Interaction of Mosquito’s hppd Enzyme with Lansoprazole Sulfide A New Hope to Tackle the Mosquito Menace – an in-Silico Study

Year : 2026 | Volume : 03 | Issue : 01 | Page : 1 11
    By

    Prakash Vaithyanathan,

  1. Science teacher, Department if research and educational lab, D3 Drug Tech Lab Pvt ltd.Majithbstreet, Dharampuri, Tamil Nadu., India

Abstract

Tyrosine detoxification is an important physiological process that helps blood-feeding insects, such as mosquitoes that transmit Plasmodium parasites causing malaria, digest their blood meals. An enzyme known as 4-hydroxyphenylpyruvate dioxygenase (HPPD), which is part of the tyrosine detoxification pathway, helps in removing excess tyrosine in a high-protein blood meal. Excess tyrosine can be lethal to the insects, and hence, the role of HPPD enzyme is very critical. Inhibitors of HPPD enzyme have been used as herbicides, and it has been suggested that they can also be used to control the mosquito menace. For the first time, docking studies and molecular dynamics simulations have demonstrated that Lansoprazole sulfone or Lansoprazole sulfide, metabolites of Lansoprazole, can modulate the activity of the HPPD enzyme, which can be lethal to mosquitoes through its interaction with critical residues. In addition, a comparison with the HPPD modulating activity of theobromine’s metabolite, 7-methyl xanthine, is also presented.

Keywords: Keywords: 7-methyl xanthine, enzyme, HPPD, Lansoprazole sulfide, Lansoprazole sulfone, mosquitoes, tyrosine detoxification

[This article belongs to International Journal of Insects ]

How to cite this article:
Prakash Vaithyanathan. Interaction of Mosquito’s hppd Enzyme with Lansoprazole Sulfide A New Hope to Tackle the Mosquito Menace – an in-Silico Study. International Journal of Insects. 2026; 03(01):1-11.
How to cite this URL:
Prakash Vaithyanathan. Interaction of Mosquito’s hppd Enzyme with Lansoprazole Sulfide A New Hope to Tackle the Mosquito Menace – an in-Silico Study. International Journal of Insects. 2026; 03(01):1-11. Available from: https://journals.stmjournals.com/iji/article=2026/view=236313


