Schistosomiasis Drug Discovery in the Era of Automation and Artificial Intelligence

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2021 Jun 17

PMID 34135888

Citations 9

Authors

Jose T Moreira-Filho

Arthur C Silva

Rafael F Dantas

Barbara F Gomes

Lauro R Souza Neto

Jose Brandao-Neto

Raymond J Owens

Nicholas Furnham

Bruno J Neves

Floriano P Silva-Junior

Carolina H Andrade

Affiliations

Soon will be listed here.

Abstract

Schistosomiasis is a parasitic disease caused by trematode worms of the genus and affects over 200 million people worldwide. The control and treatment of this neglected tropical disease is based on a single drug, praziquantel, which raises concerns about the development of drug resistance. This, and the lack of efficacy of praziquantel against juvenile worms, highlights the urgency for new antischistosomal therapies. In this review we focus on innovative approaches to the identification of antischistosomal drug candidates, including the use of automated assays, fragment-based screening, computer-aided and artificial intelligence-based computational methods. We highlight the current developments that may contribute to optimizing research outputs and lead to more effective drugs for this highly prevalent disease, in a more cost-effective drug discovery endeavor.

Citing Articles

and Evaluation of the Antischistosomal Activity of Polygodial and 9-Deoxymuzigadial Isolated from Branches.

Umehara E, Cajas R, Conceicao G, Antar G, Andricopulo A, de Moraes J Molecules. 2025; 30(2).

PMID: 39860137 PMC: 11767830. DOI: 10.3390/molecules30020267.

Computer-aided discovery of novel SmDHODH inhibitors for schistosomiasis therapy: Ligand-based drug design, molecular docking, molecular dynamic simulations, drug-likeness, and ADMET studies.

Jaafaru S, Uzairu A, Hossain S, Ullah M, Sallau M, Ndukwe G PLoS Negl Trop Dis. 2024; 18(9):e0012453.

PMID: 39264908 PMC: 11392272. DOI: 10.1371/journal.pntd.0012453.

A comprehensive exploration of schistosomiasis: Global impact, molecular characterization, drug discovery, artificial intelligence and future prospects.

Ekloh W, Asafu-Adjaye A, Tawiah-Mensah C, Ayivi-Tosuh S, Quartey N, Aiduenu A Heliyon. 2024; 10(12):e33070.

PMID: 38988508 PMC: 11234110. DOI: 10.1016/j.heliyon.2024.e33070.

Unveiling potent inhibitors for schistosomiasis through ligand-based drug design, molecular docking, molecular dynamics simulations and pharmacokinetics predictions.

Jaafaru S, Uzairu A, Bayil I, Sallau M, Ndukwe G, Ibrahim M PLoS One. 2024; 19(6):e0302390.

PMID: 38923997 PMC: 11207139. DOI: 10.1371/journal.pone.0302390.

Therapeutic Potential of Natural Products in the Treatment of .

Azevedo C, Meira C, da Silva J, Moura D, de Oliveira S, da Costa C Molecules. 2023; 28(19).

PMID: 37836650 PMC: 10574020. DOI: 10.3390/molecules28196807.

References

Fallon P, Sturrock R, Niang A, Doenhoff M . Short report: diminished susceptibility to praziquantel in a Senegal isolate of Schistosoma mansoni. Am J Trop Med Hyg. 1995; 53(1):61-2. View

Mondal M, Radeva N, Fanlo-Virgos H, Otto S, Klebe G, Hirsch A . Fragment Linking and Optimization of Inhibitors of the Aspartic Protease Endothiapepsin: Fragment-Based Drug Design Facilitated by Dynamic Combinatorial Chemistry. Angew Chem Int Ed Engl. 2016; 55(32):9422-6. PMC: 5113778. DOI: 10.1002/anie.201603074. View

Buro C, Oliveira K, Lu Z, Leutner S, Beckmann S, Dissous C . Transcriptome analyses of inhibitor-treated schistosome females provide evidence for cooperating Src-kinase and TGFβ receptor pathways controlling mitosis and eggshell formation. PLoS Pathog. 2013; 9(6):e1003448. PMC: 3681755. DOI: 10.1371/journal.ppat.1003448. View

Sheng C, Zhang W . Fragment informatics and computational fragment-based drug design: an overview and update. Med Res Rev. 2012; 33(3):554-98. DOI: 10.1002/med.21255. View

Chan J, McCorvy J, Acharya S, Johns M, Day T, Roth B . A Miniaturized Screen of a Schistosoma mansoni Serotonergic G Protein-Coupled Receptor Identifies Novel Classes of Parasite-Selective Inhibitors. PLoS Pathog. 2016; 12(5):e1005651. PMC: 4871480. DOI: 10.1371/journal.ppat.1005651. View

