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Molecular docking and drug-likeness study of nirmatrelvir as promising drug candidates of dengue virus NS2B-NS3 protease

Yıl 2023, Cilt: 27 Sayı: 5, 1760 - 1767, 28.06.2025

Akm Moyeenul Huq Miah Roney Saiful Nizam Tajuddin Mohd Fadhlizil Fasihi Mohd Aluwi

Öz

Aedes aegypti is the primary vector for the transmission of the dengue virus (DENV), which causes dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). There is now no antiviral medication available to treat DENV, which kills thousands of people year and infects millions of individuals. Due to the current situation, effective and useful treatments for this virus urgently need to be developed. Therefore, the goal of the current work was to determine, using molecular docking and drug-likeness analysis, the anti-viral potential of Nirmatrelvir inhibitor against DENV (1-4) NS2B-NS3 protease. Nirmatrelvir shown robust and stable bonding in the binding pocket of DENV (1-4) NS2B-NS3 protease, as demonstrated by molecular docking. According to the drug-likeness study, Nirmatrelvir shown druggability and may function as possible inhibitor to halt DENV proliferation. To establish their action and other qualities, it is also necessary to research how substances behave in both in-vitro and in-vivo settings.

Anahtar Kelimeler

Nirmatrelvir anti-dengue NS2B/NS3 protease molecular docking drug-likeness

Kaynakça

  • [1] Qamar MT, Ashfaq UA, Tusleem K, Mumtaz A, Tariq Q, Goheer A, Ahmed B. In-silico identification and evaluation of plant flavonoids as dengue NS2B/NS3 protease inhibitors using molecular docking and simulation approach. Pak J Pharm Sci. 2017; 30(6): 2119-2137.
  • [2] Roney M, Huq AM, Rullah K, Hamid HA, Imran S, Islam MA, Mohd Aluwi MFF. Virtual screening-based identification of potent DENV-3 RdRp protease inhibitors via in-house usnic acid derivative database. J Comput Biophys Chem. 2021; 20(08): 797-814. https://doi.org/10.1142/S2737416521500496
  • [3] World Health Organization. Comprehensive guideline for prevention and control of dengue and dengue haemorrhagic fever. 2021. https://apps.who.int/iris/handle/10665/204894 (accessed on- -2023)
  • [4] Lim SYM, Chieng JY, Pan Y. Recent insights on anti-dengue virus (DENV) medicinal plants: Review on in vitro, in vivo and in silico discoveries. All Life. 2021; 14(1): 1-33. https://doi.org/10.1080/26895293.2020.1856192
  • [5] Astuti I. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response. Diabetes Metab Syndr: Clin Res Rev. 2020; 14(4): 407-412. https://doi.org/10.1016/j.dsx.2020.04.020
  • [6] Chappell KJ, Stoermer MJ, Fairlie DP, Young PR. West Nile Virus NS2B/NS3 protease as an antiviral target. Curr Med Chem. 2008; 15(27): 2771-2784. https://doi.org/10.2174/092986708786242804
  • [7] Birabaharan M, Martin TC. Acute pulmonary emboli following rebound phenomenon after Nirmatrelvir/Ritonavir treatment for COVID-19. Am J Emerg Med. 2022; 61: 235.e5-236.e6. https://doi.org/10.1016/j.ajem.2022.08.012
  • [8] Wanounou M, Caraco Y, Levy RH, Bialer M, Perucca E. Clinically relevant interactions between ritonavir-boosted nirmatrelvir and concomitant antiseizure medications: implications for the management of COVID-19 in patients with epilepsy. Clin Pharmacokinet. 2022; 61(9): 1219-1236. https://doi.org/10.1007/s40262-022-01152-z
  • [9] Hasan MR, Alsaiari AA, Fakhurji BZ, Molla MHR, Asseri AH, Sumon MAA, Kim B. Application of mathematical modeling and computational tools in the modern drug design and development process. Molecules. 2022; 27(13): 4169. https://doi.org/10.3390/molecules27134169
