Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

An In-silico Approach to Design and Validate siRNA against Monkeypox Virus

Author(s): Kishore Dhotre, Anwesha Banerjee, Debashree Dass, Vijay Nema and Anupam Mukherjee*

Volume 29, Issue 38, 2023

Published on: 07 December, 2023

Page: [3060 - 3072] Pages: 13

DOI: 10.2174/0113816128275065231103063935

Price: $65

Abstract

Introduction: The monkeypox virus has emerged as an uncommon zoonotic infection. The recent outbreak of MPXV in Europe and abroad in 2022 presented a major threat to individuals at risk. At present, no specific MPXV vaccinations or medications are available.

Methods: In this study, we predicted the most effective siRNA against the conserved region of the MPXV and validated the activity by performing molecular docking studies.

Results: Ultimately, the most efficient siRNA molecule was shortlisted against the envelope protein gene (B6R) based on its toxicity, effectivity, thermodynamic stability, molecular interaction, and molecular dynamics simulations (MD) with the Human Argonaute 2 protein.

Conclusion: Thus, the strategy may offer a platform for the development of potential antiviral RNA therapeutics that target MPXV at the genomic level.

Keywords: Monkeypox, small interfering RNA, RNAi, molecular docking, therapeutics, zoonotic infection.

« Previous Next »
[1]
Thornhill JP, Barkati S, Walmsley S, et al. Monkeypox virus infection in humans across 16 countries - April-June 2022. N Engl J Med 2022; 387(8): 679-91.
[http://dx.doi.org/10.1056/NEJMoa2207323]
[2]
Weaver JR, Isaacs SN. Monkeypox virus and insights into its immunomodulatory proteins. Immunol Rev 2008; 225(1): 96-113.
[http://dx.doi.org/10.1111/j.1600-065X.2008.00691.x] [PMID: 18837778]
[3]
Hammarlund E, Dasgupta A, Pinilla C, Norori P, Früh K, Slifka MK. Monkeypox virus evades antiviral CD4+ and CD8+ T cell responses by suppressing cognate T cell activation. Proc Natl Acad Sci USA 2008; 105(38): 14567-72.
[http://dx.doi.org/10.1073/pnas.0800589105] [PMID: 18796610]
[4]
Gong Q, Wang C, Chuai X, Chiu S. Monkeypox virus: A re-emergent threat to humans. Virologica Sinica 2022. S1995820X22001201
[http://dx.doi.org/10.1016/j.virs.2022.07.006]
[5]
Shaheen N, Diab RA, Meshref M, Shaheen A, Ramadan A, Shoib S. Is there a need to be worried about the new monkeypox virus outbreak? A brief review on the monkeypox outbreak. Ann Med Surg 2022; 81: 104396.
[http://dx.doi.org/10.1016/j.amsu.2022.104396] [PMID: 36147131]
[6]
Ihekweazu C, Yinka-Ogunleye A, Lule S, Ibrahim A. Importance of epidemiological research of monkeypox: Is incidence increasing? Expert Rev Anti Infect Ther 2020; 18(5): 389-92.
[http://dx.doi.org/10.1080/14787210.2020.1735361] [PMID: 32096659]
[7]
Morgan CN, Whitehill F, Doty JB, et al. Environmental persistence of monkeypox virus on surfaces in household of person with travel-associated infection, Dallas, Texas, USA, 2021. Emerg Infect Dis 2022; 28(10): 1982-9.
[http://dx.doi.org/10.3201/eid2810.221047] [PMID: 35951009]
[8]
Rabaan AA, Al-Shwaikh SA, Alfouzan WA, et al. A comprehensive review on monkeypox viral disease with potential diagnostics and therapeutic options. Biomedicines 2023; 11(7): 1826.
[http://dx.doi.org/10.3390/biomedicines11071826] [PMID: 37509466]
[9]
