An Insilico Investigation: Repurposing FDA Approved Drugs Targeting Monkeypox Virus


Authors : Surendhar P.; Varshini E.; Vinoth Kumar S.; Uma T.; Nepoleon R.; Rajamohamed H.; Mohamed Akram Ali S.

Volume/Issue : Volume 10 - 2025, Issue 10 - October

Google Scholar : https://tinyurl.com/2sb9ckw5

Scribd : https://tinyurl.com/65k2xs6b

DOI : https://doi.org/10.38124/ijisrt/25oct382

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Abstract : Monkeypox viral infection is emerging as a significant threat and concern worldwide for the human population. Still, the available treatment options don’t meet the requirement, increasing the mortality and morbidity. This fosters the researchers to engage in the development of novel treatment strategies or drug repurposing to overcome the hurdle. With this background, the identification of potential drug targets can significantly amplify the development of potent drug molecules for the treatment. The proteins responsible for viral replication should be targeted, and hindering these proteins should be the key findings to reduce the morbidity and mortality. The literature review provides insight into two viral proteins, viral core Thymidylate Kinase (2V54) and DNA polymerase holoenzyme (8HG1), which are primarily responsible for disease aggravation. Sixty-four antiviral agents approved by the FDA were selected and evaluated against both viral proteins via simulation screening. These antiviral agents possess the capability to obstruct bacterial protein production, rendering them significant candidates for medication repurposing. According to the screening outcomes against DNA polymerase holoenzyme, the two leading compounds, Dolutegravir and Raltegravir, with docking values of – 10.0 and –9.7 kcal/mol, respectively, were chosen for further examination. Raltegravir and Etavirine, exhibiting docking scores of −10.0 and −9.6 kcal/mol, respectively, against thymidine kinase are the leading compounds identified following the validation of the protease with the pharmacological library. While investigating medications targeting proteinase, the top two molecules, Dolutegravir and Raltegravir, had the highest docking scores. These two medicinal compounds have significant inhibitory capabilities against MPXV proteinase Thymidine kinase and DNA polymerase protein. Ultimately, the current research illustrates the repurposing of antiviral medicines as a treatment for monkeypox viral infection.

Keywords : Monkeypox Virus, Thymidylate Kinase, DNA Polymerase Holoenzyme, Antiviral Agents.

References :