  • [10] Agarwal S, Mehrotra RJJC. An overview of molecular docking. JSM Chem. 2016; 4(2): 1024-1028.
  • [11] Lin X, Li X, Lin X. A review on applications of computational methods in drug screening and design. Molecules. 2020; 25(6): 1375. https://doi.org/10.3390/molecules25061375
  • [12] Kiat TS, Pippen R, Yusof R, Ibrahim H, Khalid N, Abd Rahman N. Inhibitory activity of cyclohexenyl chalcone derivatives and flavonoids of fingerroot, Boesenbergia rotunda (L.), towards dengue-2 virus NS3 protease. Bioorg Med Chem Lett. 2006; 16(12): 3337-3340. https://doi.org/10.1371/journal.pone.0210869
  • [13] Hariono M, Choi SB, Roslim RF, Nawi MS, Tan ML, Kamarulzaman EE, Wahab HA. Thioguanine-based DENV-2 NS2B/NS3 protease inhibitors: Virtual screening, synthesis, biological evaluation and molecular modelling. PloS one. 2019; 14(1): e0210869. https://doi.org/10.1371/journal.pone.0210869
  • [14] Mishra PM, Nandi CK. Structural decoding of a small molecular inhibitor on the binding of SARS-CoV-2 to the ACE 2 receptor. J Phys Chem B. 2021; 125(30): 8395-8405. https://doi.org/10.1021/acs.jpcb.1c03294
  • [15] Padhi AK, Seal A, Khan JM, Ahamed M, Tripathi T. Unraveling the mechanism of arbidol binding and inhibition of SARS-CoV-2: Insights from atomistic simulations. Eur J Pharmacol. 2021; 894: 173836. https://doi.org/10.1016/j.ejphar.2020.173836
  • [16] Liu Y, Grimm M, Dai WT, Hou MC, Xiao ZX, Cao Y. CB-Dock: a web server for cavity detection-guided protein–ligand blind docking. Acta Pharmacol Sin. 2020; 41(1): 138-144. https://doi.org/10.1038/s41401-019-0228-6
  • [17] Hao G, Dong Q, Yang G. A comparative study on the constitutive properties of marketed pesticides. Mol Inform. 2011; 30(6-7): 614-622. https://doi.org/10.1002/minf.201100020
  • [18] Roney M, Hossain MS, Aluwi MFFM. In silico analysis for discovery of dengue virus inhibitor from natural compounds. ICB-Pharma 2023, AHCPS 3. 2023; 379–388. https://doi.org/10.2991/978-94-6463-050-3_33.
  • [19] Giaginis C, Tsantili-Kakoulidou A. Alternative measures of lipophilicity: from octanol–water partitioning to IAM retention. J Pharm Sci. 2008; 97(8): 2984-3004. https://doi.org/10.1002/jps.21244
  • [20] Arnott JA, Planey SL. The influence of lipophilicity in drug discovery and design. Exp Opin Drug Dis. 2012; 7(10): 863-875. https://doi.org/10.1517/17460441.2012.714363
  • [21] Hughes JD, Blagg J, Price DA, Bailey S, De CrescenzoGA, Devraj RV, Zhang Y. Physiochemical drug properties associated with in vivo toxicological outcomes. Bioorg Med Chem Lett. 2008; 18(17): 4872-4875. https://doi.org/10.1016/j.bmcl.2008.07.071
  • [22] 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(6): 3059-3067. https://doi.org/10.1128/JVI.02044-09
  • [23] Erbel P, Schiering N, D'Arcy A, Renatus M, Kroemer M, Lim SP, Hommel U. Structural basis for the activation of flaviviral NS3 proteases from dengue and West Nile virus. Nat Struct Mol Biol. 2006; 13(4): 372-373. https://doi.org/10.1038/nsmb1073
  • [24] Noble CG, Seh CC, Chao AT, Shi PY. Ligand-bound structures of the dengue virus protease reveal the active conformation. J Virol. 2012; 86(1): 438-446. https://doi.org/10.1128/JVI.06225-11
  • [25] Luo D, Xu T, Hunke C, Gruber G, Vasudevan SG, Lescar J. Crystal structure of the NS3 protease-helicase from dengue virus. J Virol. 2008; 82(1): 173-183. https://doi.org/10.1128/JVI.01788-07
  • [26] Roney M, Aluwi MFFM, Laman F, Bhuiyan MA, Huq AM. Molecular docking and in silico evaluation of phytochemicals of bioactive methanolic extract of Ipomoea mauritiana Jacq. as anti-bacterial agents. J Comput Biophys Chem. 2022; 21(5): 499-513. https://doi.org/10.1142/S2737416522500168