Kupferschmidt K. Why monkeypox is mostly hitting men who have sex with men. Science 2022; 376(6600): 1364-5.
[http://dx.doi.org/10.1126/science.add5966] [PMID: 35737802]
[10]
Monkeypox WHO. COVID-19 & Other Global Health Issues Virtual Press Conference Transcript - 17 August 2022.
[11]
Isidro J, Borges V, Pinto M, et al. Phylogenomic characterization and signs of microevolution in the 2022 multi-country outbreak of monkeypox virus. Nat Med 2022; 28(8): 1569-72.
[http://dx.doi.org/10.1038/s41591-022-01907-y] [PMID: 35750157]
[12]
Rizk JG, Lippi G, Henry BM, Forthal DN, Rizk Y. Prevention and treatment of monkeypox. Drugs 2022; 82(9): 957-63.
[http://dx.doi.org/10.1007/s40265-022-01742-y] [PMID: 35763248]
[13]
Russo AT, Grosenbach DW, Chinsangaram J, et al. An overview of tecovirimat for smallpox treatment and expanded anti-orthopoxvirus applications. Expert Rev Anti Infect Ther 2021; 19(3): 331-44.
[http://dx.doi.org/10.1080/14787210.2020.1819791] [PMID: 32882158]
[14]
Lanier R, Trost L, Tippin T, et al. Development of CMX001 for the treatment of poxvirus infections. Viruses 2010; 2(12): 2740-62.
[http://dx.doi.org/10.3390/v2122740] [PMID: 21499452]
[15]
Wittek R. Vaccinia immune globulin: Current policies, preparedness, and product safety and efficacy. Int J Infect Dis 2006; 10(3): 193-201.
[http://dx.doi.org/10.1016/j.ijid.2005.12.001] [PMID: 16564720]
[16]
Tan FL, Yin JQ. RNAi, a new therapeutic strategy against viral infection. Cell Res 2004; 14(6): 460-6.
[http://dx.doi.org/10.1038/sj.cr.7290248] [PMID: 15625012]
[17]
Zogg H, Singh R, Ro S. Current advances in RNA therapeutics for human diseases. Int J Mol Sci 2022; 23(5): 2736.
[http://dx.doi.org/10.3390/ijms23052736] [PMID: 35269876]
[18]
Lee MJ, Lee I, Wang K. Recent advances in RNA therapy and its carriers to treat the single-gene neurological disorders. Biomedicines 2022; 10(1): 158.
[http://dx.doi.org/10.3390/biomedicines10010158] [PMID: 35052837]
[19]
Ui-Tei K, Naito Y, Takahashi F, et al. Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference. Nucleic Acids Res 2004; 32(3): 936-48.
[http://dx.doi.org/10.1093/nar/gkh247] [PMID: 14769950]
[20]
Reynolds A, Leake D, Boese Q, Scaringe S, Marshall WS, Khvorova A. Rational siRNA design for RNA interference. Nat Biotechnol 2004; 22(3): 326-30.
[http://dx.doi.org/10.1038/nbt936] [PMID: 14758366]
[21]
Matveeva OV, Nazipova NN, Ogurtsov AY, Shabalina SA. Optimized models for design of efficient miR30-based shRNAs. Front Genet 2012; 3: 163.
[http://dx.doi.org/10.3389/fgene.2012.00163] [PMID: 22952469]
[22]
Chowdhury UF, Sharif Shohan MU, Hoque KI, Beg MA, Sharif Siam MK, Moni MA. A computational approach to design potential siRNA molecules as a prospective tool for silencing nucleocapsid phosphoprotein and surface glycoprotein gene of SARS-CoV- 2. Genomics 2021; 113(1): 331-43.
[http://dx.doi.org/10.1016/j.ygeno.2020.12.021] [PMID: 33321203]
[23]
Ui-Tei K, Naito Y, Nishi K, Juni A, Saigo K. Thermodynamic stability and Watson–Crick base pairing in the seed duplex are major determinants of the efficiency of the siRNA-based off-target effect. Nucleic Acids Res 2008; 36(22): 7100-9.
[http://dx.doi.org/10.1093/nar/gkn902] [PMID: 18988625]
[24]
Fine PEM, Jezek Z, Grab B, Dixon H. The transmission potential of monkeypox virus in human populations. Int J Epidemiol 1988; 17(3): 643-50.
