{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T05:54:22Z","timestamp":1783835662304,"version":"3.55.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,26]],"date-time":"2022-08-26T00:00:00Z","timestamp":1661472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>\n                    Despite what we know so far, Covid-19, caused by SARS-CoV-2 virus, remains a pandemic that still require urgent healthcare intervention. The frequent mutations of the SARS-CoV-2 virus has rendered disease control with vaccines and antiviral drugs quite challenging, with newer variants surfacing constantly. There is therefore the need for newer, effective and efficacious drugs against coronaviruses. Considering the central role of RNA dependent, RNA polymerase (RdRp) as an enzyme necessary for the virus life cycle and its conservation among coronaviruses, we investigated potential host miRNAs that can be employed as broad-range antiviral drugs averse to coronaviruses, with particular emphasis on BCoV, MERS-CoV, SARS-CoV and SARS-CoV-2. miRNAs are small molecules capable of binding mRNA and regulate expression at transcriptional or translational levels. Our hypothesis is that host miRNAs have the potential of blocking coronavirus replication through miRNA-RdRp mRNA interaction. To investigate this, we retrieved the open reading frame (ORF1ab) nucleotide sequences and used them to interrogate miRNA databases for miRNAs that can bind them. We employed various bioinformatics tools to predict and identify the most effective host miRNAs. In all, we found 27 miRNAs that target RdRp mRNA sequence of multiple coronaviruses, of which three - hsa-miR-1283, hsa-miR-579-3p, and hsa-miR-664b-3p target BCoV, SARS-CoV and SARS-CoV-2. Additionally, hsa-miR-374a-5p has three bovine miRNA homologs viz bta-miR-374a, bta-miR-374b, and bta-miR-374c. Inhibiting the expression of RdRp enzyme\n                    <jats:italic>via<\/jats:italic>\n                    non-coding RNA is novel and of great therapeutic importance in the control of coronavirus replication, and could serve as a broad-spectrum antiviral, with hsa-miR-1283, hsa-miR-579-3p, and hsa-miR-664b-3p as highly promising.\n                  <\/jats:p>","DOI":"10.3389\/fgene.2022.973252","type":"journal-article","created":{"date-parts":[[2022,8,26]],"date-time":"2022-08-26T05:20:15Z","timestamp":1661491215000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Deciphering inhibitory mechanism of coronavirus replication through host miRNAs-RNA-dependent RNA polymerase interactome"],"prefix":"10.3389","volume":"13","author":[{"given":"Olanrewaju B.","family":"Morenikeji","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muyiwa S.","family":"Adegbaju","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olayinka S.","family":"Okoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asegunloluwa E.","family":"Babalola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Grytsay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olubumi A.","family":"Braimah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mabel O.","family":"Akinyemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bolaji N.","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1186\/s12967-020-02439-0","article-title":"Analysis of SARS-CoV-2 RNA-dependent RNA polymerase as a potential therapeutic drug target using a computational approach","volume":"18","author":"Aftab","year":"2020","journal-title":"J. Transl. Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"5381","DOI":"10.1074\/jbc.M114.626325","article-title":"miR-28-3p is a cellular restriction factor that inhibits human T cell leukemia virus, type 1 (HTLV-1) replication and virus infection","volume":"290","author":"Bai","year":"2015","journal-title":"J. Biol. Chem."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1109\/TCBB.2017.2752703","article-title":"Mutli-features prediction of protein translational modification sites","volume":"15","author":"Bao","year":"2018","journal-title":"IEEE\/ACM Trans. Comput. Biol. Bioinform."},{"key":"B4","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1002\/jmv.25700","article-title":"Genomic variance of the 2019\u2010nCoV coronavirus","volume":"92","author":"Ceraolo","year":"2020","journal-title":"J. Med. Virol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e930552","DOI":"10.12659\/MSM.930552","article-title":"miR-1283 contributes to endoplasmic reticulum stress in the development of hypertension through the activating transcription factor-4 (ATF4)\/C\/EBP-Homologous protein (CHOP) signaling pathway","volume":"27","author":"Chen","year":"2021","journal-title":"Med. Sci. Monit."