In silico Evaluation of the Potential of Natural Products from Chili Pepper as Antiviral Agents Against Dna-Directed Rna Polymerase of the Monkeypox Virus
Yıl 2024,
, 277 - 291, 24.03.2024
Özkan Fidan
Somdutt Mujwar
Öz
This study focused on the discovery of new drug candidates effective against the monkeypox virus. Virtual screening was performed to evaluate the potential of chili pepper natural products against homology-modeled DNA-directed RNA polymerase of the monkeypox virus using molecular docking. Our findings revealed that structurally similar triterpenes such as α-amyrin, β-amyrin, and β-sitosterol had strong binding affinities towards the DNA-directed RNA polymerase and can inhibit this pivotal viral enzyme. The stability of one of the drug candidate molecules, α-amyrin with the strongest binding affinity towards the binding cavity of the enzyme was also confirmed via molecular dynamics simulation. This study showed that α-amyrin is a promising DNA-directed RNA polymerase inhibitor to treat monkeypox disease. It also paves the way for the idea of the potential dietary supplement candidate for monkeypox patients.
Kaynakça
- [1] S. Riedel, “Edward Jenner and the history of smallpox and vaccination,” Proc. (Bayl. Univ. Med. Cent)., vol. 18, no. 1, p. 21, Jan. 2005, doi: 10.1080/08998280.2005.11928028.
- [2] J. Guarner, C. del Rio, and P. N. Malani, “Monkeypox in 2022—What Clinicians Need to Know,” JAMA, vol. 328, no. 2, pp. 139–140, Jul. 2022, doi: 10.1001/JAMA.2022.10802.
- [3] S. R. Chowdhury, P. K. Datta, and S. Maitra, “Monkeypox and its pandemic potential: what the anaesthetist should know,” Br. J. Anaesth., vol. 0, no. 0, Jul. 2022, doi: 10.1016/J.BJA.2022.06.007.
- [4] E. M. Bunge et al., “The changing epidemiology of human monkeypox—A potential threat? A systematic review,” PLoS Negl. Trop. Dis., vol. 16, no. 2, p. e0010141, Feb. 2022, doi: 10.1371/JOURNAL.PNTD.0010141.
- [5] Z. Ježek, M. Szczeniowski, K. M. Paluku, and M. Mutombo, “Human monkeypox: clinical features of 282 patients,” J Infect Dis, vol. 156, pp. 293–298, 1987.
- [6] A. L. Hughes, S. Irausquin, and R. Friedman, “The evolutionary biology of poxviruses,” Infect. Genet. Evol., vol. 10, no. 1, pp. 50–59, Jan. 2010, doi: 10.1016/J.MEEGID.2009.10.001.
- [7] S. N. Shchelkunov et al., “Human monkeypox and smallpox viruses: genomic comparison,” FEBS Lett., vol. 509, no. 1, pp. 66–70, Nov. 2001, doi: 10.1016/S0014-5793(01)03144-1.
- [8] C. T. Cho and H. A. Wenner, “Monkeypox Virus,” Bacteriol. Rev., vol. 37, no. 1, pp. 1–13, 1973, Accessed: Jul. 20, 2022. [Online]. Available: https://journals.asm.org/journal/br
- [9] F. S. Minhaj et al., “Monkeypox Outbreak — Nine States, May 2022,” Morb. Mortal. Wkly. Rep., vol. 71, no. 23, p. 764, Jun. 2022, doi: 10.15585/MMWR.MM7123E1.
- [10] D. Mileto et al., “New challenges in human monkeypox outside Africa: A review and case report from Italy,” Travel Med. Infect. Dis., vol. 49, p. 102386, Sep. 2022, doi: 10.1016/J.TMAID.2022.102386.
- [11] A. Zumla et al., “Monkeypox outbreaks outside endemic regions: scientific and social priorities,” Lancet. Infect. Dis., vol. 22, no. 7, p. 929, Jul. 2022, doi: 10.1016/S1473-3099(22)00354-1.
- [12] D. W. Grosenbach et al., “Oral Tecovirimat for the Treatment of Smallpox,” N. Engl. J. Med., vol. 379, no. 1, pp. 44–53, Jul. 2018, doi: 10.1056/NEJMOA1705688.
- [13] G. Chittick, M. Morrison, T. Brundage, and W. G. Nichols, “Short-term clinical safety profile of brincidofovir: A favorable benefit–risk proposition in the treatment of smallpox,” Antiviral Res., vol. 143, pp. 269–277, Jul. 2017, doi: 10.1016/j.antiviral.2017.01.009.
- [14] C. L. Hutson et al., “Pharmacokinetics and efficacy of a potential smallpox therapeutic, brincidofovir, in a lethal monkeypox virus animal model,” Am Soc Microbiol, vol. 6, no. 1, Feb. 2022, doi: 10.1128/mSphere.00927-20.