Yıl 2023, Cilt: 27 Sayı: 5, 1760 - 1767, 28.06.2025

Akm Moyeenul Huq Miah Roney Saiful Nizam Tajuddin Mohd Fadhlizil Fasihi Mohd Aluwi

Öz

Kaynakça

  • [1] Qamar MT, Ashfaq UA, Tusleem K, Mumtaz A, Tariq Q, Goheer A, Ahmed B. In-silico identification and evaluation of plant flavonoids as dengue NS2B/NS3 protease inhibitors using molecular docking and simulation approach. Pak J Pharm Sci. 2017; 30(6): 2119-2137.
  • [2] Roney M, Huq AM, Rullah K, Hamid HA, Imran S, Islam MA, Mohd Aluwi MFF. Virtual screening-based identification of potent DENV-3 RdRp protease inhibitors via in-house usnic acid derivative database. J Comput Biophys Chem. 2021; 20(08): 797-814. https://doi.org/10.1142/S2737416521500496
  • [3] World Health Organization. Comprehensive guideline for prevention and control of dengue and dengue haemorrhagic fever. 2021. https://apps.who.int/iris/handle/10665/204894 (accessed on- -2023)
  • [4] Lim SYM, Chieng JY, Pan Y. Recent insights on anti-dengue virus (DENV) medicinal plants: Review on in vitro, in vivo and in silico discoveries. All Life. 2021; 14(1): 1-33. https://doi.org/10.1080/26895293.2020.1856192
  • [5] Astuti I. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response. Diabetes Metab Syndr: Clin Res Rev. 2020; 14(4): 407-412. https://doi.org/10.1016/j.dsx.2020.04.020
  • [6] Chappell KJ, Stoermer MJ, Fairlie DP, Young PR. West Nile Virus NS2B/NS3 protease as an antiviral target. Curr Med Chem. 2008; 15(27): 2771-2784. https://doi.org/10.2174/092986708786242804
  • [7] Birabaharan M, Martin TC. Acute pulmonary emboli following rebound phenomenon after Nirmatrelvir/Ritonavir treatment for COVID-19. Am J Emerg Med. 2022; 61: 235.e5-236.e6. https://doi.org/10.1016/j.ajem.2022.08.012
  • [8] Wanounou M, Caraco Y, Levy RH, Bialer M, Perucca E. Clinically relevant interactions between ritonavir-boosted nirmatrelvir and concomitant antiseizure medications: implications for the management of COVID-19 in patients with epilepsy. Clin Pharmacokinet. 2022; 61(9): 1219-1236. https://doi.org/10.1007/s40262-022-01152-z
  • [9] Hasan MR, Alsaiari AA, Fakhurji BZ, Molla MHR, Asseri AH, Sumon MAA, Kim B. Application of mathematical modeling and computational tools in the modern drug design and development process. Molecules. 2022; 27(13): 4169. https://doi.org/10.3390/molecules27134169
  • [10] Agarwal S, Mehrotra RJJC. An overview of molecular docking. JSM Chem. 2016; 4(2): 1024-1028.
  • [11] Lin X, Li X, Lin X. A review on applications of computational methods in drug screening and design. Molecules. 2020; 25(6): 1375. https://doi.org/10.3390/molecules25061375
  • [12] Kiat TS, Pippen R, Yusof R, Ibrahim H, Khalid N, Abd Rahman N. Inhibitory activity of cyclohexenyl chalcone derivatives and flavonoids of fingerroot, Boesenbergia rotunda (L.), towards dengue-2 virus NS3 protease. Bioorg Med Chem Lett. 2006; 16(12): 3337-3340. https://doi.org/10.1371/journal.pone.0210869