  1. Jafari K, Woodward GA. Mpox. Pediatr Emerg Care. 2023 Nov 1;39(11):883-889. doi: 10.1097/PEC.0000000000003063. PMID: 37902655.
  2. Petersen E, Kantele A, Koopmans M, Asogun D, Yinka-Ogunleye A, Ihekweazu C, Zumla A. Human Monkeypox: Epidemiologic and Clinical Characteristics, Diagnosis, and Prevention. Infect Dis Clin North Am. 2019 Dec;33(4):1027-1043. doi: 10.1016/j.idc.2019.03.001. Epub 2019 Apr 11. PMID: 30981594; PMCID: PMC9533922.
  3. Louten J. Virus Structure and Classification. Essential Human Virology. 2016:19 29. doi: 10.1016/B978-0-12-800947-5.00002-8. Epub 2016 May 6. PMCID: PMC7150055.
  4. Mitjà O, Ogoina D, Titanji BK, Galvan C, Muyembe JJ, Marks M, Orkin CM. Monkeypox. Lancet. 2023 Jan 7;401(10370):60-74. doi: 10.1016/S0140-6736(22)02075-X. Epub 2022 Nov 17. Erratum in: Lancet. 2022 Dec 3;400(10367):1926. doi: 10.1016/S0140-6736(22)02414-X. PMID: 36403582; PMCID: PMC9671644.
  5. Singhal T, Kabra SK, Lodha R. Monkeypox: A Review. Indian J Pediatr. 2022 Oct;89(10):955-960. doi: 10.1007/s12098-022-04348-0. Epub 2022 Aug 10. PMID: 35947269; PMCID: PMC9363855.
  6. KAMARIA, P., & GUHA.. A REVIEW ON MONKEYPOX DISEASE. Innovare Journal Health Sciences, 2022;11(1): 1–5. https://doi.org/10.22159/ijhs.2022.v11i1.46559
  7. Soheili M, Nasseri S, Afraie M, Khateri S, Moradi Y, Mahdavi Mortazavi SM, Gilzad-Kohan H. Monkeypox: Virology, Pathophysiology, Clinical Characteristics, Epidemiology, Vaccines, Diagnosis, and Treatments. J Pharm Pharm Sci. 2022;25:297-322. doi: 10.18433/jpps33138. PMID: 36130588.
  8. Sawale Amol V, Ashwini K. Bhilawekar, and Mr. Pratik S. Jadhao. “MONKEYPOX VIRUS: AN OVERVIEW. Journal of Emerging Technologies and Innovative Research. 2021;8(6): 648-654.
  9. Jezek Z, Szczeniowski M, Paluku KM, Mutombo M. Human monkeypox: clinical features of 282 patients. J Infect Dis. 1987 Aug;156(2):293-8. doi: 10.1093/infdis/156.2.293. PMID: 3036967.
  10. Kumar N, Acharya A, Gendelman HE, Byrareddy SN. The 2022 outbreak and the pathobiology of the monkeypox virus. J Autoimmun. 2022 Jul;131:102855. doi: 10.1016/j.jaut.2022.102855. Epub 2022 Jun 25. PMID: 35760647; PMCID: PMC9534147.
  11. Kaler J, Hussain A, Flores G, Kheiri S, Desrosiers D. Monkeypox: A Comprehensive Review of Transmission, Pathogenesis, and Manifestation. Cureus. 2022 Jul 3;14(7):e26531. doi: 10.7759/cureus 26531. PMID: 35928395; PMCID: PMC9345383.
  12. Sberna G, Rozera G, Minosse C, Bordi L, Mazzotta V, D'Abramo A, Girardi E, Antinori A, Maggi F, Lalle E. Role of Direct Sexual Contact in Human Transmission of Monkeypox Virus, Italy. Emerg Infect Dis. 2024 Sep;30(9):1829-1833. doi: 10.3201/eid3009.240075. Epub 2024 Aug 10. PMID: 39127126; PMCID: PMC11346984.
  13. Ogoina D, Dalhat MM, Denue BA, Okowa M, Chika-Igwenyi NM, Oiwoh SO, Tobin EA, Yusuff HA, Ojimba AO, Christian UC, Aremu JT, Gomerep SS, Habila KL, Awang SK, Adekanmbi O, Iroezindu M, Onukak A, Falodun O, Sunday M, Johnson SM, Olaitan A, Onyeaghala C, Alasia D, Mmerem J, Unigwe U, Kwaghe V, Adeiza MA; Nigerian Infectious Diseases Society (NIDS) mpox study group. Mpox Epidemiology and Risk Factors, Nigeria, 2022. Emerg Infect Dis. 2024 Sep;30(9):1799-1808. doi: 10.3201/eid3009.240135. Epub 2024 Aug 10. PMID: 39127124; PMCID: PMC11346979.
  14. Iqbal T. MONKEY POX?A LOOMING HEALTH CRISIS FOR THE WORLD. Pak J Phsyiol [Internet]. 2022 Jun. 30 [cited 2024 Nov. 18];18(2):1-2.DOI: https://doi.org/10.69656/pjp.v18i2.1465
  15. Karagoz A, Tombuloglu H, Alsaeed M, Tombuloglu G, AlRubaish AA, Mahmoud A, Smajlović S, Ćordić S, Rabaan AA, Alsuhaimi E. Monkeypox (mpox) virus: Classification, origin, transmission, genome organization, antiviral drugs, and molecular diagnosis. J Infect Public Health. 2023 Apr;16(4):531-541. doi: 10.1016/j.jiph.2023.02.003. Epub 2023 Feb 9. PMID: 36801633; PMCID: PMC9908738.
  16. Dwivedi M, Gupta CLP, Tiwari RG. Comparative Result Analysis of Optimization Techniques in Convolutional Neural Network for Prediction and Diagnosis of Monkey Pox. 2023 Aug 5;2:1–6. doi: 10.1109/INDISCON58499.2023.10270750.
  17. Parker S, Nuara A, Buller RM, Schultz DA. Human monkeypox: an emerging zoonotic disease. Future Microbiol. 2007 Feb;2(1):17-34. doi: 10.2217/17460913.2.1.17. PMID: 17661673.
  18. Sompolwattana C. A Review on Epidemiology of Monkeypox and Prevention in Thailand. International Journal of Research Publications. 2022 Sep 1;109(1).doi :10.47119/ijrp1001091920223900
  19. Amiri F, Tabassum S, Melika Boroomand-Saboor, Laya Ohadi. Monkeypox and Recommendations for Cancer Patients. Mathews Journal of Emergency Medicine. 2023 Jan 1;8(1). doi:10.30654/mjem.10049