- [15] A. T. Russo et al., “Effects of treatment delay on efficacy of tecovirimat following lethal aerosol monkeypox virus challenge in cynomolgus macaques,” J. Infect. Dis., vol. 218, no. 9, pp. 1490–1499, Sep. 2018, doi: 10.1093/INFDIS/JIY326.
- [16] H. Adler et al., “Clinical features and management of human monkeypox: a retrospective observational study in the UK,” Lancet Infect. Dis., vol. 22, no. 8, pp. 1153–1162, Aug. 2022, doi: 10.1016/S1473-3099(22)00228-6.
- [17] J. G. Rizk, G. Lippi, B. M. Henry, D. N. Forthal, and Y. Rizk, “Prevention and Treatment of Monkeypox.,” Drugs, vol. 82, no. 9, pp. 957–963, Jun. 2022, doi: 10.1007/S40265-022-01742-Y.
- [18] A. M. Vera-Guzmán, E. N. Aquino-Bolaños, E. Heredia-García, J. C. Carrillo-Rodríguez, S. Hernández-Delgado, and J. L. Chávez-Servia, “Flavonoid and Capsaicinoid Contents and Consumption of Mexican Chili Pepper (Capsicum annuum L.) Landraces,” Flavonoids - From Biosynth. to Hum. Heal., Aug. 2017, doi: 10.5772/68076.
- [19] A. Wesołowska, D. J.-A. S. Pol., U. Hortorum, and U. 2011, “Chemical composition of the pepper fruit extracts of hot cultivars Capsicum annuum L,” Acta Sci. Pol., Hortorum Cultus, vol. 10, no. 1, pp. 171–184, 2011, Accessed: Jul.
26, 2022. [Online]. Available: https://czasopisma.up.lublin.pl/index.php/asphc/article/view/3190.
- [20] S. E. Altmann et al., “Inhibition of cowpox virus and monkeypox virus infection by mitoxantrone,” Antiviral Res., vol. 93, no. 2, pp. 305–308, Feb. 2012, doi: 10.1016/J.ANTIVIRAL.2011.12.001.
- [21] J. Deval, J. A. Symons, and L. Beigelman, “Inhibition of viral RNA polymerases by nucleoside and nucleotide analogs: therapeutic applications against positive-strand RNA viruses beyond hepatitis C virus,” Curr. Opin. Virol., vol. 9, p. 1, 2014, doi: 10.1016/J.COVIRO.2014.08.004.
- [22] S. Mujwar, L. Sun, and O. Fidan, “In silico evaluation of food-derived carotenoids against SARS-CoV-2 drug targets: Crocin is a promising dietary supplement candidate for COVID-19,” J. Food Biochem., p. e14219, 2022, doi: 10.1111/JFBC.14219.
- [23] Y. Furuta, B. B. Gowen, K. Takahashi, K. Shiraki, D. F. Smee, and D. L. Barnard, “Favipiravir (T-705), a novel viral RNA polymerase inhibitor,” Antiviral Res., vol. 100, no. 2, pp. 446–454, Nov. 2013, doi: 10.1016/J.ANTIVIRAL.2013.09.015.
- [24] N. Rahmattullah, E. Laras Arumingtyas, M. Hermawan Widyananda, A. N. Ahyar, and I. Tabroni, “Bioinformatics Analysis of Bioactive Compounds of Four Capsicum Species against SARS-CoV-2 Infection,” Int. J. Adv. Biol. Biomed. Res., vol. 9, no. 4, pp. 298–319, 2021, doi: 10.22034/ijabbr.2021.139183.1335.
- [25] N. Ordaz-Trinidad, L. Dorantes-Álvarez, J. Salas-Benito, B. L. Barrón-Romero, M. Salas-Benito, and M. De Nova-Ocampo, “Cytotoxicity and antiviral activity of pepper extracts (Capsicum spp),” Polibotánica, vol. 0, no. 46, Jul. 2018, doi: 10.18387/POLIBOTANICA.46.18.
- [26] K. Tang, X. Zhang, and Y. Guo, “Identification of the dietary supplement capsaicin as an inhibitor of Lassa virus entry,” Acta Pharm. Sin. B, vol. 10, no. 5, pp. 789–798, May 2020, doi: 10.1016/J.APSB.2020.02.014.
- [27] T. A. Hafiz, M. A. Mubaraki, M. A. Dkhil, and S. Al-Quraishy, “Antiviral Activities of Capsicum annuum Methanolic Extract against Herpes Simplex Virus 1 and 2,” Pak. J. Zool., vol. 49, no. 1, pp. 251–255, Jan. 2017, doi: 10.17582/JOURNAL.PJZ/2017.49.1.251.255.