[http://dx.doi.org/10.1093/ije/17.3.643] [PMID: 2850277]
[25]
Tamura K, Stecher G, Kumar S. MEGA11: Molecular evolutionary genetics analysis version 11. Mol Biol Evol 2021; 38(7): 3022-7.
[http://dx.doi.org/10.1093/molbev/msab120] [PMID: 33892491]
[26]
Li Y, Olson VA, Laue T, Laker MT, Damon IK. Detection of monkeypox virus with real-time PCR assays. J Clin Virol 2006; 36(3): 194-203.
[http://dx.doi.org/10.1016/j.jcv.2006.03.012] [PMID: 16731033]
[27]
Reynolds MG, Suu-Ire R, Karem K, et al. A silent enzootic of an orthopoxvirus in Ghana, West Africa: Evidence for multi-species involvement in the absence of widespread human disease. Am J Trop Med Hyg 2010; 82(4): 746-54.
[http://dx.doi.org/10.4269/ajtmh.2010.09-0716] [PMID: 20348530]
[28]
Naito Y, Yoshimura J, Morishita S, Ui-Tei K. siDirect 2.0: Updated software for designing functional siRNA with reduced seed-dependent off-target effect. BMC Bioinf 2009; 10(1): 392.
[http://dx.doi.org/10.1186/1471-2105-10-392] [PMID: 19948054]
[29]
Madanagopal P, Muthukumar H, Thiruvengadam K. Computational study and design of effective siRNAs to silence structural proteins associated genes of Indian SARS-CoV-2 strains. Comput Biol Chem 2022; 98: 107687.
[http://dx.doi.org/10.1016/j.compbiolchem.2022.107687] [PMID: 35537364]
[30]
Amarzguioui M, Prydz H. An algorithm for selection of functional siRNA sequences. Biochem Biophys Res Commun 2004; 316(4): 1050-8.
[http://dx.doi.org/10.1016/j.bbrc.2004.02.157] [PMID: 15044091]
[31]
Kibbe WA. OligoCalc: An online oligonucleotide properties calculator. Nucleic Acids Res 2007; 35(Web Server): W43-6.
[http://dx.doi.org/10.1093/nar/gkm234] [PMID: 17452344]
[32]
Bellaousov S, Reuter JS, Seetin MG, Mathews DH. RNAstructure: Web servers for RNA secondary structure prediction and analysis. Nucleic Acids Res 2013; 41(W1): W471-4.
[http://dx.doi.org/10.1093/nar/gkt290] [PMID: 23620284]
[33]
Markham NR, Zuker M. DINAMelt web server for nucleic acid melting prediction. Nucleic Acids Res 2005; 33(Web Server): W577-81.
[http://dx.doi.org/10.1093/nar/gki591] [PMID: 15980540]
[34]
Meister G, Landthaler M, Patkaniowska A, Dorsett Y, Teng G, Tuschl T. Human argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell 2004; 15(2): 185-97.
[http://dx.doi.org/10.1016/j.molcel.2004.07.007] [PMID: 15260970]
[35]
Heo L, Park H, Seok C. GalaxyRefine: Protein structure refinement driven by side-chain repacking. Nucleic Acids Res 2013; 41(W1): W384-8.
[http://dx.doi.org/10.1093/nar/gkt458] [PMID: 23737448]
[36]
Laskowski RA, MacArthur MW, Moss DS, Thornton JM. PROCHECK: A program to check the stereochemical quality of protein structures. J Appl Cryst 1993; 26(2): 283-91.
[http://dx.doi.org/10.1107/S0021889892009944]
[37]
Wiederstein M, Sippl MJ. ProSA-web: Interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Res 2007; 35(Web Server): W407-10.
[http://dx.doi.org/10.1093/nar/gkm290] [PMID: 17517781]
[38]
Zuker M. Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res 2003; 31(13): 3406-15.
[http://dx.doi.org/10.1093/nar/gkg595] [PMID: 12824337]
[39]
Popenda M, Szachniuk M, Antczak M, et al. Automated 3D structure composition for large RNAs. Nucleic Acids Res 2012; 40(14): e112-2.
[http://dx.doi.org/10.1093/nar/gks339] [PMID: 22539264]
[40]
