Computational studies on searching potential phytochemicals against DNA polymerase activity of the monkeypox virus

10.1016/j.jtcme.2023.04.002

Seshu Vardhan；Suban K. Sahoo

Monkeypox virus ； DNA polymerase ； Phytochemicals ； Molecular docking ； Dynamics simulations

Journal of Traditional and Complementary Medicine

13卷5期（2023 / 09 / 01）

465 - 478

英文

Objectives: The outbreak of monkeypox virus (MPXV) is an emerging epidemic of medical concern with 65353 confirmed cases of infection and a fatality of 115 worldwide. Since May 2022, MPXV has been rapidly disseminating across the globe through various modes of transmission, including direct contact, respiratory droplets, and consensual sex. Because of the limited medical countermeasures available to treat MPXV, the present study aimed to identify potential phytochemicals (limonoids, triterpenoids, and polyphenols) as antagonists to target the DNA polymerase protein of MPXV with the ultimate goal to inhibit the viral DNA replication mechanism and immune-mediated responses. Methods: The protein-DNA and protein-ligand molecular docking were performed with the help of computational programs AutoDock Vina, iGEMDOCK and HDOCK server. The BIOVIA Discovery studio and ChimeraX were used to evaluate the protein-ligand interactions. The GROMACS 2021 was used for the molecular dynamics simulations. The ADME and toxicity properties were computed by using online servers SwissADME and pKCSM. Results: Molecular docking of 609 phytochemicals and molecular dynamics simulations of lead phytochemicals glycyrrhizinic acid and apigenin-7-O-glucuronide generated useful data that supported the ability of phytochemicals to obstruct the DNA polymerase activity of the monkeypox virus. Conclusions: The computational results supported that appropriate phytochemicals can be used to formulate an adjuvant therapy for the monkeypox virus.