- [28] K. H. Choi, “Viral polymerases,” Adv. Exp. Med. Biol., vol. 726, pp. 267–304, 2012, doi: 10.1007/978-1-4614-0980-9_12/COVER.
- [29] A. Bateman et al., “UniProt: the universal protein knowledgebase in 2021,” Nucleic Acids Res., vol. 49, no. D1, p. D480, Jan. 2021, doi: 10.1093/NAR/GKAA1100.
- [30] W. D. Arndt et al., “Monkeypox virus induces the synthesis of less dsRNA than vaccinia virus, and is more resistant to the anti-poxvirus drug, IBT, than vaccinia virus,” Virology, vol. 497, pp. 125–135, Oct. 2016, doi: 10.1016/J.VIROL.2016.07.016.
- [31] A. Waterhouse et al., “SWISS-MODEL: homology modelling of protein structures and complexes,” Nucleic Acids Res., vol. 46, no. W1, pp. W296–W303, Jul. 2018, doi: 10.1093/NAR/GKY427.
- [32] K. Gopalakrishnan, G. Sowmiya, S. S. Sheik, and K. Sekar, “Ramachandran Plot on The Web (2.0),” Protein Pept. Lett., vol. 14, no. 7, pp. 669–671, Aug. 2007, doi: 10.2174/092986607781483912.
- [33] S. Mujwar and R. K. Harwansh, “In silico bioprospecting of taraxerol as a main protease inhibitor of SARS-CoV-2 to develop therapy against COVID-19,” Struct. Chem., vol. 1, p. 1, 2022, doi: 10.1007/S11224-022-01943-X.
- [34] O. Fidan, S. Mujwar, and M. Kciuk, “Discovery of adapalene and dihydrotachysterol as antiviral agents for the Omicron variant of SARS-CoV-2 through computational drug repurposing,” Mol. Divers., vol. 27, no. 1, pp. 463–475, Feb. 2023, doi: 10.1007/S11030-022-10440-6.
- [35] S. Mujwar, K. Shah, J. K. Gupta, and A. Gour, “Docking based screening of curcumin derivatives: A novel approach in the inhibition of tubercular DHFR,” Int. J. Comput. Biol. Drug Des., vol. 14, no. 4, pp. 297–314, 2021, doi: 10.1504/IJCBDD.2021.118830.
- [36] S. Mujwar, “Computational bioprospecting of andrographolide derivatives as potent cyclooxygenase-2 inhibitors,” Biomed. Biotechnol. Res. J., vol. 5, no. 4, p. 446, Oct. 2021, doi: 10.4103/BBRJ.BBRJ_56_21.
- [37] D. E. V. Pires, T. L. Blundell, and D. B. Ascher, “pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures,” J. Med. Chem., vol. 58, no. 9, pp. 4066–4072, May 2015, doi: 10.1021/ACS.JMEDCHEM.5B00104.
- [38] R. Jain and S. Mujwar, “Repurposing metocurine as main protease inhibitor to develop novel antiviral therapy for COVID-19,” Struct. Chem., pp. 1–13, 2020, doi: https://doi.org/10.1007/s11224-020-01605-w.
- [39] S. Mujwar, “Computational repurposing of tamibarotene against triple mutant variant of SARS-CoV-2,” Comput Biol Med, vol. 136, p. 104748, 2021, doi: https://doi.org/10.1016/j.compbiomed.2021.104748.
- [40] K. Shah, S. Mujwar, G. Krishna, and J. K. Gupta, “Computational Design and Biological Depiction of Novel Naproxen Derivative,” https://home.liebertpub.com/adt, vol. 18, no. 7, pp. 308–317, Oct. 2020, doi: 10.1089/ADT.2020.977.
- [41] H. S. Hillen et al., “Structural Basis of Poxvirus Transcription: Transcribing and Capping Vaccinia Complexes,” Cell, vol. 179, no. 7, pp. 1525-1536.e12, Dec. 2019, doi: 10.1016/J.CELL.2019.11.023.
- [42] C. Grimm, J. Bartuli, B. Boettcher, A. A. Szalay, and U. Fischer, “Structural basis of the complete poxvirus transcription initiation process,” Nat. Struct. Mol. Biol. 2021 2810, vol. 28, no. 10, pp. 779–788, Sep. 2021, doi: 10.1038/s41594-021-00655-w.
- [43] L. Z. Benet, C. M. Hosey, O. Ursu, and T. I. Oprea, “BDDCS, the Rule of 5 and drugability,” Adv. Drug Deliv. Rev., vol. 101, pp. 89–98, Jun. 2016, doi: 10.1016/J.ADDR.2016.05.007.
