{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:22:49Z","timestamp":1781104969862,"version":"3.54.1"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"12","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Shandong Provincial Natural Science Foundation","doi-asserted-by":"crossref","award":["ZR2023QH546"],"award-info":[{"award-number":["ZR2023QH546"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007129","name":"Shandong Provincial Natural Science Foundation","doi-asserted-by":"crossref","award":["ZR2023QH494"],"award-info":[{"award-number":["ZR2023QH494"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007129","name":"Shandong Provincial Natural Science Foundation","doi-asserted-by":"crossref","award":["ZR2023LZY003"],"award-info":[{"award-number":["ZR2023LZY003"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Jinan Microecological Biomedicine Shandong Laboratory","award":["JNL-2022004Q"],"award-info":[{"award-number":["JNL-2022004Q"]}]},{"name":"Jinan Microecological Biomedicine Shandong Laboratory","award":["JNL-2025005B"],"award-info":[{"award-number":["JNL-2025005B"]}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2023YFC2506004"],"award-info":[{"award-number":["2023YFC2506004"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Zhejiang Provincial Applied Basic Research (Leading Goose) Program","award":["2024C03218"],"award-info":[{"award-number":["2024C03218"]}]},{"DOI":"10.13039\/100012905","name":"Department of Science and Technology of Shandong Province","doi-asserted-by":"publisher","award":["SYS202202"],"award-info":[{"award-number":["SYS202202"]}],"id":[{"id":"10.13039\/100012905","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,3,24]]},"abstract":"<jats:p>\n                    Innate immune evasion is critical for productive viral replication. Activation of the cGAS\u2013STING antiviral signaling pathway and its downstream effector genes plays a pivotal role in restricting viral replication during early DNA virus infection. Through a comprehensive genomic screen of monkeypox virus (MPXV), we identified three viral genes, OPG147, OPG188, and OPG200, whose expression potently suppresses cGAS\u2013STING pathway activation. Notably, the N-terminal domain of the Poxin protein encoded by OPG188 exhibits nuclease activity and cleaves the cyclic dinucleotide second messenger 2\u20323\u2032-cGAMP. Using site-directed mutagenesis, we further delineated nine conserved regions and four key amino acid residues\u2014H15, K140, R182, and I79\u2014within Poxin that are essential for antagonism of cGAS\u2013STING signaling. Moreover, via molecular docking and high-throughput screening of 7,155 small molecules targeting the catalytic pocket of Poxin, we identified two compounds that competitively bind to Poxin, inhibiting its cGAMP\u2014degrading activity and consequently restoring cGAS\u2013STING-mediated antiviral signaling upon MPXV infection. Collectively, these findings underscore the pivotal role of OPG188 in modulating antiviral immune responses and highlight NAD\n                    <jats:sup>+<\/jats:sup>\n                    and Theaflavin-3\u2019-gallate as promising candidates for the development of anti-MPXV therapeutics.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2523334123","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T17:40:47Z","timestamp":1773855647000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["Monkeypox virus protein OPG188 antagonizes cGAS\u2013STING antiviral signaling pathway to mediate immune evasion"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9937-2645","authenticated-orcid":false,"given":"Zhaoyi","family":"Pan","sequence":"first","affiliation":[{"name":"Jinan Microecological Biomedicine Shandong Laboratory","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jinan Microecological Biomedicine Shandong Laboratory","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianbo","family":"Geng","sequence":"additional","affiliation":[{"name":"Jinan Microecological Biomedicine Shandong Laboratory","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Wang","sequence":"additional","affiliation":[{"name":"Jinan Microecological Biomedicine Shandong Laboratory","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7902-0893","authenticated-orcid":false,"given":"Lijiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of High-level Biosafety and Biomedical Transformation, Hangzhou Medical College","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luyao","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of High-level Biosafety and Biomedical Transformation, Hangzhou Medical College","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhong","family":"Yin","sequence":"additional","affiliation":[{"name":"Infectious Disease Control Institute, Shandong Center for Disease Control and Prevention","place":["Jinan, China"]},{"name":"Shandong Provincial Key Laboratory of Intelligent Monitoring, Early Warning, Prevention and Control for Infectious Diseases","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jinan Microecological Biomedicine Shandong Laboratory","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujun","family":"Liu","sequence":"additional","affiliation":[{"name":"Jinan Microecological Biomedicine Shandong Laboratory","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jinan Microecological Biomedicine Shandong Laboratory","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Fan","sequence":"additional","affiliation":[{"name":"Jinan Microecological Biomedicine Shandong Laboratory","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangjian","family":"Xue","sequence":"additional","affiliation":[{"name":"Jinan Microecological Biomedicine Shandong Laboratory","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Li","sequence":"additional","affiliation":[{"name":"Jinan Microecological Biomedicine Shandong Laboratory","place":["Jinan, China"]},{"name":"Shandong First Medical University and Shandong Academy of Medical Sciences","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianle","family":"Li","sequence":"additional","affiliation":[{"name":"Jinan Microecological Biomedicine Shandong Laboratory","place":["Jinan, China"]},{"name":"Shandong First Medical University and Shandong Academy of Medical Sciences","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yating","family":"Yu","sequence":"additional","affiliation":[{"name":"Jinan Microecological Biomedicine Shandong Laboratory","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hangping","family":"Yao","sequence":"additional","affiliation":[{"name":"Jinan Microecological Biomedicine Shandong Laboratory","place":["Jinan, China"]},{"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changzhong","family":"Jin","sequence":"additional","affiliation":[{"name":"Jinan Microecological Biomedicine Shandong Laboratory","place":["Jinan, China"]},{"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8804-552X","authenticated-orcid":false,"given":"Nanping","family":"Wu","sequence":"additional","affiliation":[{"name":"Jinan Microecological Biomedicine Shandong Laboratory","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.21091"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2022.4567"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(22)00869-6"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.ade6360"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-0244-x"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.05.013"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3558"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2002521"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0928-6"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34761-0"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.59753"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abb4565"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2025.2477639"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2022.2032928"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.03.017"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1012136"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.08.014"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.01.010"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1013198"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13348"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112306"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114122"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adf5808"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108044"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00577-23"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004783"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2014.09.006"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-7843.2008.00232.x"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202113943"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06423-8"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-023-00761-7"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2016.06"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.01578-22"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2020.113831"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38514-5"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.05.038"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2024.2372344"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002083"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002247"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002430"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01648-18"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.9.6479-6485.1996"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-78-3-677"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-023-01280-z"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2523334123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T17:41:58Z","timestamp":1773855718000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2523334123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,18]]},"references-count":44,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2026,3,24]]}},"alternative-id":["10.1073\/pnas.2523334123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2523334123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,18]]},"assertion":[{"value":"2025-08-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2523334123"}}