1. Sillapachaiyaporn, C,Chuchawankul, S(2020).HIV-1 protease and reverse transcriptase inhibition by tiger milk mushroom (Lignosus rhinocerus) sclerotium extracts: in vitro and in silico studies.J Tradit Complementary Med,10(4),396-404.
   連結：
2. Vardhan, S,Sahoo, SK(2022).Virtual screening by targeting proteolytic sites of furin and TMPRSS2 to propose potential compounds obstructing the entry of SARS-CoV-2 virus into human host cells.J Tradit Complementary Med,12(1),6-15.
   連結：
3. Vardhan, S,Sahoo, SK(2022).Exploring the therapeutic nature of limonoids and triterpenoids against SARS-CoV-2 by targeting nsp13, nsp14, and nsp15 through molecular docking and dynamics simulations.J Tradit Complementary Med,12(1),44-54.
   連結：
4. count Mc www.monkeypoxmeter.com.
5. Abraham, MJ,Murtola, T,Schulz, R(2015).GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers.SoftwareX,1,19-25.
6. Alvarez-Cardona, JJ,Whited, LK,Chemaly, RF(2020).Brincidofovir: understanding its unique profile and potential role against adenovirus and other viral infections.Future Microbiol,15(6),389-400.
7. Andrei, G,Snoeck, R(2010).Cidofovir activity against poxvirus infections.Viruses,2(12),2803-2830.
8. Ayoub, IM,Korinek, M,El-Shazly, M(2021).Anti-allergic, anti-inflammatory, and anti-hyperglycemic activity of Chasmanthe aethiopica leaf extract and its profiling using LC/MS and GLC/MS.Plants,10(6),1118.
9. Banerjee, S,Baidya, SK,Adhikari, N,Ghosh, B,Jha, T(2023).Glycyrrhizin as a promising kryptonite against SARS-CoV-2: clinical, experimental, and theoretical evidences.J Mol Struct,1275,134642.
10. Berhanu, A,Prigge, JT,Silvera, PM,Honeychurch, KM,Hruby, DE,Grosenbach, DW(2015).Treatment with the smallpox antiviral tecovirimat (ST-246) alone or in combination with ACAM2000 vaccination is effective as a postsymptomatic therapy for monkeypox virus infection.Antimicrob Agents Chemother,59(7),4296-4300.
11. Boeing, T,De Souza, P,Speca, S(2020).Luteolin prevents irinotecan-induced intestinal mucositis in mice through antioxidant and anti-inflammatory properties.Br J Pharmacol,177(10),2393-2408.
12. Chen, Z,Duan, H,Tong, X(2017).Cytotoxicity, hemolytic toxicity, and mechanism of action of Pulsatilla saponin D and its synthetic derivatives.J Nat Prod,81(3),465-474.
13. Cherng, J-M,Lin, H-J,Hsu, Y-H,Hung, M-S,Lin, J-C(2004).A quantitative bioassay for HIV-1 gene expression based on UV activation: effect of glycyrrhizic acid.Antivir Res,62(1),27-36.
14. Cinatl, J,Morgenstern, B,Bauer, G,Chandra, P,Rabenau, H,Doerr, H(2003).Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus.Lancet,361(9374),2045-2046.
15. Clercq, ED(2004).Antivirals and antiviral strategies.Nat Rev Microbiol,2(9),704-720.
16. Czarnecki, MW,Traktman, P(2017).The vaccinia virus DNA polymerase and its processivity factor.Virus Res,234,193-206.
17. Estep, RD,Messaoudi, I,O'Connor, MA(2011).Deletion of the monkeypox virus inhibitor of complement enzymes locus impacts the adaptive immune response to monkeypox virus in a nonhuman primate model of infection.J Virol,85(18),9527-9542.
18. Goddard, TD,Huang, CC,Meng, EC(2018).UCSF ChimeraX: meeting modern challenges in visualization and analysis.Protein Sci,27(1),14-25.
19. Goldstein, JA,Neff, JM,Lane, JM,Koplan, JP(1975).Smallpox vaccination reactions, prophylaxis, and therapy of complications.Pediatrics,55(3),342-347.
20. Gulati, P,Chadha, J,Harjai, K,Singh, S(2022).Targeting envelope proteins of poxviruses to repurpose phytochemicals against monkeypox: an in silico Investigation.Front Microbiol,13,1073419.
21. Hammarlund, E,Dasgupta, A,Pinilla, C,Norori, P,Früh, K,Slifka, MK(2008).Monkeypox virus evades antiviral CD4þ and CD8þ T cell responses by suppressing cognate T cell activation.Proc Natl Acad Sci USA,105(38),14567-14572.
22. Hengpratom, T(2018).School of Preclinic Institute of Science, Suranaree University of Technology.
23. Hogg, M,Aller, P,Konigsberg, W,Wallace, SS,Doublie, S(2007).Structural and biochemical investigation of the role in proofreading of a b hairpin loop found in the exonuclease domain of a replicative DNA polymerase of the B family.J Biol Chem,282(2),1432-1444.