- [44] B. L. Ligon, “Monkeypox: A review of the history and emergence in the Western hemisphere,” Semin. Pediatr. Infect. Dis., vol. 15, no. 4, pp. 280–287, Oct. 2004, doi: 10.1053/J.SPID.2004.09.001.
- [45] J. S. Bryer, E. E. Freeman, and M. Rosenbach, “Monkeypox emerges on a global scale: a historical review and dermatological primer,” J. Am. Acad. Dermatol., Jul. 2022, doi: 10.1016/J.JAAD.2022.07.007.
- [46] J. P. Thornhill et al., “Monkeypox Virus Infection in Humans across 16 Countries - April-June 2022.,” N. Engl. J. Med., Jul. 2022, doi: 10.1056/NEJMOA2207323.
- [47] B. K. Saleh, “Medicinal uses and health benefits of chili pepper (Capsicum spp.): a review Evaluation of husbandry, insect pest, diseases and management practices of vegetables cultivated in Zoba Anseba Eritrea View project Mycology isolation of fungi from sorghum pearl millet View project,” 2018, doi:
10.15406/mojfpt.2018.06.00183.
- [48] S. Idrees, M. A. Hanif, M. A. Ayub, A. Hanif, and T. M. Ansari, “Chili Pepper,” Med. Plants South Asia Nov. Sources Drug Discov., pp. 113–124, Jan. 2020, doi: 10.1016/B978-0-08-102659-5.00009-4.
- [49] G. E. S. Batiha et al., “Biological Properties, Bioactive Constituents, and Pharmacokinetics of Some Capsicum spp. and Capsaicinoids,” Int. J. Mol. Sci., vol. 21, no. 15, pp. 1–35, Aug. 2020, doi: 10.3390/IJMS21155179.
- [50] K. Srinivasan, “Biological Activities of Red Pepper (Capsicum annuum) and Its Pungent Principle Capsaicin: A Review,” http://dx.doi.org/10.1080/10408398.2013.772090, vol. 56, no. 9, pp. 1488–1500, Jul. 2015, doi: 10.1080/10408398.2013.772090.
- [51] T. A. Alandijany et al., “A multi-targeted computational drug discovery approach for repurposing tetracyclines against monkeypox virus,” Sci. Reports 2023 131, vol. 13, no. 1, pp. 1–22, Sep. 2023, doi: 10.1038/s41598-023-41820-z.
- [52] S. Akash et al., “Anti-viral drug discovery against monkeypox and smallpox infection by natural curcumin derivatives: A Computational drug design approach,” Front. Cell. Infect. Microbiol., vol. 13, p. 1157627, 2023, doi: 10.3389/FCIMB.2023.1157627.
- [53] A. O. Nogueira, Y. I. S. Oliveira, B. L. Adjafre, M. E. A. de Moraes, and G. F. Aragão, “Pharmacological effects of the isomeric mixture of alpha and beta amyrin from Protium heptaphyllum: a literature review,” Fundam. Clin. Pharmacol., vol. 33, no. 1, pp. 4–12, Feb. 2019, doi: 10.1111/FCP.12402.
- [54] F. A. Santos et al., “Antihyperglycemic and hypolipidemic effects of α,β-amyrin, a triterpenoid mixture from Protium heptaphyllum in mice,” Lipids Health Dis., vol. 11, no. 1, pp. 1–8, Aug. 2012, doi: 10.1186/1476-511X-11-98.
- [55] G. F. Aragao, M. C. C. Pinheiro, P. N. Bandeira, T. L. G. Lemos, and G. S. de B. Viana, “Analgesic and Anti-Inflammatory Activities of the Isomeric Mixture of Alpha- and Beta-Amyrin from Protium heptaphyllum(Aubl.) March,” http://dx.doi.org/10.1080/J157v07n02_03, vol. 7, no. 2, pp. 31–47, Jan. 2009, doi: 10.1080/J157V07N02_03.
- [56] L. Fraile, E. Crisci, L. Córdoba, M. A. Navarro, J. Osada, and M. Montoya, “Immunomodulatory properties of Beta-sitosterol in pig immune responses,” Int. Immunopharmacol., vol. 13, no. 3, pp. 316–321, Jul. 2012, doi: 10.1016/J.INTIMP.2012.04.017.
- [57] R. Pompei, O. Flore, M. A. Marccialis, A. Pani, and B. Loddo, “Glycyrrhizic acid inhibits virus growth and inactivates virus particles,” Nat. 1979 2815733, vol. 281, no. 5733, pp. 689–690, 1979, doi: 10.1038/281689a0.
- [58] V. K. Maurya, S. Kumar, M. L. B. Bhatt, and S. K. Saxena, “Antiviral activity of traditional medicinal plants from Ayurveda against SARS-CoV-2 infection,” J. Biomol. Struct. Dyn., vol. 40, no. 4, pp. 1719–1735, 2022, doi: 10.1080/07391102.2020.1832577.