Yan Y, Zhang D, Zhou P, Li B, Huang SY. HDOCK: A web server for protein-protein and protein-DNA/RNA docking based on a hybrid strategy. Nucleic Acids Res 2017; 45(W1): W365-73.
[http://dx.doi.org/10.1093/nar/gkx407] [PMID: 28521030]
[41]
Elkayam E, Kuhn CD, Tocilj A, et al. The structure of human argonaute-2 in complex with miR-20a. Cell 2012; 150(1): 100-10.
[http://dx.doi.org/10.1016/j.cell.2012.05.017] [PMID: 22682761]
[42]
Adasme MF, Linnemann KL, Bolz SN, et al. PLIP 2021: Expanding the scope of the protein–ligand interaction profiler to DNA and RNA. Nucleic Acids Res 2021; 49(W1): W530-4.
[http://dx.doi.org/10.1093/nar/gkab294] [PMID: 33950214]
[43]
Kumar S, Nussinov R. Close-range electrostatic interactions in proteins. ChemBioChem 2002; 3(7): 604-17.
[http://dx.doi.org/10.1002/1439-7633(20020703)3:7<604::AID-CBIC604>3.0.CO;2-X] [PMID: 12324994]
[44]
Tolstorukov MY, Jernigan RL, Zhurkin VB. Protein-DNA hydrophobic recognition in the minor groove is facilitated by sugar switching. J Mol Biol 2004; 337(1): 65-76.
[http://dx.doi.org/10.1016/j.jmb.2004.01.011] [PMID: 15001352]
[45]
Kalra K, Gorle S, Cavallo L, Oliva R, Chawla M. Occurrence and stability of lone pair-π and OH–π interactions between water and nucleobases in functional RNAs. Nucleic Acids Res 2020; 48(11): 5825-38.
[http://dx.doi.org/10.1093/nar/gkaa345] [PMID: 32392301]
[46]
Corley M, Burns MC, Yeo GW. How RNA-binding proteins interact with RNA: Molecules and mechanisms. Mol Cell 2020; 78(1): 9-29.
[http://dx.doi.org/10.1016/j.molcel.2020.03.011] [PMID: 32243832]
[47]
Van Der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, Berendsen HJC. GROMACS: Fast, flexible, and free. J Comput Chem 2005; 26(16): 1701-18.
[http://dx.doi.org/10.1002/jcc.20291] [PMID: 16211538]
[48]
Hornak V, Abel R, Okur A, Strockbine B, Roitberg A, Simmerling C. Comparison of multiple Amber force fields and development of improved protein backbone parameters. Proteins 2006; 65(3): 712-25.
[http://dx.doi.org/10.1002/prot.21123] [PMID: 16981200]
[49]
Shawan MMAK, Sharma AR, Bhattacharya M, et al. Designing an effective therapeutic siRNA to silence RdRp gene of SARS- CoV-2. Infect Genet Evol 2021; 93: 104951.
[http://dx.doi.org/10.1016/j.meegid.2021.104951] [PMID: 34089909]
[50]
Amiri A, Barreto G, Sathyapalan T, Sahebkar A. siRNA therapeutics: Future promise for neurodegenerative diseases. CN 2021; 19: 1896-911.
[http://dx.doi.org/10.2174/1570159X19666210402104054]
[51]
Müller M, Fazi F, Ciaudo C. Argonaute proteins: From structure to function in development and pathological cell fate determination. Front Cell Dev Biol 2020; 7: 360.
[http://dx.doi.org/10.3389/fcell.2019.00360] [PMID: 32039195]
[52]
Boland A, Tritschler F, Heimstädt S, Izaurralde E, Weichenrieder O. Crystal structure and ligand binding of the MID domain of a eukaryotic argonaute protein. EMBO Rep 2010; 11(7): 522-7.
[http://dx.doi.org/10.1038/embor.2010.81] [PMID: 20539312]
[53]
Kandeel M, Kitade Y. Computational analysis of siRNA recognition by the Ago2 PAZ domain and identification of the determinants of RNA-induced gene silencing. PLoS One 2013; 8(2): e57140.
[http://dx.doi.org/10.1371/journal.pone.0057140] [PMID: 23441235]
[54]
Shi H, Ullu E, Tschudi C. Function of the trypanosome argonaute 1 protein in rna interference requires the n-terminal rgg domain and arginine 735 in the piwi domain. J Biol Chem 2004; 279(48): 49889-93.