References

  1. 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):259-270. doi: 10.1016/j.chom.2016.07.004.
  2. Onen H, Luzala MM, Kigozi S, Sikumbili RM, Muanga C-JK, Zola EN, et al. Mosquito-borne diseases and their control strategies: an overview focused on green synthesized plant-based metallic nanoparticles. Insects. 2023;14(3):221. doi: 10.3390/insects14030221.
  3. Paton DG, Childs LM, Itoe MA, et al. Exposing Anopheles mosquitoes to antimalarials blocks Plasmodium parasite transmission. Nature. 2019;567:239-243. doi: 10.1038/s41586-019-0973-1.
  4. Sparks TC, Nauen R. IRAC: mode of action classification and insecticide resistance management. Pestic Biochem Physiol. 2015;121:122-128. doi: 10.1016/j.pestbp.2014.11.014.
  5. Knutsson S, Kindahl T, Engdahl C, Nikjoo D, Forsgren N, Kitur S, et al. N-Aryl-N’-ethyleneaminothioureas effectively inhibit acetylcholinesterase 1 from disease-transmitting mosquitoes. Eur J Med Chem. 2017;134:415-427. doi: 10.1016/j.ejmech.2017.03.050.
  6. Wawer M, Peltason L, Weskamp N, Teckentrup A, Bajorath J. Structure–activity relationship anatomy by network-like similarity graphs and local structure–activity relationship indices. J Med Chem. 2008;51(19):6075-6084.
  7. Soderlund DM. Molecular mechanisms of pyrethroid insecticide neurotoxicity: recent advances. Arch Toxicol. 2012;86:165–181. doi: 10.1007/s00204-011-0726-x.
  8. Dong K, Du Y, Rinkevich F, Nomura Y, Xu P, Wang L, et al. Molecular biology of insect sodium channels and pyrethroid resistance. Insect Biochem Mol Biol. 2014;50:1-17. doi: 10.1016/j.ibmb.2014.03.012.
  9. Peterson BF. Microbiome toxicology — bacterial activation and detoxification of insecticidal compounds. Curr Opin Insect Sci. 2024;63:101192. doi: 10.1016/j.cois.2024.101192.
  10. Benelli G, Jeffries CL, Walker T. Biological control of mosquito vectors: past, present, and future. Insects. 2016;7(4):52. doi:10.3390/insects7040052.
  11. Balczun C, Siemanowski J, Pausch JK, Helling S, Marcus K, Stephan C, et al. Intestinal aspartate proteases TiCatD and TiCatD2 of the haematophagous bug Triatoma infestans: sequence characterisation, expression pattern and characterisation of proteolytic activity. Insect Biochem Mol Biol. 2012;42(4):240-250. doi: 10.1016/j.ibmb.2011.12.006.
  12. Ribeiro JMC, Genta FA, Sorgine MHF, Logullo R, Mesquita RD, et al. An insight into the transcriptome of the digestive tract of the bloodsucking bug Rhodnius prolixus. PLoS Negl Trop Dis. 2014;8(1):e2594.
  13. Haines LR, Trett A, Rose C, García N, Sterkel M, McGuinness D, et al. Anopheles mosquito survival and pharmacokinetic modeling show the mosquitocidal activity of nitisinone. Sci Transl Med. 2025;17(791).
  14. Dong J, Fu Y-X, Zheng B-F, Chen M-X, Chen Q, Wishwajith K, et al. Repurposing 4-hydroxyphenylpyruvate dioxygenase inhibitors as novel agents for mosquito control: a structure-based design approach. Int J Biol Macromol. 2025;315(2):144566.
  15. Irfan N, Vaithyanathan P, Anandaram H, Zaidh SM, Varshini SP, Ahamed HN. Active and allosteric site binding MM-QM studies of methylidene tetracyclo derivative in PCSK9 protein intended to make a safe antilipidemic agent. J Biomol Struct Dyn. 2024;42(13):6813–6822.
  16. Zaidh SM, Aher KB, Bhavar GB, Irfan N, Ahmed HN, Ismail Y. Genes adaptability and NOL6 protein inhibition studies of fabricated flavan-3-ols lead skeleton intended to treat breast carcinoma. Int J Biol Macromol. 2024;258:127661.
  17. Zaidh SM, Vengateswaran HT, Habeeb M, Aher KB, Bhavar GB, Irfan N, et al. Network pharmacology and AI in cancer research: uncovering biomarkers and therapeutic targets for RALGDS mutations. Sci Rep. 2025;15(1):1–13.
  18. Ahamed LHTA, Ismail Y, Irfan N, Zaidh SM, Sundaram TS. Investigating the toxicity of malachite green and copper sulfate in brine shrimp: in-vivo and computational study. Toxicol Rep. 2024;11.
  19. Irfan N, Vaithyanathan P, Anandaram H, Zaidh SM, Varshini SP, Ahmed HN, et al. Active and allosteric site binding molecular mechanics–quantum mechanics studies of stevioside derivative in PCSK9 protein intended to provide a safe antilipidemic agent. bioRxiv. 2023;2023.05.04.539221.
  20. Priya RM, Irfan N, Zaidh SM. Binding and dynamics of diferuloylmethane-pyrimidine with C-Met protein. J Indian Chem Soc. 2025;101849.
  21. Shareef THMA, Masood MMD, Navabshan I, Musthafa MS. Phytoconstituents profiling of indigenous herbal drugs and its in vitro microbial, in silico biological examination against SARS-CoV-2. World J Tradit Chin Med. 2024;10(1):121–136.

Regular Issue Subscription Review Article
Volume 03
Issue 01
Received 19/11/2025
Accepted 01/12/2025
Published 27/01/2026
Publication Time 69 Days


Login


My IP

PlumX Metrics