{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T04:57:19Z","timestamp":1782017839139,"version":"3.54.5"},"reference-count":65,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Clemson University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Despite various methods for detecting and treating SARS-CoV-2, affordable and easily applicable solutions are still needed. Aptamers can potentially fill this gap. Here, we establish a workflow to identify aptamers that bind to the spike proteins of SARS-CoV-2, a process applicable to other targets as well. The spike protein is crucial for the virus\u2019s entry into host cells. The aptamer development process for the spike protein\u2019s receptor binding domain (RBD) begins with splitting the SARS-CoV-2\u2019s genome into 40 nucleotide-long sequences, predicting their two-dimensional structure, and sorting based on the free energy. Selected oligomers undergo three-dimensional structure prediction and docking onto the viral spike protein\u2019s RBD. Six RNA oligomers were identified as top candidates based on the RNA docking with the SARS-CoV-2 wild-type (WT) (Wuhan-Hu-1 strain) and Omicron variant BA.1 RBD and molecular dynamics simulations. Three oligomers also demonstrated strong predicted binding affinity with other SARS-CoV-2 variants, including BA.2, XBB.1.5, and EG.5, based on the protein\u2013aptamer docking followed by stability evaluation using the MD simulations. The aptamer with the best fit for the spike protein RBD was later validated using biolayer interferometry. The process has resulted in identifying a single aptamer from a library of 29,000 RNA oligomers, which exhibited affinity in the submicromolar range and the potential to develop into a viral screen or therapeutic.<\/jats:p>","DOI":"10.3390\/biom15060805","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T12:27:09Z","timestamp":1748867229000},"page":"805","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Aptamer Development for SARS-CoV-2 and Omicron Variants Using the Spike Protein Receptor Binding Domain as a Potential Diagnostic Tool and Therapeutic Agent"],"prefix":"10.3390","volume":"15","author":[{"given":"Prasanna V.","family":"Shekar","sequence":"first","affiliation":[{"name":"Department of Plant and Environmental Sciences, Clemson University Pee Dee Research and Education Center, Florence, SC 29506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5023-7618","authenticated-orcid":false,"given":"Anuj","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dalhousie University, Halifax, NS B3H 4R2, Canada"},{"name":"Department of Pediatrics, IWK Health Center, Canadian Centre for Vaccinology CCfV, Halifax, NS B3H 4R2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4607-8391","authenticated-orcid":false,"given":"Nirmitee","family":"Mulgaonkar","sequence":"additional","affiliation":[{"name":"Biological and Agricultural Engineering Department, Texas A&M University, College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samneet","family":"Kashyap","sequence":"additional","affiliation":[{"name":"Department of Plant and Environmental Sciences, Clemson University Pee Dee Research and Education Center, Florence, SC 29506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gourav","family":"Choudhir","sequence":"additional","affiliation":[{"name":"Centre for Rural Development & Technology, Indian Institute of Technology (IIT), New Delhi 110016, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7692-2170","authenticated-orcid":false,"given":"Sandun","family":"Fernando","sequence":"additional","affiliation":[{"name":"Biological and Agricultural Engineering Department, Texas A&M University, College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6881-9501","authenticated-orcid":false,"given":"Sachin","family":"Rustgi","sequence":"additional","affiliation":[{"name":"Department of Plant and Environmental Sciences, Clemson University Pee Dee Research and Education Center, Florence, SC 29506, USA"},{"name":"School of Health Research, Clemson University, Clemson, SC 29634, USA"},{"name":"Center for Human Genetics, Clemson University, Greenwood, SC 29646, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,1]]},"reference":[{"key":"ref_1","unstructured":"(2023, November 28). Coronavirus COVID-19 (SARS-CoV-2)|Johns Hopkins ABX Guide. Available online: https:\/\/www.hopkinsguides.com\/hopkins\/view\/Johns_Hopkins_ABX_Guide\/540747\/all\/Coronavirus_COVID_19__SARS_CoV_2_."