- [59] B. Kar, B. Dehury, M. K. Singh, S. Pati, and D. Bhattacharya, “Identification of phytocompounds as newer antiviral drugs against COVID-19 through molecular docking and simulation based study,” J. Mol. Graph. Model., vol. 114, p. 108192, Jul. 2022, doi: 10.1016/J.JMGM.2022.108192.
Yıl 2024,
, 277 - 291, 24.03.2024
Özkan Fidan
Somdutt Mujwar
Kaynakça
- [1] S. Riedel, “Edward Jenner and the history of smallpox and vaccination,” Proc. (Bayl. Univ. Med. Cent)., vol. 18, no. 1, p. 21, Jan. 2005, doi: 10.1080/08998280.2005.11928028.
- [2] J. Guarner, C. del Rio, and P. N. Malani, “Monkeypox in 2022—What Clinicians Need to Know,” JAMA, vol. 328, no. 2, pp. 139–140, Jul. 2022, doi: 10.1001/JAMA.2022.10802.
- [3] S. R. Chowdhury, P. K. Datta, and S. Maitra, “Monkeypox and its pandemic potential: what the anaesthetist should know,” Br. J. Anaesth., vol. 0, no. 0, Jul. 2022, doi: 10.1016/J.BJA.2022.06.007.
- [4] E. M. Bunge et al., “The changing epidemiology of human monkeypox—A potential threat? A systematic review,” PLoS Negl. Trop. Dis., vol. 16, no. 2, p. e0010141, Feb. 2022, doi: 10.1371/JOURNAL.PNTD.0010141.
- [5] Z. Ježek, M. Szczeniowski, K. M. Paluku, and M. Mutombo, “Human monkeypox: clinical features of 282 patients,” J Infect Dis, vol. 156, pp. 293–298, 1987.
- [6] A. L. Hughes, S. Irausquin, and R. Friedman, “The evolutionary biology of poxviruses,” Infect. Genet. Evol., vol. 10, no. 1, pp. 50–59, Jan. 2010, doi: 10.1016/J.MEEGID.2009.10.001.
- [7] S. N. Shchelkunov et al., “Human monkeypox and smallpox viruses: genomic comparison,” FEBS Lett., vol. 509, no. 1, pp. 66–70, Nov. 2001, doi: 10.1016/S0014-5793(01)03144-1.
- [8] C. T. Cho and H. A. Wenner, “Monkeypox Virus,” Bacteriol. Rev., vol. 37, no. 1, pp. 1–13, 1973, Accessed: Jul. 20, 2022. [Online]. Available: https://journals.asm.org/journal/br
- [9] F. S. Minhaj et al., “Monkeypox Outbreak — Nine States, May 2022,” Morb. Mortal. Wkly. Rep., vol. 71, no. 23, p. 764, Jun. 2022, doi: 10.15585/MMWR.MM7123E1.
- [10] D. Mileto et al., “New challenges in human monkeypox outside Africa: A review and case report from Italy,” Travel Med. Infect. Dis., vol. 49, p. 102386, Sep. 2022, doi: 10.1016/J.TMAID.2022.102386.
- [11] A. Zumla et al., “Monkeypox outbreaks outside endemic regions: scientific and social priorities,” Lancet. Infect. Dis., vol. 22, no. 7, p. 929, Jul. 2022, doi: 10.1016/S1473-3099(22)00354-1.
- [12] D. W. Grosenbach et al., “Oral Tecovirimat for the Treatment of Smallpox,” N. Engl. J. Med., vol. 379, no. 1, pp. 44–53, Jul. 2018, doi: 10.1056/NEJMOA1705688.
- [13] G. Chittick, M. Morrison, T. Brundage, and W. G. Nichols, “Short-term clinical safety profile of brincidofovir: A favorable benefit–risk proposition in the treatment of smallpox,” Antiviral Res., vol. 143, pp. 269–277, Jul. 2017, doi: 10.1016/j.antiviral.2017.01.009.
- [14] C. L. Hutson et al., “Pharmacokinetics and efficacy of a potential smallpox therapeutic, brincidofovir, in a lethal monkeypox virus animal model,” Am Soc Microbiol, vol. 6, no. 1, Feb. 2022, doi: 10.1128/mSphere.00927-20.
- [15] A. T. Russo et al., “Effects of treatment delay on efficacy of tecovirimat following lethal aerosol monkeypox virus challenge in cynomolgus macaques,” J. Infect. Dis., vol. 218, no. 9, pp. 1490–1499, Sep. 2018, doi: 10.1093/INFDIS/JIY326.