Chawla K, Modena M, Ravaynia P, Lombardo F, Leonhardt M, Panic G . Impedance-Based Microfluidic Assay for Automated Antischistosomal Drug Screening. ACS Sens. 2018; 3(12):2613-2620. PMC: 6396876. DOI: 10.1021/acssensors.8b01027. View

Ciallella H, Zhu H . Advancing Computational Toxicology in the Big Data Era by Artificial Intelligence: Data-Driven and Mechanism-Driven Modeling for Chemical Toxicity. Chem Res Toxicol. 2019; 32(4):536-547. PMC: 6688471. DOI: 10.1021/acs.chemrestox.8b00393. View

Silvestri I, Lyu H, Fata F, Boumis G, Miele A, Ardini M . Fragment-Based Discovery of a Regulatory Site in Thioredoxin Glutathione Reductase Acting as "Doorstop" for NADPH Entry. ACS Chem Biol. 2018; 13(8):2190-2202. PMC: 6905387. DOI: 10.1021/acschembio.8b00349. View

Wang Y, Xiao J, Suzek T, Zhang J, Wang J, Zhou Z . PubChem's BioAssay Database. Nucleic Acids Res. 2011; 40(Database issue):D400-12. PMC: 3245056. DOI: 10.1093/nar/gkr1132. View

10.

McCusker P, Mian M, Li G, Olp M, Tiruveedhula V, Rashid F . Non-sedating benzodiazepines cause paralysis and tissue damage in the parasitic blood fluke Schistosoma mansoni. PLoS Negl Trop Dis. 2019; 13(11):e0007826. PMC: 6881066. DOI: 10.1371/journal.pntd.0007826. View

11.

Osborne J, Panova S, Rapti M, Urushima T, Jhoti H . Fragments: where are we now?. Biochem Soc Trans. 2020; 48(1):271-280. DOI: 10.1042/BST20190694. View

12.

Wangchuk P, Giacomin P, Pearson M, Smout M, Loukas A . Identification of lead chemotherapeutic agents from medicinal plants against blood flukes and whipworms. Sci Rep. 2016; 6:32101. PMC: 5004179. DOI: 10.1038/srep32101. View

13.

Imaduwage K, Lakbub J, Go E, Desaire H . Rapid LC-MS Based High-Throughput Screening Method, Affording No False Positives or False Negatives, Identifies a New Inhibitor for Carbonic Anhydrase. Sci Rep. 2017; 7(1):10324. PMC: 5583356. DOI: 10.1038/s41598-017-08602-w. View

14.

Hopfinger A . Computer-assisted drug design. J Med Chem. 1985; 28(9):1133-9. DOI: 10.1021/jm00147a001. View

15.

Kleandrova V, Speck-Planche A . The QSAR Paradigm in Fragment-Based Drug Discovery: From the Virtual Generation of Target Inhibitors to Multi-Scale Modeling. Mini Rev Med Chem. 2020; 20(14):1357-1374. DOI: 10.2174/1389557520666200204123156. View

16.

Miyake Y, Itoh Y, Hatanaka A, Suzuma Y, Suzuki M, Kodama H . Identification of novel lysine demethylase 5-selective inhibitors by inhibitor-based fragment merging strategy. Bioorg Med Chem. 2019; 27(6):1119-1129. DOI: 10.1016/j.bmc.2019.02.006. View

17.

Letunic I, Khedkar S, Bork P . SMART: recent updates, new developments and status in 2020. Nucleic Acids Res. 2020; 49(D1):D458-D460. PMC: 7778883. DOI: 10.1093/nar/gkaa937. View

18.

Schneider G, Fechner U . Computer-based de novo design of drug-like molecules. Nat Rev Drug Discov. 2005; 4(8):649-63. DOI: 10.1038/nrd1799. View

19.

Svetnik V, Liaw A, Tong C, Culberson J, Sheridan R, Feuston B . Random forest: a classification and regression tool for compound classification and QSAR modeling. J Chem Inf Comput Sci. 2003; 43(6):1947-58. DOI: 10.1021/ci034160g. View

20.

Mansour N, Paveley R, Gardner J, Bell A, Parkinson T, Bickle Q . High Throughput Screening Identifies Novel Lead Compounds with Activity against Larval, Juvenile and Adult Schistosoma mansoni. PLoS Negl Trop Dis. 2016; 10(4):e0004659. PMC: 4851381. DOI: 10.1371/journal.pntd.0004659. View