  • [13] Hariono M, Choi SB, Roslim RF, Nawi MS, Tan ML, Kamarulzaman EE, Wahab HA. Thioguanine-based DENV-2 NS2B/NS3 protease inhibitors: Virtual screening, synthesis, biological evaluation and molecular modelling. PloS one. 2019; 14(1): e0210869. https://doi.org/10.1371/journal.pone.0210869
  • [14] Mishra PM, Nandi CK. Structural decoding of a small molecular inhibitor on the binding of SARS-CoV-2 to the ACE 2 receptor. J Phys Chem B. 2021; 125(30): 8395-8405. https://doi.org/10.1021/acs.jpcb.1c03294
  • [15] Padhi AK, Seal A, Khan JM, Ahamed M, Tripathi T. Unraveling the mechanism of arbidol binding and inhibition of SARS-CoV-2: Insights from atomistic simulations. Eur J Pharmacol. 2021; 894: 173836. https://doi.org/10.1016/j.ejphar.2020.173836
  • [16] Liu Y, Grimm M, Dai WT, Hou MC, Xiao ZX, Cao Y. CB-Dock: a web server for cavity detection-guided protein–ligand blind docking. Acta Pharmacol Sin. 2020; 41(1): 138-144. https://doi.org/10.1038/s41401-019-0228-6
  • [17] Hao G, Dong Q, Yang G. A comparative study on the constitutive properties of marketed pesticides. Mol Inform. 2011; 30(6-7): 614-622. https://doi.org/10.1002/minf.201100020
  • [18] Roney M, Hossain MS, Aluwi MFFM. In silico analysis for discovery of dengue virus inhibitor from natural compounds. ICB-Pharma 2023, AHCPS 3. 2023; 379–388. https://doi.org/10.2991/978-94-6463-050-3_33.
  • [19] Giaginis C, Tsantili-Kakoulidou A. Alternative measures of lipophilicity: from octanol–water partitioning to IAM retention. J Pharm Sci. 2008; 97(8): 2984-3004. https://doi.org/10.1002/jps.21244
  • [20] Arnott JA, Planey SL. The influence of lipophilicity in drug discovery and design. Exp Opin Drug Dis. 2012; 7(10): 863-875. https://doi.org/10.1517/17460441.2012.714363
  • [21] Hughes JD, Blagg J, Price DA, Bailey S, De CrescenzoGA, Devraj RV, Zhang Y. Physiochemical drug properties associated with in vivo toxicological outcomes. Bioorg Med Chem Lett. 2008; 18(17): 4872-4875. https://doi.org/10.1016/j.bmcl.2008.07.071
  • [22] 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(6): 3059-3067. https://doi.org/10.1128/JVI.02044-09
  • [23] Erbel P, Schiering N, D'Arcy A, Renatus M, Kroemer M, Lim SP, Hommel U. Structural basis for the activation of flaviviral NS3 proteases from dengue and West Nile virus. Nat Struct Mol Biol. 2006; 13(4): 372-373. https://doi.org/10.1038/nsmb1073
  • [24] Noble CG, Seh CC, Chao AT, Shi PY. Ligand-bound structures of the dengue virus protease reveal the active conformation. J Virol. 2012; 86(1): 438-446. https://doi.org/10.1128/JVI.06225-11
  • [25] Luo D, Xu T, Hunke C, Gruber G, Vasudevan SG, Lescar J. Crystal structure of the NS3 protease-helicase from dengue virus. J Virol. 2008; 82(1): 173-183. https://doi.org/10.1128/JVI.01788-07
  • [26] Roney M, Aluwi MFFM, Laman F, Bhuiyan MA, Huq AM. Molecular docking and in silico evaluation of phytochemicals of bioactive methanolic extract of Ipomoea mauritiana Jacq. as anti-bacterial agents. J Comput Biophys Chem. 2022; 21(5): 499-513. https://doi.org/10.1142/S2737416522500168
Toplam 26 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Eczacılık ve İlaç Bilimleri (Diğer)
Bölüm Articles
Yazarlar