- [16] H. Adler et al., “Clinical features and management of human monkeypox: a retrospective observational study in the UK,” Lancet Infect. Dis., vol. 22, no. 8, pp. 1153–1162, Aug. 2022, doi: 10.1016/S1473-3099(22)00228-6.
- [17] J. G. Rizk, G. Lippi, B. M. Henry, D. N. Forthal, and Y. Rizk, “Prevention and Treatment of Monkeypox.,” Drugs, vol. 82, no. 9, pp. 957–963, Jun. 2022, doi: 10.1007/S40265-022-01742-Y.
- [18] A. M. Vera-Guzmán, E. N. Aquino-Bolaños, E. Heredia-García, J. C. Carrillo-Rodríguez, S. Hernández-Delgado, and J. L. Chávez-Servia, “Flavonoid and Capsaicinoid Contents and Consumption of Mexican Chili Pepper (Capsicum annuum L.) Landraces,” Flavonoids - From Biosynth. to Hum. Heal., Aug. 2017, doi: 10.5772/68076.
- [19] A. Wesołowska, D. J.-A. S. Pol., U. Hortorum, and U. 2011, “Chemical composition of the pepper fruit extracts of hot cultivars Capsicum annuum L,” Acta Sci. Pol., Hortorum Cultus, vol. 10, no. 1, pp. 171–184, 2011, Accessed: Jul.
26, 2022. [Online]. Available: https://czasopisma.up.lublin.pl/index.php/asphc/article/view/3190.
- [20] S. E. Altmann et al., “Inhibition of cowpox virus and monkeypox virus infection by mitoxantrone,” Antiviral Res., vol. 93, no. 2, pp. 305–308, Feb. 2012, doi: 10.1016/J.ANTIVIRAL.2011.12.001.
- [21] J. Deval, J. A. Symons, and L. Beigelman, “Inhibition of viral RNA polymerases by nucleoside and nucleotide analogs: therapeutic applications against positive-strand RNA viruses beyond hepatitis C virus,” Curr. Opin. Virol., vol. 9, p. 1, 2014, doi: 10.1016/J.COVIRO.2014.08.004.
- [22] S. Mujwar, L. Sun, and O. Fidan, “In silico evaluation of food-derived carotenoids against SARS-CoV-2 drug targets: Crocin is a promising dietary supplement candidate for COVID-19,” J. Food Biochem., p. e14219, 2022, doi: 10.1111/JFBC.14219.
- [23] Y. Furuta, B. B. Gowen, K. Takahashi, K. Shiraki, D. F. Smee, and D. L. Barnard, “Favipiravir (T-705), a novel viral RNA polymerase inhibitor,” Antiviral Res., vol. 100, no. 2, pp. 446–454, Nov. 2013, doi: 10.1016/J.ANTIVIRAL.2013.09.015.
- [24] N. Rahmattullah, E. Laras Arumingtyas, M. Hermawan Widyananda, A. N. Ahyar, and I. Tabroni, “Bioinformatics Analysis of Bioactive Compounds of Four Capsicum Species against SARS-CoV-2 Infection,” Int. J. Adv. Biol. Biomed. Res., vol. 9, no. 4, pp. 298–319, 2021, doi: 10.22034/ijabbr.2021.139183.1335.
- [25] N. Ordaz-Trinidad, L. Dorantes-Álvarez, J. Salas-Benito, B. L. Barrón-Romero, M. Salas-Benito, and M. De Nova-Ocampo, “Cytotoxicity and antiviral activity of pepper extracts (Capsicum spp),” Polibotánica, vol. 0, no. 46, Jul. 2018, doi: 10.18387/POLIBOTANICA.46.18.
- [26] K. Tang, X. Zhang, and Y. Guo, “Identification of the dietary supplement capsaicin as an inhibitor of Lassa virus entry,” Acta Pharm. Sin. B, vol. 10, no. 5, pp. 789–798, May 2020, doi: 10.1016/J.APSB.2020.02.014.
- [27] T. A. Hafiz, M. A. Mubaraki, M. A. Dkhil, and S. Al-Quraishy, “Antiviral Activities of Capsicum annuum Methanolic Extract against Herpes Simplex Virus 1 and 2,” Pak. J. Zool., vol. 49, no. 1, pp. 251–255, Jan. 2017, doi: 10.17582/JOURNAL.PJZ/2017.49.1.251.255.
- [28] K. H. Choi, “Viral polymerases,” Adv. Exp. Med. Biol., vol. 726, pp. 267–304, 2012, doi: 10.1007/978-1-4614-0980-9_12/COVER.
- [29] A. Bateman et al., “UniProt: the universal protein knowledgebase in 2021,” Nucleic Acids Res., vol. 49, no. D1, p. D480, Jan. 2021, doi: 10.1093/NAR/GKAA1100.