24. Hutson, CL,Kondas, AV,Mauldin, MR(2021).Pharmacokinetics and efficacy of a potential smallpox therapeutic, brincidofovir, in a lethal monkeypox virus animal model.mSphere,6(1)
25. Isbrucker, R,Burdock, G(2006).Risk and safety assessment on the consumption of Licorice root (Glycyrrhiza sp.), its extract and powder as a food ingredient, with emphasis on the pharmacology and toxicology of glycyrrhizin.Regul Toxicol Pharmacol,46(3),167-192.
26. Issa, TB,Sagaama, A,Issaoui, N(2020).Computational study of 3-thiophene acetic acid: molecular docking, electronic and intermolecular interactions investigations.Comput Biol Chem,86,107268.
27. Kikuchi, T,Ishii, K,Noto, T(2011).Cytotoxic and apoptosis-inducing activities of limonoids from the seeds of Azadirachta indica (neem).J Nat Prod,74(4),866-870.
28. Kobayashi, R,Hanaya, K,Shoji, M,Ohba, S,Sugai, T(2013).Synthesis of okicamelliaside, a glucoside of ellagic acid with potent anti-degranulation activity.Biosci, Biotechnol, Biochem,77(4),810-813.
29. Koga, K,Tomoyama, M,Ohyanagi, K,Suzuki, T,Hamada, Y(2008).Approach to enhancing the distribution of glycyrrhizin in the liver: intravenous infusion studies in a rat model of bile duct ligation.J Drug Deliv Sci Technol,18(3),161-167.
30. Kondratenko, R,Baltina, L,La, B,Plyasunova, O,Pokrovskii, A,Tolstikov, G(2009).Synthesis of new hetero-and carbocyclic aromatic amides of glycyrrhizic acid as potential anti-HIV agents.Pharm Chem J,43(7),383-388.
31. Kumar, N,Acharya, A,Gendelman, HE,Byrareddy, SN(2022).The 2022 outbreak and the pathobiology of the monkeypox virus.J Autoimmun,2022,102855.
32. Kumari, R,Kumar, R,Consortium, OSDD,Lynn, A(2014).g_mmpbsaeeA GROMACS tool for high-throughput MM-PBSA calculations.J Chem Inf Model,54(7),1951-1962.
33. Lam, HYI,Guan, JS,Mu, Y(2022).In silico repurposed drugs against monkeypox virus.Molecules,27(16),5277.
34. Li, J,Shi, J,Sun, Y,Zheng, F(2018).Glycyrrhizin, a potential drug for autoimmune encephalomyelitis by inhibiting high-mobility group box 1.DNA Cell Biol,37(12),941-946.
35. Likos, AM,Sammons, SA,Olson, VA(2005).A tale of two clades: monkeypox viruses.J Gen Virol,86(10),2661-2672.
36. Magee, WC,Aldern, KA,Hostetler, KY,Evans, DH(2008).Cidofovir and (S)-9-[3-hydroxy-(2-phosphonomethoxy) propyl] adenine are highly effective inhibitors of vaccinia virus DNA polymerase when incorporated into the template strand.Antimicrob Agents Chemother,52(2),586-597.
37. Marrassini, C,Cogoi, L,Sülsen, V,Anesini, C(2020).Apigenin-7-Glucuronide from urera aurantiaca inhibits tumor necrosis factor alpha and total nitrite release in lipopolysaccharide-activated macrophages.Evid Base Compl Alternative Med,2020
38. McCollum, AM,Damon, IK(2014).Human monkeypox.Clin Infect Dis,58(2),260-267.
39. Min, H-Y,Jang, H-J,Park, KH(2019).The natural compound gracillin exerts potent antitumor activity by targeting mitochondrial complex II.Cell Death Dis,10(11),1-18.
40. Minda, D,Avram, S,Pavel, IZ(2020).An in vitro evaluation of apigenin and apigenin-7-o-glucoside against hela human cervical cancer cell line.Rev Chem,71(2),140-144.
41. Mullan, L(2006).Pairwise sequence alignmentdit's all about us.Briefings Bioinf,7(1),113-115.
42. Nuth, M,Huang, L,Saw, YL,Schormann, N,Chattopadhyay, D,Ricciardi, RP(2011).Identification of inhibitors that block vaccinia virus infection by targeting the DNA synthesis processivity factor D4.J Med Chem,54(9),3260-3267.
43. Patel, M,Bazaid, AS,Azhar, EI(2023).Novel phytochemical inhibitors targeting monkeypox virus thymidine and serine/threonine kinase: integrating computational modeling and molecular dynamics simulation.J Biomol Struct Dyn,1-17.
44. Reynolds, MG,McCollum, AM,Nguete, B,Shongo Lushima, R,Petersen, BW(2017).Improving the care and treatment of monkeypox patients in low-resource settings: applying evidence from contemporary biomedical and smallpox biodefense research.Viruses,9(12),380.
