;9(11):3777. https://doi.org/10.3390/jcm9113777.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Umesh HR, Ramesh KV, Devaraju KS. Molecular docking studies of phytochemicals against trehalose–6–phosphate phosphatases of pathogenic microbes. Beni-Suef Univ J Basic Appl Sci. 2020. https://doi.org/10.1186/s43088-019-0028-6.

    Article  Google Scholar 

  80. Urata S, Yasuda J, Iwasaki M. Loperamide inhibits replication of severe fever with thrombocytopenia syndrome virus. Viruses. 2021;13(5):869. https://doi.org/10.3390/v13050869.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Van Aalten DMF, Bywater R, Findlay JBC, Hendlich M, Hooft RWW, Vriend G. PRODRG, a program for generating molecular topologies and unique molecular descriptors from coordinates of small molecules. J Comput Aided Mol Des. 1996;10(3):255–62. https://doi.org/10.1007/BF00355047.

    Article  PubMed  Google Scholar 

  82. Varghese FS, Kaukinen P, Gläsker S, Bespalov M, Hanski L, Wennerberg K, et al. Discovery of berberine, abamectin and ivermectin as antivirals against chikungunya and other alphaviruses. Antiviral Res. 2016;126:117–24. https://doi.org/10.1016/j.antiviral.2015.12.012.

    Article  CAS  PubMed  Google Scholar 

  83. Wagstaff KM, Sivakumaran H, Heaton SM, Harrich D, Jans DA. Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. Biochem J. 2012;443(3):851–6. https://doi.org/10.1042/BJ20120150.

    Article  CAS  PubMed  Google Scholar 

  84. Wang C, Greene D, **ao L, Qi R, Luo R. Recent developments and applications of the MMPBSA method. Front Mol Biosci. 2018;10(4):87. https://doi.org/10.3389/fmolb.2017.00087.

    Article  CAS  Google Scholar 

  85. Wang E, Sun H, Wang J, Wang Z, Liu H, Zhang JZH, et al. End-point binding free energy calculation with MM/PBSA and MM/GBSA: strategies and applications in drug design. Chem Rev. 2019;119(16):9478–508. https://doi.org/10.1021/acs.chemrev.9b00055.

    Article  CAS  PubMed  Google Scholar 

  86. Wang W, Li W, Wen Z, Wang C, Liu W, Zhang Y, et al. Gossypol broadly inhibits coronaviruses by targeting RNA-dependent RNA polymerases. Adv Sci (Weinh). 2022;9(35): e2203499. https://doi.org/10.1002/advs.202203499.

    Article  CAS  PubMed  Google Scholar 

  87. Yan S, Ci X, Chen N, Chen C, Li X, Chu X, et al. Anti-inflammatory effects of ivermectin in mouse model of allergic asthma. Inflamm Res. 2011;60(6):589–96. https://doi.org/10.1007/s00011-011-0307-8.

    Article  CAS  PubMed  Google Scholar 

  88. Yao K, Nagashima K, Miki H. Pharmacological, pharmacokinetic, and clinical properties of benidipine hydrochloride, a novel, long-acting calcium channel blocker. J Pharmacol Sci. 2006;100(4):243–61. https://doi.org/10.1254/jphs.dtj05001x.

    Article  CAS  PubMed  Google Scholar 

  89. Yousefi H, Mashouri L, Okpechi SC, Alahari N, Alahari SK. Repurposing existing drugs for the treatment of COVID-19/SARS-CoV-2 infection: a review describing drug mechanisms of action. Biochem Pharmacol. 2021;183: 114296. https://doi.org/10.1016/j.bcp.2020.114296.

    Article  CAS  PubMed  Google Scholar 

  90. Yu X-J, Liang M-F, Zhang S-Y, Liu Y, Li J-D, Sun Y-L, et al. Fever with thrombocytopenia associated with a novel Bunyavirus in China. N Engl J Med. 2011;364(16):1523–32. https://doi.org/10.1056/NEJMoa1010095.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Yuan Y, Lu Q-B, Yao W-S, Zhao J, Zhang X-A, Cui N, et al. Clinical efficacy and safety evaluation of favipiravir in treating patients with severe fever with thrombocytopenia syndrome. EBioMedicine. 2021. https://doi.org/10.1016/j.ebiom.2021.103591.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Zhang Y, Chen W. Biochanin a inhibits lipopolysaccharide-induced inflammatory cytokines and mediators production in BV2 microglia. Neurochem Res. 2015;40(1):165–71. https://doi.org/10.1007/s11064-014-1480-2.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

NA.

Author information

Author notes

  1. Sutirtha Sengupta and Sweta Mohanty have contributed equally to this work.

Authors and Affiliations

  1. Department of Life Sciences, CHRIST (Deemed to Be University), Bangalore, Karnataka, India

    Sutirtha Sengupta, Sweta Mohanty, Deblina Rababi & Anish Nag

Authors
  1. Sutirtha Sengupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sweta Mohanty
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Deblina Rababi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anish Nag
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SS and SM performed the work, DR drafted the manuscript, AN conceptualized, supervised the work and finalized the manuscript.

Corresponding author

Correspondence to Anish Nag.

Ethics declarations

Conflict of interest

Authors declare there is no conflict of interest.

Ethical approval

NA.

Informed consent

All authors have read the manuscript and consented to publish.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Corresponding Editor: Rita Kundu; Reviewers: Vidya Niranjan, Preethi Kathirvel.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 37 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sengupta, S., Mohanty, S., Rababi, D. et al. A comprehensive molecular docking-based study to identify potential drug-candidates against the novel and emerging severe fever with thrombocytopenia syndrome virus (SFTSV) by targeting the nucleoprotein. Nucleus (2024). https://doi.org/10.1007/s13237-024-00495-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s13237-024-00495-1

Keywords

Search

Navigation