- [30] W. D. Arndt et al., “Monkeypox virus induces the synthesis of less dsRNA than vaccinia virus, and is more resistant to the anti-poxvirus drug, IBT, than vaccinia virus,” Virology, vol. 497, pp. 125–135, Oct. 2016, doi: 10.1016/J.VIROL.2016.07.016.
- [31] A. Waterhouse et al., “SWISS-MODEL: homology modelling of protein structures and complexes,” Nucleic Acids Res., vol. 46, no. W1, pp. W296–W303, Jul. 2018, doi: 10.1093/NAR/GKY427.
- [32] K. Gopalakrishnan, G. Sowmiya, S. S. Sheik, and K. Sekar, “Ramachandran Plot on The Web (2.0),” Protein Pept. Lett., vol. 14, no. 7, pp. 669–671, Aug. 2007, doi: 10.2174/092986607781483912.
- [33] S. Mujwar and R. K. Harwansh, “In silico bioprospecting of taraxerol as a main protease inhibitor of SARS-CoV-2 to develop therapy against COVID-19,” Struct. Chem., vol. 1, p. 1, 2022, doi: 10.1007/S11224-022-01943-X.
- [34] O. Fidan, S. Mujwar, and M. Kciuk, “Discovery of adapalene and dihydrotachysterol as antiviral agents for the Omicron variant of SARS-CoV-2 through computational drug repurposing,” Mol. Divers., vol. 27, no. 1, pp. 463–475, Feb. 2023, doi: 10.1007/S11030-022-10440-6.
- [35] S. Mujwar, K. Shah, J. K. Gupta, and A. Gour, “Docking based screening of curcumin derivatives: A novel approach in the inhibition of tubercular DHFR,” Int. J. Comput. Biol. Drug Des., vol. 14, no. 4, pp. 297–314, 2021, doi: 10.1504/IJCBDD.2021.118830.
- [36] S. Mujwar, “Computational bioprospecting of andrographolide derivatives as potent cyclooxygenase-2 inhibitors,” Biomed. Biotechnol. Res. J., vol. 5, no. 4, p. 446, Oct. 2021, doi: 10.4103/BBRJ.BBRJ_56_21.
- [37] D. E. V. Pires, T. L. Blundell, and D. B. Ascher, “pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures,” J. Med. Chem., vol. 58, no. 9, pp. 4066–4072, May 2015, doi: 10.1021/ACS.JMEDCHEM.5B00104.
- [38] R. Jain and S. Mujwar, “Repurposing metocurine as main protease inhibitor to develop novel antiviral therapy for COVID-19,” Struct. Chem., pp. 1–13, 2020, doi: https://doi.org/10.1007/s11224-020-01605-w.
- [39] S. Mujwar, “Computational repurposing of tamibarotene against triple mutant variant of SARS-CoV-2,” Comput Biol Med, vol. 136, p. 104748, 2021, doi: https://doi.org/10.1016/j.compbiomed.2021.104748.
- [40] K. Shah, S. Mujwar, G. Krishna, and J. K. Gupta, “Computational Design and Biological Depiction of Novel Naproxen Derivative,” https://home.liebertpub.com/adt, vol. 18, no. 7, pp. 308–317, Oct. 2020, doi: 10.1089/ADT.2020.977.
- [41] H. S. Hillen et al., “Structural Basis of Poxvirus Transcription: Transcribing and Capping Vaccinia Complexes,” Cell, vol. 179, no. 7, pp. 1525-1536.e12, Dec. 2019, doi: 10.1016/J.CELL.2019.11.023.
- [42] C. Grimm, J. Bartuli, B. Boettcher, A. A. Szalay, and U. Fischer, “Structural basis of the complete poxvirus transcription initiation process,” Nat. Struct. Mol. Biol. 2021 2810, vol. 28, no. 10, pp. 779–788, Sep. 2021, doi: 10.1038/s41594-021-00655-w.
- [43] L. Z. Benet, C. M. Hosey, O. Ursu, and T. I. Oprea, “BDDCS, the Rule of 5 and drugability,” Adv. Drug Deliv. Rev., vol. 101, pp. 89–98, Jun. 2016, doi: 10.1016/J.ADDR.2016.05.007.
- [44] B. L. Ligon, “Monkeypox: A review of the history and emergence in the Western hemisphere,” Semin. Pediatr. Infect. Dis., vol. 15, no. 4, pp. 280–287, Oct. 2004, doi: 10.1053/J.SPID.2004.09.001.
- [45] J. S. Bryer, E. E. Freeman, and M. Rosenbach, “Monkeypox emerges on a global scale: a historical review and dermatological primer,” J. Am. Acad. Dermatol., Jul. 2022, doi: 10.1016/J.JAAD.2022.07.007.