[http://dx.doi.org/10.1074/jbc.M409280200] [PMID: 15383544]
[55]
Ekins S, Mestres J, Testa B. In silico pharmacology for drug discovery: Methods for virtual ligand screening and profiling. Br J Pharmacol 2007; 152(1): 9-20.
[http://dx.doi.org/10.1038/sj.bjp.0707305] [PMID: 17549047]
[56]
ElHefnawi M, Kim T, Kamar MA, et al. In silico design and experimental validation of sirnas targeting conserved regions of multiple hepatitis C virus genotypes. PLoS One 2016; 11(7): e0159211.
[http://dx.doi.org/10.1371/journal.pone.0159211] [PMID: 27441640]
[57]
Sohrab SS, Aly El-Kafrawy S, Mirza Z, Hassan AM, Alsaqaf F, Azhar EI. In silico prediction and experimental validation of siRNAs targeting ORF1ab of MERS-CoV in vero cell line. Saudi J Biol Sci 2021; 28(2): 1348-55.
[http://dx.doi.org/10.1016/j.sjbs.2020.11.066] [PMID: 33519276]
[58]
Dana H, Chalbatani GM, Mahmoodzadeh H, et al. Molecular mechanisms and biological functions of siRNA. Int J Biomed Sci 2017; 13(2): 48.
[http://dx.doi.org/10.59566/IJBS.2017.13048]
[59]
Yonezawa S, Koide H, Asai T. Recent advances in siRNA delivery mediated by lipid-based nanoparticles. Adv Drug Deliv Rev 2020; 154-155: 64-78.
[http://dx.doi.org/10.1016/j.addr.2020.07.022] [PMID: 32768564]
[60]
DiFiglia M, Sena-Esteves M, Chase K, et al. Therapeutic silencing of mutant huntingtin with siRNA attenuates striatal and cortical neuropathology and behavioral deficits. Proc Natl Acad Sci USA 2007; 104(43): 17204-9.
[http://dx.doi.org/10.1073/pnas.0708285104] [PMID: 17940007]
[61]
Defougerolles A, Novobrantseva T. siRNA and the lung: Research tool or therapeutic drug? Curr Opin Pharmacol 2008; 8(3): 280-5.
[http://dx.doi.org/10.1016/j.coph.2008.04.005] [PMID: 18485820]
[62]
Gao S, Dagnaes-Hansen F, Nielsen EJB, et al. The effect of chemical modification and nanoparticle formulation on stability and biodistribution of siRNA in mice. Mol Ther 2009; 17(7): 1225-33.
[http://dx.doi.org/10.1038/mt.2009.91] [PMID: 19401674]
[63]
Iversen F, Yang C, Dagnæs-Hansen F, Schaffert DH, Kjems J, Gao S. Optimized siRNA-PEG conjugates for extended blood circulation and reduced urine excretion in mice. Theranostics 2013; 3(3): 201-9.
[http://dx.doi.org/10.7150/thno.5743] [PMID: 23471415]
[64]
Hobbs SK, Monsky WL, Yuan F, et al. Regulation of transport pathways in tumor vessels: Role of tumor type and microenvironment. Proc Natl Acad Sci USA 1998; 95(8): 4607-12.
[http://dx.doi.org/10.1073/pnas.95.8.4607] [PMID: 9539785]
[65]
Torchilin VP, Trubetskoy VS. Which polymers can make nanoparticulate drug carriers long-circulating? Adv Drug Deliv Rev 1995; 16(2-3): 141-55.
[http://dx.doi.org/10.1016/0169-409X(95)00022-Y]
[66]
Jhaveri AM, Torchilin VP. Multifunctional polymeric micelles for delivery of drugs and siRNA. Front Pharmacol 2014; 5: 77.
[http://dx.doi.org/10.3389/fphar.2014.00077] [PMID: 24795633]
[67]
Hoff N, Doshi R, Colwell B, et al. Evolution of a disease surveillance system: An increase in reporting of human monkeypox disease in the democratic republic of the congo, 2001-2013. Int J Trop Dis Health 2017; 25(2): 1-10.
[http://dx.doi.org/10.9734/IJTDH/2017/35885] [PMID: 30123790]

Rights & Permissions Print Cite
Article Metrics
37
3
Wayfinder Image
World Antimicrobial Awareness Week
© 2024 Bentham Science Publishers | Privacy Policy