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Coronaviridae Study Group of the International Committee on Taxonomy of Viruses (2020). The species Severe acute respiratory syndrome-related coronavirus: Classifying 2019-nCoV and naming it SARS-CoV-2. Nat. Microbiol., 5, 536\u2013544.","DOI":"10.1038\/s41564-020-0695-z"},{"key":"ref_3","unstructured":"(2023, November 28). WHO Coronavirus (COVID-19) Dashboard|WHO Coronavirus (COVID-19) Dashboard with Vaccination Data. Available online: https:\/\/covid19.who.int\/."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1038\/s41401-020-0485-4","article-title":"Structural and functional properties of SARS-CoV-2 spike protein: Potential antivirus drug development for COVID-19","volume":"41","author":"Huang","year":"2020","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1126\/science.abb2507","article-title":"Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation","volume":"367","author":"Wrapp","year":"2020","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6306","DOI":"10.1080\/07391102.2020.1796811","article-title":"Targeting SARS-CoV-2 spike protein of COVID-19 with naturally occurring phytochemicals: An in silico study for drug development","volume":"39","author":"Pandey","year":"2020","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5768","DOI":"10.1080\/07391102.2020.1794969","article-title":"Targeting virus\u2013host interaction by novel pyrimidine derivative: An in silico approach towards discovery of potential drug against COVID-19","volume":"39","author":"Rane","year":"2020","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/nrd3141","article-title":"Aptamers as therapeutics","volume":"9","author":"Keefe","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Macke, T.J., and Case, D.A. (1997). Modeling Unusual Nucleic Acid Structures. Molecular Modeling of Nucleic Acids, American Chemical Society.","DOI":"10.1021\/bk-1998-0682.ch024"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/nrd.2016.199","article-title":"Aptamers as targeted therapeutics: Current potential and challenges","volume":"16","author":"Zhou","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"14314","DOI":"10.1021\/jacs.8b08645","article-title":"Identification and Characterization of DNA Aptamers Specific for Phosphorylation Epitopes of Tau Protein","volume":"140","author":"Teng","year":"2018","journal-title":"J. Am. Chem. Soc."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"18066","DOI":"10.1021\/jacs.8b10783","article-title":"Imaging of Neurite Network with an Anti-L1CAM Aptamer Generated by Neurite-SELEX","volume":"140","author":"Wang","year":"2018","journal-title":"J. Am. Chem. Soc."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1007\/s10895-010-0670-9","article-title":"A novel screening method for competitive FRET-aptamers applied to E. coli assay development","volume":"20","author":"Bruno","year":"2010","journal-title":"J. Fluoresc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s10895-008-0429-8","article-title":"Plastic-adherent DNA aptamer-magnetic bead and quantum dot sandwich assay for Campylobacter detection","volume":"19","author":"Bruno","year":"2009","journal-title":"J. Fluoresc."},{"key":"ref_15","first-page":"445","article-title":"Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy","volume":"118","author":"Adamis","year":"1994","journal-title":"Arch. Ophthalmol."},{"key":"ref_16","first-page":"4029","article-title":"Identification and characterization of nuclease-stabilized RNA molecules that bind human prostate cancer cells via the prostate-specific membrane antigen","volume":"62","author":"Lupold","year":"2002","journal-title":"Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1002\/anie.201006630","article-title":"Nucleic acid and peptide aptamers: Fundamentals and bioanalytical aspects","volume":"51","author":"Mascini","year":"2012","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4117","DOI":"10.2174\/092986711797189619","article-title":"Recent Developments in Protein and Cell-Targeted Aptamer Selection and Applications","volume":"18","author":"Liu","year":"2011","journal-title":"Curr. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1039\/b412492h","article-title":"SELEX: Just another separation?","volume":"130","author":"Bowser","year":"2005","journal-title":"Analyst"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.biochi.2017.10.005","article-title":"In silico approaches to RNA aptamer design","volume":"145","author":"Hamada","year":"2018","journal-title":"Biochimie"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/s41563-020-00906-z","article-title":"Diagnostics for SARS-CoV-2 infections","volume":"20","author":"Kevadiya","year":"2021","journal-title":"Nat. Mater."},{"key":"ref_22","unstructured":"(2023, November 28). COVID-19 Testing: What You Need to Know|CDC, Available online: https:\/\/www.cdc.gov\/covid\/testing\/."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e01695-20","DOI":"10.1128\/JCM.01695-20","article-title":"Challenges and Controversies to Testing for COVID-19","volume":"58","author":"Binnicker","year":"2020","journal-title":"J. Clin. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1017\/ice.2020.290","article-title":"RT-PCR tests for SARS-CoV-2 processed at a large Italian Hospital and false-negative results among confirmed COVID-19 cases","volume":"42","author":"Valent","year":"2021","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Vargas-Montes, M., Cardona, N., Moncada, D.M., Molina, D.A., Zhang, Y., and G\u00f3mez-Mar\u00edn, J.E. (2019). Enzyme-Linked Aptamer Assay (ELAA) for Detection of Toxoplasma ROP18 Protein in Human Serum. Front. Cell. Infect. Microbiol., 9.","DOI":"10.3389\/fcimb.2019.00386"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"25846","DOI":"10.1021\/acsomega.1c04024","article-title":"Multiplex Biosensing for Simultaneous Detection of Mutations in SARS-CoV-2","volume":"6","author":"Xi","year":"2021","journal-title":"ACS Omega"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s00604-022-05357-8","article-title":"SARS-CoV-2 virus label-free electrochemical nanohybrid MIP-aptasensor based on Ni3(BTC)2 MOF as a high-performance surface substrate","volume":"189","author":"Rahmati","year":"2022","journal-title":"Microchim. Acta"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kukushkin, V., Ambartsumyan, O., Astrakhantseva, A., Gushchin, V., Nikonova, A., Dorofeeva, A., Zverev, V., Gambaryan, A., Tikhonova, D., and Sovetnikov, T. (2022). Lithographic SERS Aptasensor for Ultrasensitive Detection of SARS-CoV-2 in Biological Fluids. Nanomaterials, 12.","DOI":"10.3390\/nano12213854"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"100757","DOI":"10.1016\/j.imu.2021.100757","article-title":"In silico design of quadruplex aptamers against the spike protein of SARS-CoV-2","volume":"26","author":"Behbahani","year":"2021","journal-title":"Inform. Med. Unlocked"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Andress, C., Kappel, K., Villena, M.E., Cuperlovic-Culf, M., Yan, H., and Li, Y. (2023). DAPTEV: Deep aptamer evolutionary modelling for COVID-19 drug design. PLoS Comput. Biol., 19.","DOI":"10.1371\/journal.pcbi.1010774"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Lin, Y.-C., Chen, W.-Y., Hwu, E.-T., and Hu, W.-P. (2022). In-Silico Selection of Aptamer Targeting SARS-CoV-2 Spike Protein. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23105810"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-62703-755-6_1","article-title":"Computational design of RNA libraries for in vitro selection of aptamers","volume":"1111","author":"Chushak","year":"2014","journal-title":"Methods Mol. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3406","DOI":"10.1093\/nar\/gkg595","article-title":"Mfold web server for nucleic acid folding and hybridization prediction","volume":"31","author":"Zuker","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.ymeth.2016.03.010","article-title":"RNAComposer and RNA 3D structure prediction for nanotechnology","volume":"103","author":"Biesiada","year":"2016","journal-title":"Methods"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Yan, Y., and Huang, S.-Y. (2020). Modeling Protein\u2013Protein or Protein\u2013DNA\/RNA Complexes Using the HDOCK Webserver. Methods in Molecular Biology, Humana.","DOI":"10.1007\/978-1-0716-0708-4_12"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"W530","DOI":"10.1093\/nar\/gkab294","article-title":"PLIP 2021: Expanding the scope of the protein\u2013ligand interaction profiler to DNA and RNA","volume":"49","author":"Adasme","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"159","DOI":"10.21769\/BioProtoc.2051","article-title":"Protocol for Molecular Dynamics Simulations of Proteins","volume":"6","author":"Gajula","year":"2016","journal-title":"Bio-Protocol"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1021\/ar9500675","article-title":"Advances and Continuing Challenges in Achieving Realistic and Predictive Simulations of the Properties of Organic and Biological Molecules","volume":"29","author":"Kollman","year":"1996","journal-title":"Acc. Chem. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1021\/ci500020m","article-title":"G_mmpbsa\u2014A GROMACS tool for high-throughput MM-PBSA calculations","volume":"54","author":"Kumari","year":"2014","journal-title":"J. Chem. Inf. Model."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1007\/s43440-021-00228-0","article-title":"Rifampicin and Letermovir as potential repurposed drug candidate for COVID-19 treatment: Insights from an in-silico study","volume":"73","author":"Pathak","year":"2021","journal-title":"Pharmacol. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6239","DOI":"10.1021\/acs.jafc.2c01591","article-title":"Bio-Layer Interferometry-Based SELEX and Label-Free Detection of Patulin Using Generated Aptamer","volume":"70","author":"Mukherjee","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4399","DOI":"10.1038\/s41467-022-32019-3","article-title":"Structure of SARS-CoV-2 membrane protein essential for virus assembly","volume":"13","author":"Zhang","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Zheng, X., Sun, Z., Yu, L., Shi, D., Zhu, M., Yao, H., and Li, L. (2021). Interactome analysis of the nucleocapsid protein of SARS-CoV-2 virus. Pathogens, 10.","DOI":"10.3390\/pathogens10091155"},{"key":"ref_44","first-page":"27","article-title":"RNA aptamers and their therapeutic and diagnostic applications","volume":"4","author":"Germer","year":"2013","journal-title":"Int. J. Biochem. Mol. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"9895","DOI":"10.1021\/acs.analchem.0c01394","article-title":"Discovery of Aptamers Targeting the Receptor-Binding Domain of the SARS-CoV-2 Spike Glycoprotein","volume":"92","author":"Song","year":"2020","journal-title":"Anal. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e202104481","DOI":"10.1002\/chem.202104481","article-title":"Structure- and Interaction-Based Design of Anti-SARS-CoV-2 Aptamers","volume":"28","author":"Mironov","year":"2022","journal-title":"Chem. Eur. J."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Hewins, B., Rahman, M., Bermejo-Martin, J.F., Kelvin, A.A., Richardson, C.D., Rubino, S., Kumar, A., Ndishimye, P., Ostadgavahi, A.T., and Mahmud-Al-Rafat, A. (2022). Alpha, Beta, Delta, Omicron, and SARS-CoV-2 Breakthrough Cases: Defining Immunological Mechanisms for Vaccine Waning and Vaccine-Variant Mismatch. Front. J. Women Stud., 2.","DOI":"10.3389\/fviro.2022.849936"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Kudriavtsev, A.V., Vakhrusheva, A.V., Novoseletsky, V.N., Bozdaganyan, M.E., Shaitan, K.V., Kirpichnikov, M.P., and Sokolova, O.S. (2022). Immune Escape Associated with RBD Omicron Mutations and SARS-CoV-2 Evolution Dynamics. Viruses, 14.","DOI":"10.20944\/preprints202206.0022.v1"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1016\/j.ijbiomac.2022.07.254","article-title":"Omicron (B.1.1.529)\u2014A new heavily mutated variant: Mapped location and probable properties of its mutations with an emphasis on S-glycoprotein","volume":"219","author":"Chakraborty","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"100527","DOI":"10.1016\/j.xcrm.2022.100527","article-title":"Insights on the mutational landscape of the SARS-CoV-2 Omicron variant receptor-binding domain","volume":"3","author":"Miller","year":"2022","journal-title":"Cell Rep. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/S0006-3495(97)78756-3","article-title":"The statistical-thermodynamic basis for computation of binding affinities: A critical review","volume":"72","author":"Gilson","year":"1997","journal-title":"Biophys. J."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Owoloye, A.J., Ligali, F.C., Enejoh, O.A., Musa, A.Z., Aina, O., Idowu, E.T., and Oyebola, K.M. (2022). Molecular docking, simulation and binding free energy analysis of small molecules as PfHT1 inhibitors. PLoS ONE, 17.","DOI":"10.1101\/2022.04.27.489756"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s11030-020-10171-6","article-title":"Designing of peptide aptamer targeting the receptor-binding domain of spike protein of SARS-CoV-2: An in silico study","volume":"26","author":"Devi","year":"2022","journal-title":"Mol. Divers."