45. Rizk, JG,Lippi, G,Henry, BM,Forthal, DN,Rizk, Y(2022).Prevention and treatment of monkeypox.Drugs,1-7.
46. Russo, AT,Grosenbach, DW,Chinsangaram, J(2021).An overview of tecovirimat for smallpox treatment and expanded anti-orthopoxvirus applications.Expert Rev Anti-infective Ther,19(3),331-344.
47. Sele, C,Gabel, F,Gutsche, I(2013).Low-resolution structure of vaccinia virus DNA replication machinery.J Virol,87(3),1679-1689.
48. Shaikh, F,Tai, HK,Desai, N,Siu, SW(2021).LigTMap: ligand and structure-based target identification and activity prediction for small molecular compounds.J Cheminf,13(1),1-12.
49. Sklenovska, N,Van Ranst, M(2018).Emergence of monkeypox as the most important orthopoxvirus infection in humans.Front Public Health,6,241.
50. Son, MK,Jung, KH,Hong, S-W(2013).Pulsatilla saponinD suppresses the proliferation of human colon cancer cells and induces apoptosis by modulating the AKT/mTOR signalling pathway.Food Chem,136(1),26-33.
51. Song, H,Josleyn, N,Janosko, K(2013).Monkeypox virus infection of rhesus macaques induces massive expansion of natural killer cells but suppresses natural killer cell functions.PLoS One,8(10),e77804.
52. Stabenow, J,Buller, RM,Schriewer, J,West, C,Sagartz, JE,Parker, S(2010).A mouse model of lethal infection for evaluating prophylactics and therapeutics against Monkeypox virus.J Virol,84(8),3909-3920.
53. Suraweera, CD,Hinds, MG,Kvansakul, M(2020).Poxviral strategies to overcome host cell apoptosis.Pathogens,10(1),6.
54. Tahir ul Qamar, M,Maryam, A,Muneer, I(2019).Computational screening of medicinal plant phytochemicals to discover potent pan-serotype inhibitors against dengue virus.Sci Rep,9(1),1-16.
55. Tahrani A(2011).The Ruperto-Carola University of Heidelberg.
56. Tarbouriech, N,Ducournau, C,Hutin, S(2017).The vaccinia virus DNA polymerase structure provides insights into the mode of processivity factor binding.Nat Commun,8(1),1-12.
57. Trott, O,Olson, AJ(2010).AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading.J Comput Chem,31(2),455-461.
58. Ukiya, M,Sato, D,Kimura, H,Hirai, Y,Nishina, A(2020).Tokoronin contained in Dioscorea tokoro makino ex miyabe suppressed a-MSH-induced melanogenesis in B16 cells via suppression of classical MAPK pathway activation.Chem Biodivers,17(6),e2000077.
59. Vardhan, S,Sahoo, SK(2022).Computational studies on the interaction of SARS-CoV-2 Omicron SGp RBD with human receptor ACE2, limonin and glycyrrhizic acid.Comput Biol Med,144,105367.
60. Vardhan, S,Sahoo, SK(2020).In silico ADMET and molecular docking study on searching potential inhibitors from limonoids and triterpenoids for COVID-19.Comput Biol Med,124,103936.
61. Wenham, C,Eccleston-Turner, M(2022).Monkeypox as a PHEIC: Implications for Global Health Governance.Lancet
62. Wu, S-y,Wang, W-j,Dou, J-h,Gong, L-k(2021).Research progress on the protective effects of licorice-derived 18b-glycyrrhetinic acid against liver injury.Acta Pharmacol Sin,42(1),18-26.
63. Xu, B,Li, P,Zhang, G(2015).Comparative pharmacokinetics of puerarin, daidzin, baicalin, glycyrrhizic acid, liquiritin, berberine, palmatine and jateorhizine by liquid chromatographyemass spectrometry after oral administration of Gegenqinlian decoction and active components alignment (ACA) to rats.J Chromatogr B,988,33-44.
64. Yang, G,Pevear, DC,Davies, MH(2005).An orally bioavailable antipoxvirus compound (ST-246) inhibits extracellular virus formation and protects mice from lethal orthopoxvirus challenge.J Virol,79(20),13139-13149.
65. Yang, J,Cao, L,Li, Y(2021).Gracillin isolated from Reineckia carnea induces apoptosis of A549 Cells via the mitochondrial pathway.Drug Des Dev Ther,15,233.
66. Yu, S,Zhu, Y,Xu, J(2021).Glycyrrhizic acid exerts inhibitory activity against the spike protein of SARS-CoV-2.Phytomedicine,85,153364.
67. Zhang, S,Kumar, K,Jiang, X,Wallqvist, A,Reifman, J(2008).DOVIS: an implementation for high-throughput virtual screening using AutoDock.BMC Bioinf,9(1),1-4.
68. Zheng, L,Meng, J,Lin, M(2022).Structure prediction of the entire proteome of monkeypox variants.Acta Mater Med