{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:42:48Z","timestamp":1792802568330,"version":"4.5.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T00:00:00Z","timestamp":1651190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Human enterovirus infections are mostly asymptomatic and occasionally could be severe and life-threatening. The conserved non-structural 2C from enteroviruses protein is a promising target in antiviral therapies against human enteroviruses. Understanding of 2C-drug interactions is crucial for developing the potential antiviral agents. While functions of enterovirus 2C proteins have been widely studied, three-dimensional structure information of 2C is limited. In this study, the structures of 2C proteins from 20 enteroviruses were simulated and reconstructed using <jats:italic>I-TASSER<\/jats:italic> programs. Subsequent docking studies of the known 22 antiviral inhibitors for 2C proteins were performed to uncover the inhibitor-binding characteristics of 2C. Among the potential inhibitors, the compound hydantoin exhibited the highest broad-spectrum antiviral activities with binding to 2C protein. The anti-enteroviral activity of GuaHCL, compound 19b, R523062, compound 12a, compound 12b, quinoline analogs 12a, compound 19d, N<jats:sup>6<\/jats:sup>-benzyladenosine, dibucaine derivatives 6i, TBZE-029, fluoxetine analogs 2b, dibucaine, 2-(\u03b1-hydroxybenzyl)-benzimidazole (HBB), metrifudil, pirlindole, MRL-1237, quinoline analogs 10a, zuclopenthixol, fluoxetine, fluoxetine HCl, and quinoline analogs 12c showed a trend of gradual decrease. In addition, the free energy with 22 compounds binding to EV 2C ranged from \u22120.35 to \u221288.18 kcal\/mol. Our <jats:italic>in silico<\/jats:italic> studies will provide important information for the development of pan-enterovirus antiviral agents based on 2C.<\/jats:p>","DOI":"10.3389\/fmicb.2022.856574","type":"journal-article","created":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T07:09:06Z","timestamp":1651216146000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Structure Prediction and Potential Inhibitors Docking of Enterovirus 2C Proteins"],"prefix":"10.3389","volume":"13","author":[{"given":"Daoqun","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leiliang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2518","DOI":"10.1099\/vir.0.2008\/002915-0","article-title":"Characterization of pharmacologically active compounds that inhibit poliovirus and enterovirus 71 infectivity","volume":"89","author":"Arita","year":"2008","journal-title":"J. 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