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Halder, S., Thakur, A., Keshry, S.S., Jana, P., Karothia, D., Das Jana, I., Acevedo, O., Swain, R.K., Mondal, A., and Chattopadhyay, S. (2023). SELEX based aptamers with diagnostic and entry inhibitor therapeutic potential for SARS-CoV-2. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-41885-w"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3262","DOI":"10.1016\/j.sjbs.2021.02.066","article-title":"Screening of inhibitors against SARS-CoV-2 spike protein and their capability to block the viral entry mechanism: A viroinformatics study","volume":"28","author":"Farouk","year":"2021","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1002\/prot.26208","article-title":"Molecular dynamics analysis of a flexible loop at the binding interface of the SARS-CoV-2 spike protein receptor-binding domain","volume":"90","author":"Williams","year":"2022","journal-title":"Proteins Struct. Funct. Bioinform."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Khrenova, M., Nikiforova, L., Grabovenko, F., Orlova, N., Sinegubova, M., Kolesov, D., Zavyalova, E., Spiridonova, V., Zatsepin, T., and Zvereva, M. (2022). In vitro Selection of an Aptamer Targeting SARS-CoV-2 Spike Protein with Nanopore Sequence Identification Reveals Discrimination Between the Authentic Strain and Omicron. ChemRxiv.","DOI":"10.26434\/chemrxiv-2022-d9gcs"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Kumar, A., Sharma, M., Richardson, C.D., and Kelvin, D.J. (2022). Potential of Natural Alkaloids From Jadwar (Delphinium denudatum) as Inhibitors Against Main Protease of COVID-19: A Molecular Modeling Approach. Front. Mol. Biosci., 9.","DOI":"10.3389\/fmolb.2022.898874"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1002\/jcb.30397","article-title":"Drug repurposing for Mpox: Discovery of small molecules as potential inhibitors against DNA-dependent RNA polymerase using molecular modeling approach","volume":"124","author":"Dutt","year":"2023","journal-title":"J. Cell. Biochem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s43088-021-00152-5","article-title":"Search for RNA aptamers against non-structural protein of SARS-CoV-2: Design using molecular dynamics approach","volume":"10","author":"Kothandan","year":"2021","journal-title":"Beni-Suef Univ. J. Basic Appl. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Piplani, S., Singh, P.K., Winkler, D.A., and Petrovsky, N. (2021). Author Correction: In silico comparison of SARS-CoV-2 spike protein-ACE2 binding affinities across species and implications for virus origin. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-98366-1"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"9410","DOI":"10.1021\/ja980795y","article-title":"Small molecule binding to the mixed-valent Diiron center of methane monooxygenase hydroxylase from Methylococcus capsulatus (Bath) as revealed by ENDOR spectroscopy","volume":"120","author":"Willems","year":"1998","journal-title":"J. Am. Chem. Soc."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"10266","DOI":"10.1002\/anie.202100225","article-title":"Aptamer Blocking Strategy Inhibits SARS-CoV-2 Virus Infection","volume":"60","author":"Sun","year":"2021","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e2112942118","DOI":"10.1073\/pnas.2112942118","article-title":"A serum-stable RNA aptamer specific for SARS-CoV-2 neutralizes viral entry","volume":"118","author":"Valero","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Adachi, T., and Nakamura, Y. (2019). Aptamers: A review of their chemical properties and modifications for therapeutic application. Molecules, 24.","DOI":"10.3390\/molecules24234229"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/6\/805\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:45:34Z","timestamp":1760031934000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/6\/805"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,1]]},"references-count":65,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["biom15060805"],"URL":"https:\/\/doi.org\/10.3390\/biom15060805","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,1]]}}}