  20. Rizk, J.G., Lippi, G., Henry, B.M. et al. Prevention and Treatment of Monkeypox. Drugs 82, 957–963 (2022). https://doi.org/10.1007/s40265-022-01742-y
  21. Reynolds MG, McCollum AM, Nguete B, Shongo Lushima R, Petersen BW. Improving the Care and Treatment of Monkeypox Patients in Low-Resource Settings: Applying Evidence from Contemporary Biomedical and Smallpox Biodefense Research. Viruses. 2017 Dec 12;9(12):380. doi: 10.3390/v9120380. PMID: 29231870; PMCID: PMC5744154.
  22. PriyadharsiniRaman Palanisamy, Dhivya Elango, Vimala Ananthy, Subramanian U. Recent advances in the treatment of monkeypox drugs and vaccines. National Journal of Pharmacology and Therapeutics. 2023 Jan 1;1(2):65–5.DOI: 10.4103/njpt.njpt_18_23
  23. ‌Kugelman JR, Johnston SC, Mulembakani PM, Kisalu N, Lee MS, Koroleva G, McCarthy SE, Gestole MC, Wolfe ND, Fair JN, Schneider BS, Wright LL, Huggins J, Whitehouse CA, Wemakoy EO, Muyembe-Tamfum JJ, Hensley LE, Palacios GF, Rimoin AW. Genomic variability of monkeypox virus among humans, Democratic Republic of the Congo. Emerg Infect Dis. 2014 Feb;20(2):232-9. doi: 10.3201/eid2002.130118. PMID: 24457084; PMCID: PMC3901482.
  24. Ajmal A, Mahmood A, Hayat C, Hakami MA, Alotaibi BS, Umair M, Abdalla AN, Li P, He P, Wadood A, Hu J. Computer-assisted drug repurposing for thymidylate kinase drug target in monkeypox virus. Front Cell Infect Microbiol. 2023 May 29;13:1159389. doi: 10.3389/fcimb.2023.1159389. PMID: 37313340; PMCID: PMC10258308.
  25. Shen Y, Li Y, Yan R. Structural basis for the inhibition mechanism of the DNA polymerase holoenzyme from mpox virus. Structure. 2024 Jun 6;32(6):654-661.e3. doi: 10.1016/j.str.2024.03.004. Epub 2024 Apr 4. PMID: 38579705.
  26. Wang X, Ma L, Li N, Gao N. Structural insights into the assembly and mechanism of mpox virus DNA polymerase complex F8-A22-E4-H5. Mol Cell. 2023 Dec 7;83(23):4398-4412.e4. doi: 10.1016/j.molcel.2023.10.038. Epub 2023 Nov 22. PMID: 37995690.
  27. Li V, Lee Y, Lee C, Kim H. Repurposing existing drugs for monkeypox: applications of virtual screening methods. Genes Genomics. 2023 Nov;45(11):1347-1355. doi: 10.1007/s13258-023-01449-8. Epub 2023 Sep 15. PMID: 37713070; PMCID: PMC10587275.
  28. Hurle MR, Yang L, Xie Q, Rajpal DK, Sanseau P, Agarwal P. Computational drug repositioning: from data to therapeutics. Clin Pharmacol Ther. 2013 Apr;93(4):335-41. doi: 10.1038/clpt 2013.1. Epub 2013 Jan 15. PMID: 23443757.
  29. Hashemi M, Zabihian A, Hajsaeedi M, Hooshmand M. Antivirals for monkeypox virus: Proposing an effective machine/deep learning framework. PLoS One. 2024 Sep 12;19(9):e0299342. doi: 10.1371/journal.pon,e.0299342. PMID: 39264896.
  30. Alakunle E, Moens U, Nchinda G, Okeke MI. Monkeypox Virus in Nigeria: Infection Biology, Epidemiology, and Evolution. Viruses. 2020 Nov 5;12(11):1257. doi: 10.3390/v12111257. PMID: 33167496; PMCID: PMC7694534.
  31. da Silva GB, de Carvalho Braga G, Simões JLB, Kempka AP, Bagatini MD. Cytokine storm in human monkeypox: A possible involvement of purinergic signaling. Cytokine. 2024 May; 177:156560. doi: 10.1016/j.cyto.2024.156560. Epub 2024 Mar 5. PMID: 38447385.
  32. Anwar F, Haider F, Khan S, Ahmad I, Ahmed N, Imran M, Rashid S, Ren ZG, Khattak S, Ji XY. Clinical Manifestation, Transmission, Pathogenesis, and Diagnosis of Monkeypox Virus: A Comprehensive Review. Life (Basel). 2023 Feb 14;13(2):522. doi: 10.3390/life13020522. PMID: 36836879; PMCID: PMC9962527.
  33. Moss B. Poxvirus cell entry: how many proteins does it take? Viruses. 2012 May;4(5):688-707. doi: 10.3390/v4050688. Epub 2012 Apr 27. PMID: 22754644; PMCID: PMC3386626.
  34. Schmidt FI, Bleck CK, Mercer J. Poxvirus host cell entry. Curr Opin Virol. 2012 Feb;2(1):20-7. doi: 10.1016/j.coviro.2011.11.007. Epub 2011 Dec 27. PMID: 22440962.
  35. 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 Mar 3;7:42717. doi: 10.1038/srep42717. PMID: 28256516; PMCID: PMC5335600.
  36. Ali SMA, Helina N, Kumar SV, Varshini E, Ahmad KMFT, Rajamohamed H. Novel Drug Repurposing Strategy as an Alternative Therapeutic Concept for Scrub Typhus Using Computational Studies.  J Pure Appl Microbiol. 2024;18(2):1167-1176. doi: 10.22207/JPAM.18.2.35.
  37. 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 7, 42717 (2017). https://doi.org/10.1038/srep42717.
  38. Gulati P, Chadha J, Harjai K, Singh S. Targeting envelope proteins of poxviruses to repurpose phytochemicals against monkeypox: An in silico investigation. Front Microbiol. 2023 Jan 5;13:1073419. doi: 10.3389/fmicb.2022.1073419. PMID: 36687601; PMCID: PMC9849581.
  39. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001 Mar 1;46(1-3):3-26. doi: 10.1016/s0169-409x(00)00129-0. PMID: 11259830.