- [46] J. P. Thornhill et al., “Monkeypox Virus Infection in Humans across 16 Countries - April-June 2022.,” N. Engl. J. Med., Jul. 2022, doi: 10.1056/NEJMOA2207323.
- [47] B. K. Saleh, “Medicinal uses and health benefits of chili pepper (Capsicum spp.): a review Evaluation of husbandry, insect pest, diseases and management practices of vegetables cultivated in Zoba Anseba Eritrea View project Mycology isolation of fungi from sorghum pearl millet View project,” 2018, doi:
10.15406/mojfpt.2018.06.00183.
- [48] S. Idrees, M. A. Hanif, M. A. Ayub, A. Hanif, and T. M. Ansari, “Chili Pepper,” Med. Plants South Asia Nov. Sources Drug Discov., pp. 113–124, Jan. 2020, doi: 10.1016/B978-0-08-102659-5.00009-4.
- [49] G. E. S. Batiha et al., “Biological Properties, Bioactive Constituents, and Pharmacokinetics of Some Capsicum spp. and Capsaicinoids,” Int. J. Mol. Sci., vol. 21, no. 15, pp. 1–35, Aug. 2020, doi: 10.3390/IJMS21155179.
- [50] K. Srinivasan, “Biological Activities of Red Pepper (Capsicum annuum) and Its Pungent Principle Capsaicin: A Review,” http://dx.doi.org/10.1080/10408398.2013.772090, vol. 56, no. 9, pp. 1488–1500, Jul. 2015, doi: 10.1080/10408398.2013.772090.
- [51] T. A. Alandijany et al., “A multi-targeted computational drug discovery approach for repurposing tetracyclines against monkeypox virus,” Sci. Reports 2023 131, vol. 13, no. 1, pp. 1–22, Sep. 2023, doi: 10.1038/s41598-023-41820-z.
- [52] S. Akash et al., “Anti-viral drug discovery against monkeypox and smallpox infection by natural curcumin derivatives: A Computational drug design approach,” Front. Cell. Infect. Microbiol., vol. 13, p. 1157627, 2023, doi: 10.3389/FCIMB.2023.1157627.
- [53] A. O. Nogueira, Y. I. S. Oliveira, B. L. Adjafre, M. E. A. de Moraes, and G. F. Aragão, “Pharmacological effects of the isomeric mixture of alpha and beta amyrin from Protium heptaphyllum: a literature review,” Fundam. Clin. Pharmacol., vol. 33, no. 1, pp. 4–12, Feb. 2019, doi: 10.1111/FCP.12402.
- [54] F. A. Santos et al., “Antihyperglycemic and hypolipidemic effects of α,β-amyrin, a triterpenoid mixture from Protium heptaphyllum in mice,” Lipids Health Dis., vol. 11, no. 1, pp. 1–8, Aug. 2012, doi: 10.1186/1476-511X-11-98.
- [55] G. F. Aragao, M. C. C. Pinheiro, P. N. Bandeira, T. L. G. Lemos, and G. S. de B. Viana, “Analgesic and Anti-Inflammatory Activities of the Isomeric Mixture of Alpha- and Beta-Amyrin from Protium heptaphyllum(Aubl.) March,” http://dx.doi.org/10.1080/J157v07n02_03, vol. 7, no. 2, pp. 31–47, Jan. 2009, doi: 10.1080/J157V07N02_03.
- [56] L. Fraile, E. Crisci, L. Córdoba, M. A. Navarro, J. Osada, and M. Montoya, “Immunomodulatory properties of Beta-sitosterol in pig immune responses,” Int. Immunopharmacol., vol. 13, no. 3, pp. 316–321, Jul. 2012, doi: 10.1016/J.INTIMP.2012.04.017.
- [57] R. Pompei, O. Flore, M. A. Marccialis, A. Pani, and B. Loddo, “Glycyrrhizic acid inhibits virus growth and inactivates virus particles,” Nat. 1979 2815733, vol. 281, no. 5733, pp. 689–690, 1979, doi: 10.1038/281689a0.
- [58] V. K. Maurya, S. Kumar, M. L. B. Bhatt, and S. K. Saxena, “Antiviral activity of traditional medicinal plants from Ayurveda against SARS-CoV-2 infection,” J. Biomol. Struct. Dyn., vol. 40, no. 4, pp. 1719–1735, 2022, doi: 10.1080/07391102.2020.1832577.
- [59] B. Kar, B. Dehury, M. K. Singh, S. Pati, and D. Bhattacharya, “Identification of phytocompounds as newer antiviral drugs against COVID-19 through molecular docking and simulation based study,” J. Mol. Graph. Model., vol. 114, p. 108192, Jul. 2022, doi: 10.1016/J.JMGM.2022.108192.