DRUG REPURPOSING OF COMMERCIALLY AVAILABLE AZOLES AGAINST ASPERGILLOSIS PEROXIREDOXIN ASP F3 ALLERGEN DRUGS
DOI:
https://doi.org/10.22159/ijms.2023.v11i2.47142Keywords:
Drug repurposing, Azoles, Aspergillosis, Molecular docking, ADMETAbstract
Objectives: Aspergillus peroxiredoxin is a significant contributor to a multitude of infections in both humans and animals infecting the respiratory system due to which lungs related illnesses and fatalities continue around the globe. This research examines various antifungal drugs which are effective against aspergillus.
Methods: The present study implements computational methods to assess the effectiveness of several phytochemicals toward the A. peroxiredoxin protein PyRx, the virtual screening tool was used to systematically perform molecular docking. It was done so to test the binding affinity with A. peroxiredoxin protein 5J9B, 10 phytocompounds were selected from Azole Antifungals which was based on previous knowledge. Using ADMET filters, the pharmacological evaluation of the ligands was performed.
Results: The ligands flutrimazole, clotrimazole, fluconazole, sertaconazole, and bifonazole demonstrated the best binding with the target protein peroxiredoxin Asp f3.
Conclusion: The broad-spectrum anti-fungal drug Flutrimazole demonstrated the least binding and best pharmacological parameters with the target proteins. This drug can be repurposed for other fungal infections.
References
Fernandez-Pittol M, Alejo-Cancho I, Rubio-García E, Cardozo C, Puerta-Alcalde P, Moreno-García E, et al. Aspergillosis by cryptic Aspergillus species: A case series and review of the literature. Rev Iberoam Micol 2022;39:44-9.
Kousha M, Tadi R, Soubani AO. Pulmonary aspergillosis: A clinical review. Eur Respir Rev 2011;20:156-74.
Cadena J, Thompson GR 3rd, Patterson TF. Invasive aspergillosis: Current strategies for diagnosis and management. Infect Dis Clin North Am 2016;30:125-42.
Latgé JP, Chamilos G. Aspergillus fumigatus and aspergillosis in 2019. Clin Microbiol Rev 2019;33:e00140-18.
Brantl V, Boysen JM, Yap A, Golubtsov E, Ruf D, Heinekamp T, et al. Peroxiredoxin Asp f3 is essential for Aspergillus fumigatus to overcome iron limitation during infection. mBio 2021;12:e0097621.
Hillmann F, Bagramyan K, Straßburger M, Heinekamp T, Hong TB, Bzymek KP, et al. The crystal structure of peroxiredoxin asp f3 provides mechanistic insight into oxidative stress resistance and virulence of Aspergillus fumigatus. Sci Rep 2016;6:33396.
Parvathaneni V, Kulkarni NS, Muth A, Gupta V. Drug repurposing: A promising tool to accelerate the drug discovery process. Drug Discov Today 2019;24:2076-85.
Baker NC, Ekins S, Williams AJ, Tropsha A. A bibliometric review of drug repurposing. Drug Discov Today 2018;23:661-72.
Pushpakom S, Iorio F, Eyers PA, Escott KJ, Hopper S, Wells A, et al. Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov 2019;18:41-58.
Kim JH, Cheng LW, Chan KL, Tam CC, Mahoney N, Friedman M, et al. Antifungal drug repurposing. Antibiotics (Basel) 2020;9:812.
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, et al. DrugBank 5.0: A major update to the DrugBank database for 2018. Nucleic Acids Res 2018;46:D1074-82.
Kim S, Chen J, Cheng T, Gindulyte A, He J, He S, et al. PubChem 2019 update: Improved access to chemical data. Nucleic Acids Res 2019;47:D1102-9.
Burley SK, Berman HM, Kleywegt GJ, Markley JL, Nakamura H, Velankar S. Protein data bank (PDB): The single global macromolecular structure archive. Methods Mol Biol 2017;1607:627-41.
Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, et al. SWISS-MODEL: Homology modelling of protein structures and complexes. Nucleic Acids Res 2018;46:W296-303.
Jejurikar BL, Rohane SH. Drug designing in discovery studio. Asian J Res Chem 2021;14:135-8.
Zhou AQ, O’Hern CS, Regan L. Revisiting the Ramachandran plot from a new angle. Protein Sci 2011;20:1166-71.
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;7:42717.
Yang H, Lou C, Sun L, Li J, Cai Y, Wang Z, et al. admetSAR 2.0: Web-service for prediction and optimization of chemical ADMET properties. Bioinformatics 2019;35:1067-9.
Kondapuram SK, Sarvagalla S, Coumar MS. Docking-based virtual screening using PyRx Tool: Autophagy target Vps34 as a case study. In: Molecular Docking for Computer-aided Drug Design. Amsterdam, Netherlands: Elsevier; 2021. p. 463-77.
Alomar A, Videla S, Delgadillo J, Gich I, Izquierdo I, Forn J. Flutrimazole 1% dermal cream in the treatment of dermatomycoses: A multicentre, double-blind, randomized, comparative clinical trial with bifonazole 1% cream. Efficacy of flutrimazole 1% dermal cream in dermatomycoses. Catalan Flutrimazole study group. Dermatology 1995;190:295-300.
Binet O, Soto-Melo J, Delgadillo J, Videla S, Izquierdo I, Forn J. Flutrimazole 1% dermal cream in the treatment of dermatomycoses: A randomized, multicentre, double-blind, comparative clinical trial with 1% clotrimazole cream. Mycoses 1994;37:455-9.
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