{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:16:56Z","timestamp":1767831416518,"version":"3.49.0"},"reference-count":57,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T00:00:00Z","timestamp":1638230400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005375","name":"Latvian Council of Science","doi-asserted-by":"publisher","award":["VPP-COVID-2020\/1-0014"],"award-info":[{"award-number":["VPP-COVID-2020\/1-0014"]}],"id":[{"id":"10.13039\/501100005375","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["1.1.1.2\/VIAA\/2\/18\/379"],"award-info":[{"award-number":["1.1.1.2\/VIAA\/2\/18\/379"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses mRNA capping to evade the human immune system. The cap formation is performed by the SARS-CoV-2 mRNA cap methyltransferases (MTases) nsp14 and nsp16, which are emerging targets for the development of broad-spectrum antiviral agents. Here, we report results from high-throughput virtual screening against these two enzymes. The docking of seven million commercially available drug-like compounds and S-adenosylmethionine (SAM) co-substrate analogues against both MTases resulted in 80 virtual screening hits (39 against nsp14 and 41 against nsp16), which were purchased and tested using an enzymatic homogeneous time-resolved fluorescent energy transfer (HTRF) assay. Nine compounds showed micromolar inhibition activity (IC50 &lt; 200 \u03bcM). The selectivity of the identified inhibitors was evaluated by cross-checking their activity against human glycine N-methyltransferase. The majority of the compounds showed poor selectivity for a specific MTase, no cytotoxic effects, and rather poor cell permeability. Nevertheless, the identified compounds represent good starting points that have the potential to be developed into efficient viral MTase inhibitors.<\/jats:p>","DOI":"10.3390\/ph14121243","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T23:22:56Z","timestamp":1638314576000},"page":"1243","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Discovery of SARS-CoV-2 Nsp14 and Nsp16 Methyltransferase Inhibitors by High-Throughput Virtual Screening"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0221-8658","authenticated-orcid":false,"given":"Raitis","family":"Bobrovs","sequence":"first","affiliation":[{"name":"Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iveta","family":"Kanepe","sequence":"additional","affiliation":[{"name":"Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nauris","family":"Narvaiss","sequence":"additional","affiliation":[{"name":"Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liene","family":"Patetko","sequence":"additional","affiliation":[{"name":"Faculty of Biology, University of Latvia, Jelgavas 1, LV-1004 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gints","family":"Kalnins","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Centre, Ratsupites 1 k1, LV-1067 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihails","family":"Sisovs","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Centre, Ratsupites 1 k1, LV-1067 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna L.","family":"Bula","sequence":"additional","affiliation":[{"name":"Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Solveiga","family":"Grinberga","sequence":"additional","affiliation":[{"name":"Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martins","family":"Boroduskis","sequence":"additional","affiliation":[{"name":"Faculty of Biology, University of Latvia, Jelgavas 1, LV-1004 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0097-0931","authenticated-orcid":false,"given":"Anna","family":"Ramata-Stunda","sequence":"additional","affiliation":[{"name":"Faculty of Biology, University of Latvia, Jelgavas 1, LV-1004 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4047-2438","authenticated-orcid":false,"given":"Nils","family":"Rostoks","sequence":"additional","affiliation":[{"name":"Faculty of Biology, University of Latvia, Jelgavas 1, LV-1004 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aigars","family":"Jirgensons","sequence":"additional","affiliation":[{"name":"Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaspars","family":"Tars","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Centre, Ratsupites 1 k1, LV-1067 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3922-2447","authenticated-orcid":false,"given":"Kristaps","family":"Jaudzems","sequence":"additional","affiliation":[{"name":"Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nrmicro.2016.81","article-title":"SARS and MERS: Recent insights into emerging coronaviruses","volume":"14","author":"Falzarano","year":"2016","journal-title":"Nat. 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