},{"key":"B6","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1080\/21505594.2020.1864136","article-title":"gga-miR-1603 and gga-miR-1794 directly target viral L gene and function as a broad-spectrum antiviral factor against NDV replication","volume":"12","author":"Chen","year":"2021","journal-title":"Virulence"},{"key":"B7","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1186\/1471-2148-10-210","article-title":"BMGE (block mapping and gathering with entropy): a new software for selection of phylogenetic informative regions from multiple sequence alignments","volume":"10","author":"Criscuolo","year":"2010","journal-title":"BMC Evol. Biol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"116958","DOI":"10.1016\/j.lfs.2019.116958","article-title":"Molecular dynamics and docking reveal the potency of novel GTP derivatives against RNA-dependent RNA polymerase of genotype 4a HCV","volume":"238","author":"Elfiky","year":"2019","journal-title":"Life Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1002\/jmv.24736","article-title":"Quantitative structure\u2010activity relationship and molecular docking revealed a potency of anti\u2010hepatitis C virus drugs against human corona viruses","volume":"89","author":"Elfiky","year":"2017","journal-title":"J. Med. Virol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"2044","DOI":"10.1002\/jmv.24678","article-title":"Zika viral polymerase inhibition using anti\u2010HCV drugs both in market and under clinical trials","volume":"88","author":"Elfiky","year":"2016","journal-title":"J. Med. Virol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1007\/s13337-019-00516-7","article-title":"Novel inhibitors against wild-type and mutated HCV NS3 serine protease: An in silico study","volume":"30","author":"Ezat","year":"2019","journal-title":"VirusDisease"},{"key":"B12","doi-asserted-by":"publisher","first-page":"E5005","DOI":"10.1073\/pnas.1607753113","article-title":"miR-579-3p controls melanoma progression and resistance to target therapy","volume":"113","author":"Fattore","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B13","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1126\/science.abb7498","article-title":"Structure of the RNA-dependent RNA polymerase from COVID-19 virus","volume":"368","author":"Gao","year":"2020","journal-title":"Science"},{"key":"B14","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1093\/sysbio\/syq010","article-title":"New algorithms and methods to estimate maximum-likelihood phylogenies: Assessing the performance of PhyML 3.0","volume":"59","author":"Guindon","year":"2010","journal-title":"Syst. Biol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"ra126","DOI":"10.1126\/scisignal.aab3183","article-title":"The microRNA miR-485 targets host and influenza virus transcripts to regulate antiviral immunity and restrict viral replication","volume":"8","author":"Ingle","year":"2015","journal-title":"Sci. Signal."},{"key":"B16","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.bbrc.2020.08.116","article-title":"RNA-dependent RNA polymerase: Structure, mechanism, and drug discovery for COVID-19","volume":"538","author":"Jiang","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B17","doi-asserted-by":"publisher","first-page":"16760","DOI":"10.1002\/jcb.28935","article-title":"The effect of miR\u2010579 on the PI3K\/AKT pathway in human glioblastoma PTEN mutant cell lines","volume":"120","author":"Kalhori","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1177\/1535370215589051","article-title":"Human miR-3145 inhibits influenza a viruses replication by targeting and silencing viral PB1 gene","volume":"240","author":"Khongnomnan","year":"2015","journal-title":"Exp. Biol. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2342","DOI":"10.1038\/s41467-019-10280-3","article-title":"Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors","volume":"10","author":"Kirchdoerfer","year":"2019","journal-title":"Nat. Commun."},{"key":"B20","doi-asserted-by":"publisher","first-page":"72","DOI":"10.12688\/f1000research.22211.2","article-title":"Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China","volume":"9","author":"Kruse","year":"2020","journal-title":"F1000Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1093\/molbev\/msy096","article-title":"Mega X: Molecular evolutionary genetics analysis across computing platforms","volume":"35","author":"Kumar","year":"2018","journal-title":"Mol. Biol. Evol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"147","DOI":"10.33963\/KP.15696","article-title":"MicroRNA 1283 alleviates cardiomyocyte damage caused by hypoxia\/reoxygenation via targeting GADD45A and inactivating the JNK and p38 MAPK signaling pathways","volume":"79","author":"Liu","year":"2021","journal-title":"Kardiol. Pol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2031","DOI":"10.3892\/or.2020.7771","article-title":"lncRNA RASSF8-AS1 suppresses the progression of laryngeal squamous cell carcinoma via targeting the miR-664b-3p\/TLE1 axis","volume":"44","author":"Liu","year":"2020","journal-title":"Oncol. Rep."