Monkeypox viral infection is emerging as a significant threat and concern worldwide for the human population. Still, the available treatment options don’t meet the requirement, increasing the mortality and morbidity. This fosters the researchers to engage in the development of novel treatment strategies or drug repurposing to overcome the hurdle. With this background, the identification of potential drug targets can significantly amplify the development of potent drug molecules for the treatment. The proteins responsible for viral replication should be targeted, and hindering these proteins should be the key findings to reduce the morbidity and mortality. The literature review provides insight into two viral proteins, viral core Thymidylate Kinase (2V54) and DNA polymerase holoenzyme (8HG1), which are primarily responsible for disease aggravation. Sixty-four antiviral agents approved by the FDA were selected and evaluated against both viral proteins via simulation screening. These antiviral agents possess the capability to obstruct bacterial protein production, rendering them significant candidates for medication repurposing. According to the screening outcomes against DNA polymerase holoenzyme, the two leading compounds, Dolutegravir and Raltegravir, with docking values of – 10.0 and –9.7 kcal/mol, respectively, were chosen for further examination. Raltegravir and Etavirine, exhibiting docking scores of −10.0 and −9.6 kcal/mol, respectively, against thymidine kinase are the leading compounds identified following the validation of the protease with the pharmacological library. While investigating medications targeting proteinase, the top two molecules, Dolutegravir and Raltegravir, had the highest docking scores. These two medicinal compounds have significant inhibitory capabilities against MPXV proteinase Thymidine kinase and DNA polymerase protein. Ultimately, the current research illustrates the repurposing of antiviral medicines as a treatment for monkeypox viral infection.

Keywords : Monkeypox Virus, Thymidylate Kinase, DNA Polymerase Holoenzyme, Antiviral Agents.

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