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Journals / Türk Biyokimya Dergisi / 2019 / Cilt: 44 - Sayı: 3

Computational exploration of antiviral activity of phytochemicals against NS2B/NS3 proteases from dengue virus

Dang Virüs’den NS2B/NS3 proteazlarına karşı fitokimyasalların antiviral aktivitesinin hesaplamalı olarak araştırılması

Muneeba WASEEM
Waqar HUSSAIN
Nouman RASOOL
Aisha ASHRAF
Sajid MAHMOOD
Pages
261–277
Publication Date
2022-11-04
DOI
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Erycristagallin and Osajin fromErythrina variegate, PapraineA from Fumaria indica andAloe-Emodin from Aloe vera are the most potent inhibitorsof NS2B/NS3 protease from DENV1, DENV2, DENV3and DENV4, having binding affinities of −9.6 kcal/mol, −9.6 kcal/mol, −9.6 kcal/mol and −9.2 kcal/mol,respectively.Conclusion: The effective drug-like properties of all 18 phytochemicalsdemonstrate the inhibition potential againstdengue virus replication in human beings.

📌 3 Key Takeaways

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Objective & Hypothesis:Background: Dengue fever has emerged as a serious threatin Pakistan in the last few years with high morbidity ratesand substantial mortality.
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Key Findings & Data:In the present study, NS2B/NS3protease from four dengue virus (DENV) serotypes havebeen targeted using 2350 phytochemicals from variousmedicinal plants.Material and methods: The phytochemicals were subjectedto docking against NS2B/NS3 proteases using AutoDockVina focusing the binding site, and the binding energieswere determined to screen the effectively docked phytochemicals.Pharmacological properties were also analyzedfor all the phytochemicals using PreADMET web server.Results: Binding affinities ranged from −4.0 to –9.8kcal/mol and a threshold of −9.0 kcal/mol was appliedfor screening compounds.
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Conclusion & Impact:Erycristagallin and Osajin fromErythrina variegate, PapraineA from Fumaria indica andAloe-Emodin from Aloe vera are the most potent inhibitorsof NS2B/NS3 protease from DENV1, DENV2, DENV3and DENV4, having binding affinities of −9.6 kcal/mol, −9.6 kcal/mol, −9.6 kcal/mol and −9.2 kcal/mol,respectively.Conclusion: The effective drug-like properties of all 18 phytochemicalsdemonstrate the inhibition potential againstdengue virus replication in human beings.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Domain Parameters

Abstract

Background: Dengue fever has emerged as a serious threatin Pakistan in the last few years with high morbidity ratesand substantial mortality. In the present study, NS2B/NS3protease from four dengue virus (DENV) serotypes havebeen targeted using 2350 phytochemicals from variousmedicinal plants.Material and methods: The phytochemicals were subjectedto docking against NS2B/NS3 proteases using AutoDockVina focusing the binding site, and the binding energieswere determined to screen the effectively docked phytochemicals.Pharmacological properties were also analyzedfor all the phytochemicals using PreADMET web server.Results: Binding affinities ranged from −4.0 to –9.8kcal/mol and a threshold of −9.0 kcal/mol was appliedfor screening compounds. A total of 18 phytochemicalsare screened for passing all evaluation criteria of adrug in which three were for DENV1-NS2B/NS3, five forDENV2-NS2B/NS3, six for DENV3-NS2B/NS3 and fourfor DENV4-NS2B/NS3. Erycristagallin and Osajin fromErythrina variegate, PapraineA from Fumaria indica andAloe-Emodin from Aloe vera are the most potent inhibitorsof NS2B/NS3 protease from DENV1, DENV2, DENV3and DENV4, having binding affinities of −9.6 kcal/mol, −9.6 kcal/mol, −9.6 kcal/mol and −9.2 kcal/mol,respectively.Conclusion: The effective drug-like properties of all 18 phytochemicalsdemonstrate the inhibition potential againstdengue virus replication in human beings.

