{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T09:41:50Z","timestamp":1774690910628,"version":"3.50.1"},"reference-count":58,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T00:00:00Z","timestamp":1702339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T00:00:00Z","timestamp":1702339200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2023,12,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The monkeypox virus (MPX) belongs to the\n            <jats:italic>Orthopoxvirus<\/jats:italic>\n            genus of the Poxviridae family, is endemic in parts of Africa and causes a disease in humans similar to smallpox. The most recent outbreak of MPX is already affecting 110 countries, with 86,956 confirmed cases since May 2022 and has consequently become a focus of interest. In particular, a molecular understanding of the virus is essential to study infection processes and pathogen-host interactions, predict tropism changes, or guide drug development and drug discovery as well as vaccine development or vaccine adaptation at a very early stage. Herein, we present a study of the structural proteome of the currently circulating MPX: Our consensus analysis of 3,713 genome sequences sampled within a year after the outbreak revealed 10,580 characteristic candidate open reading frames (ORFs). A search in the non-redundant protein database reduced the number of suspected ORFs to 1,079, of which 210 are representative proteins in typical MPX reference genomes. This should serve as a collection of putative proteins within the currently spreading MPX, a compound of information that could support timely drug discovery, mutational analyses, and vaccine development. We, herein, present the so far most comprehensive structural proteome by providing atomistic 3D models of 210 proteins, generated with three state-of-the-art structure prediction methods, including a mutational analysis of the proteome, with a particular focus on the drug-binding sites of tecovirimat and brincidofovir.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>The 2022 outbreak of the monkeypox virus already involves, by April 2023, 110 countries with 86,956 confirmed cases and 119 deaths. Understanding an emerging disease on a molecular level is essential to study infection processes and eventually guide drug discovery at an early stage. To support this, we provide the so far most comprehensive structural proteome of the monkeypox virus, which includes 210 structural models, each computed with three state-of-the-art structure prediction methods. Instead of building on a single-genome sequence, we generated our models from a consensus of 3,713 high-quality genome sequences sampled from patients within 1 year of the outbreak. Therefore, we present an average structural proteome of the currently isolated viruses, including mutational analyses with a special focus on drug-binding sites. Continuing dynamic mutation monitoring within the structural proteome presented here is essential to timely predict possible physiological changes in the evolving virus.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.02315-23","type":"journal-article","created":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T13:00:50Z","timestamp":1698152450000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["AI-assisted structural consensus-proteome prediction of human monkeypox viruses isolated within a year after the 2022 multi-country outbreak"],"prefix":"10.1128","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2151-0865","authenticated-orcid":false,"given":"Lena","family":"Parigger","sequence":"first","affiliation":[{"name":"Innophore , Graz, Austria"},{"name":"Institute of Molecular Biosciences, University of Graz , Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Krassnigg","sequence":"additional","affiliation":[{"name":"Innophore , Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9303-2981","authenticated-orcid":false,"given":"Stefan","family":"Grabuschnig","sequence":"additional","affiliation":[{"name":"Innophore , Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3485-9740","authenticated-orcid":false,"given":"Karl","family":"Gruber","sequence":"additional","affiliation":[{"name":"Innophore , Graz, Austria"},{"name":"Institute of Molecular Biosciences, University of Graz , Graz, Austria"},{"name":"Austrian Centre of Industrial Biotechnology , Graz, Austria"},{"name":"Field of Excellence BioHealth, University of Graz , Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7565-8868","authenticated-orcid":false,"given":"Georg","family":"Steinkellner","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biosciences, University of Graz , Graz, Austria"},{"name":"Field of Excellence BioHealth, University of Graz , Graz, Austria"},{"name":"Innophore , San Francisco, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0214-449X","authenticated-orcid":true,"given":"Christian C.","family":"Gruber","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biosciences, University of Graz , Graz, Austria"},{"name":"Austrian Centre of Industrial Biotechnology , Graz, Austria"},{"name":"Field of Excellence BioHealth, University of Graz , Graz, Austria"},{"name":"Innophore , San Francisco, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","first-page":"3686","article-title":"The Reinfection of Indonesia with Smallpox","volume":"44","author":"Gispen R","year":"1949","unstructured":"Gispen R . 1949. The Reinfection of Indonesia with Smallpox. Ned T Geneesk 44:3686\u20133695.","journal-title":"Ned T Geneesk"},{"key":"e_1_3_4_3_2","first-page":"277","article-title":"Smallpox and Monkeypox in non-human primates","volume":"39","author":"Arita I","year":"1968","unstructured":"Arita I , Henderson DA . 1968. Smallpox and Monkeypox in non-human primates. Bull World Health Organ 39:277\u2013283.","journal-title":"Bull World Health Organ"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1699-0463.1959.tb00328.x"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0014-5793(01)03144-1"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2002.1446"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00691.x"},{"key":"e_1_3_4_8_2","volume-title":"Human monkeypox","author":"Je\u017eek Z","year":"1988","unstructured":"Je\u017eek Z , Fenner F . 1988. Human monkeypox. Karger."},{"key":"e_1_3_4_9_2","first-page":"747","article-title":"Monkeypox virus: ecology and public health significance","volume":"66","author":"Khodakevich L","year":"1988","unstructured":"Khodakevich L , Jezek Z , Messinger D . 1988. Monkeypox virus: ecology and public health significance. Bull World Health Organ 66:747\u2013752.","journal-title":"Bull World Health Organ"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.04.014"},{"key":"e_1_3_4_11_2","first-page":"599","article-title":"Isolation and properties of the causal agent of a new variola-like disease (monkeypox) in man","volume":"46","author":"Marennikova SS","year":"1972","unstructured":"Marennikova SS , Seluhina EM , Mal\u2019ceva NN , Cimiskjan KL , Macevic GR . 1972. Isolation and properties of the causal agent of a new variola-like disease (monkeypox) in man. 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