Akm Moyeenul Huq 0000-0001-9437-9821

Miah Roney 0000-0003-2512-0837

Saiful Nizam Tajuddin 0000-0003-1223-8203

Mohd Fadhlizil Fasihi Mohd Aluwi 0000-0003-0729-768X

Yayımlanma Tarihi 28 Haziran 2025
Yayımlandığı Sayı Yıl 2023 Cilt: 27 Sayı: 5

Kaynak Göster

APA Huq, A. M., Roney, M., Tajuddin, S. N., Aluwi, M. F. F. M. (2025). Molecular docking and drug-likeness study of nirmatrelvir as promising drug candidates of dengue virus NS2B-NS3 protease. Journal of Research in Pharmacy, 27(5), 1760-1767.
AMA Huq AM, Roney M, Tajuddin SN, Aluwi MFFM. Molecular docking and drug-likeness study of nirmatrelvir as promising drug candidates of dengue virus NS2B-NS3 protease. J. Res. Pharm. Temmuz 2025;27(5):1760-1767.
Chicago Huq, Akm Moyeenul, Miah Roney, Saiful Nizam Tajuddin, ve Mohd Fadhlizil Fasihi Mohd Aluwi. “Molecular Docking and Drug-Likeness Study of Nirmatrelvir As Promising Drug Candidates of Dengue Virus NS2B-NS3 Protease”. Journal of Research in Pharmacy 27, sy. 5 (Temmuz 2025): 1760-67.
EndNote Huq AM, Roney M, Tajuddin SN, Aluwi MFFM (01 Temmuz 2025) Molecular docking and drug-likeness study of nirmatrelvir as promising drug candidates of dengue virus NS2B-NS3 protease. Journal of Research in Pharmacy 27 5 1760–1767.
IEEE A. M. Huq, M. Roney, S. N. Tajuddin, ve M. F. F. M. Aluwi, “Molecular docking and drug-likeness study of nirmatrelvir as promising drug candidates of dengue virus NS2B-NS3 protease”, J. Res. Pharm., c. 27, sy. 5, ss. 1760–1767, 2025.
ISNAD Huq, Akm Moyeenul vd. “Molecular Docking and Drug-Likeness Study of Nirmatrelvir As Promising Drug Candidates of Dengue Virus NS2B-NS3 Protease”. Journal of Research in Pharmacy 27/5 (Temmuz 2025), 1760-1767.
JAMA Huq AM, Roney M, Tajuddin SN, Aluwi MFFM. Molecular docking and drug-likeness study of nirmatrelvir as promising drug candidates of dengue virus NS2B-NS3 protease. J. Res. Pharm. 2025;27:1760–1767.
MLA Huq, Akm Moyeenul vd. “Molecular Docking and Drug-Likeness Study of Nirmatrelvir As Promising Drug Candidates of Dengue Virus NS2B-NS3 Protease”. Journal of Research in Pharmacy, c. 27, sy. 5, 2025, ss. 1760-7.
Vancouver Huq AM, Roney M, Tajuddin SN, Aluwi MFFM. Molecular docking and drug-likeness study of nirmatrelvir as promising drug candidates of dengue virus NS2B-NS3 protease. J. Res. Pharm. 2025;27(5):1760-7.