Özet

Amaç: Dang humması, son birkaç yılda yüksek morbidite oranları ve ciddi mortalite ile Pakistan’da ciddi bir tehdit olarak ortaya çıkmıştır. Bu çalışmada, dört dang virüsü (DENV) serotipinden NS2B/NS3 proteazı, çeşitli tıbbi bitkilerden alınan 2350 fitokimyasal kullanılarak hedeflenmiştir. Gereç ve Yöntemler: Fitokimyasallar, bağlanma alanına odaklanan AutoDock Vina kullanılarak NS2B/NS3 proteazlarına karşı kenetlenmeye tabi tutuldu ve etkin şekilde kenetlenmiş fitokimyasalları taramak için bağlanma enerjileri belirlendi. Farmakolojik özellikler ayrıca PreADMET analiz edildi. Bulgular: Bileşikleri taramak için bağlanma afiniteleri −4.0 ila −9.8 kcal/mol arasında ve eşik −9.0 kcal/mol olarak uygulanmıştır. Toplam 18 fitokimyasal bir ilacın tüm değerlendirme kriterlerini geçmesi için tarandı; 3’ü DENV1-NS2B/NS3 için, 5’i DENV2-NS2B/NS3 için, 6’sı DENV3-NS2B/NS3 için ve 4’ü DENV4-NS2B/NS3 içindi. Erythrina variegate’den Erycristagallin ve Osajin, Fumaria indica’dan PapraineA ve Aloe vera’dan Aloe-Emodin, sırasıyla −9.6 kcal/mol, −9.6 kcal/mol, −9.6 kcal/mol ve −9.2 kcal/ mol, bağlanma afiniteleri ile DENV1, DENV2, DENV3 ve DENV4’ten NS2B/NS3 proteazının en güçlü inhibitörleridir. Sonuç: Tüm 18 fitokimyasal maddenin etkin ilaç benzeri özellikleri, insanlardaki dang virüsü replikasyonuna karşı inhibisyon potansiyelini göstermektedir.

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Cite This Article

WASEEM, M., HUSSAIN, W., RASOOL, N., ASHRAF, A., MAHMOOD, S. (2022). Computational exploration of antiviral activity of phytochemicals against NS2B/NS3 proteases from dengue virus. Türk Biyokimya Dergisi, Cilt: 44 - Sayı: 3, 261–277. https://ajindex.com/articles/620896

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References (14)

  1. Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, et al. The global distribution and burden of dengue. Nature 2013;496:504–7
  2. Añez G, Heisey DA, Volkova E, Rios M. Complete genome sequences of dengue virus type 1 to 4 strains used for the development of CBER/FDA RNA reference reagents and WHO International Standard candidates for nucleic acid testing. Genome Announc 2016;4:1583–98
  3. Mustafa MS, Rasotgi V, Jain S, Gupta V. Discovery of fifth serotype of dengue virus (DENV-5): a new public health dilemma in dengue control. Med J Armed Forces India 2015;71:67–70
  4. Normile D. Surprising new dengue virus throws a spanner in disease control efforts. Science 2013;342:415
  5. Endy TP, Anderson KB, Nisalak A, Yoon IK, Green S, Rothman AL, et al. Determinants of inapparent and symptomatic dengue infection in a prospective study of primary school children in Kamphaeng Phet, Thailand. PLoSNegl Trop Dis 2011;5:e975
  6. Qaddir I, Rasool N, Hussain W, Mahmood S. Computer-aided analysis of phytochemicals as potential dengue virus inhibitors based on molecular docking, ADMET and DFT studies. J Vector Borne Dis 2017;54:140
  7. Messer WB, Gubler DJ, Harris E, Sivananthan K, De Silva AM. Emergence and global spread of a dengue serotype 3, subtype III virus. Emerg Infect Dis 2003;9:800–9
  8. Murthy HK, Clum S, Padmanabhan R. Dengue virus NS3 serine protease. Crystal structure and insights into interaction of the active site with substrates by molecular modeling and structural analysis of mutational effects. J Biol Chem 2009;284:34468
  9. Bera AK, Kuhn RJ, Smith JL. Functional characterization of cis and trans activity of the Flavivirus NS2B-NS3 protease. J Biol Chem 2007;282:12883–92
  10. Chandramouli S, Joseph JS, Daudenarde S, Gatchalian J, Cornillez-Ty C, Kuhn P. Serotype-specific structural differences in the protease-cofactor complexes of the dengue virus family. J Virol 2010;84:3059–67
  11. Aguiar M, Stollenwerk N, Halstead SB. The risks behind Dengvaxia recommendation. Lancet Infect Dis 2016;16:882
  12. Erbel P, Schiering N, D’Arcy A, Renatus M, Kroemer M, Lim SP, et al. Structural basis for the activation of flaviviral NS3 proteases from dengue and West Nile virus. Nat Struct Mol Biol 2006;13:372–4
  13. Noble CG, Seh CC, Chao AT, Shi PY. Ligand-bound structures of the dengue virus protease reveal the active conformation. J Virol 2012;86:438–46
  14. Luo D, Xu T, Hunke C, Grüber G, Vasudevan SG, Lescar J. Crystal structure of the NS3 protease-heli