},{"key":"B24","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/S0140-6736(20)30251-8","article-title":"Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding.","volume":"395","author":"Lu","year":"2020","journal-title":"Lancet"},{"key":"B25","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1128\/AAC.44.4.859-866.2000","article-title":"Broad-spectrum antiviral activity of the IMP dehydrogenase inhibitor VX-497: A comparison with ribavirin and demonstration of antiviral additivity with alpha interferon","volume":"44","author":"Markland","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2020.582953","article-title":"Evolutionarily conserved long non-coding RNA regulates gene expression in cytokine storm during COVID-19","volume":"8","author":"Morenikeji","year":"2021","journal-title":"Front. Bioeng. Biotechnol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"584392","DOI":"10.3389\/fgene.2020.584392","article-title":"Integrative network analysis of predicted miRNA-targets regulating expression of immune response genes in bovine coronavirus infection.","volume":"11","author":"Morenikeji","year":"2020","journal-title":"Front. Genet."},{"key":"B28","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1016\/j.molcel.2009.06.003","article-title":"Cellular microRNA and P bodies modulate host-HIV-1 interactions","volume":"34","author":"Nathans","year":"2009","journal-title":"Mol. Cell"},{"key":"B29","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1038\/s41422-020-0290-0","article-title":"Virus against virus: a potential treatment for 2019-nCov (SARS-CoV-2) and other RNA viruses","volume":"30","author":"Nguyen","year":"2020","journal-title":"Cell Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"634047","DOI":"10.3389\/fphar.2021.634047","article-title":"Discovering potential RNA dependent RNA polymerase inhibitors as prospective drugs against COVID-19: an in silico approach","volume":"12","author":"Saha","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1038\/nrmicro2971","article-title":"RNA viruses and the host microRNA machinery","volume":"11","author":"tenOever","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.molmed.2016.11.003","article-title":"MicroRNA regulation of RNA virus replication and pathogenesis","volume":"23","author":"Trobaugh","year":"2017","journal-title":"Trends Mol. Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"21899","DOI":"10.1038\/s41598-021-01280-9","article-title":"Regulatory network of miRNA, lncRNA, transcription factor and target immune response genes in bovine mastitis","volume":"11","author":"Tucker","year":"2021","journal-title":"Sci. Rep."},{"key":"B34","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.cell.2020.02.058","article-title":"Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein","volume":"181","author":"Walls","year":"2020","journal-title":"Cell"},{"key":"B35","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/s41422-020-0282-0","article-title":"Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro","volume":"30","author":"Wang","year":"2020","journal-title":"Cell Res."},{"key":"B36","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.antiviral.2013.08.001","article-title":"Overexpression of microRNA gga-miR-21 in chicken fibroblasts suppresses replication of infectious bursal disease virus through inhibiting VP1 translation","volume":"100","author":"Wang","year":"2013","journal-title":"Antivir. Res."},{"key":"B37","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.chom.2020.02.001","article-title":"Genome composition and divergence of the novel coronavirus (2019-nCoV) originating in China","volume":"27","author":"Wu","year":"2020","journal-title":"Cell Host Microbe"},{"key":"B38","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1016\/j.coviro.2011.10.019","article-title":"Anti-HCV drugs in the pipeline","volume":"1","author":"Yang","year":"2011","journal-title":"Curr. Opin. Virol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"5645","DOI":"10.1128\/JVI.02655-12","article-title":"Human microRNA hsa-miR-296-5p suppresses enterovirus 71 replication by targeting the viral genome","volume":"87","author":"Zheng","year":"2013","journal-title":"J. Virol."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.973252\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,26]],"date-time":"2022-08-26T05:20:17Z","timestamp":1661491217000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.973252\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,26]]},"references-count":39,"alternative-id":["10.3389\/fgene.2022.973252"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2022.973252","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.06.18.496304","asserted-by":"object"}]},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,26]]},"article-number":"973252"}}