{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T07:00:05Z","timestamp":1786777205054,"version":"build-2736575974"},"reference-count":57,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,9]],"date-time":"2021-10-09T00:00:00Z","timestamp":1633737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UHK","award":["VT2019-2021"],"award-info":[{"award-number":["VT2019-2021"]}]},{"name":"Brazilian agencies Conselho Nacional de Pesquisa (CNPq)","award":["308225\/2018\u20130"],"award-info":[{"award-number":["308225\/2018\u20130"]}]},{"name":"Funda\u00e7\u00e3o de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ)","award":["E-02\/202.961\/2017"],"award-info":[{"award-number":["E-02\/202.961\/2017"]}]},{"name":"Ministry of Health of the Czech Republic","award":["FN HK 00179906"],"award-info":[{"award-number":["FN HK 00179906"]}]},{"name":"Charles University in Prague, Czech Republic","award":["PROGRES Q40"],"award-info":[{"award-number":["PROGRES Q40"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Continuing the work developed by our research group, in the present manuscript, we performed a theoretical study of 10 new structures derived from the antivirals cidofovir and ribavirin, as inhibitor prototypes for the enzyme thymidylate kinase from Variola virus (VarTMPK). The proposed structures were subjected to docking calculations, molecular dynamics simulations, and free energy calculations, using the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method, inside the active sites of VarTMPK and human TMPK (HssTMPK). The docking and molecular dynamic studies pointed to structures 2, 3, 4, 6, and 9 as more selective towards VarTMPK. In addition, the free energy data calculated through the MM-PBSA method, corroborated these results. This suggests that these compounds are potential selective inhibitors of VarTMPK and, thus, can be considered as template molecules to be synthesized and experimentally evaluated against smallpox.<\/jats:p>","DOI":"10.3390\/ph14101027","type":"journal-article","created":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T21:37:29Z","timestamp":1633901849000},"page":"1027","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["In Silico Studies of Potential Selective Inhibitors of Thymidylate Kinase from Variola virus"],"prefix":"10.3390","volume":"14","author":[{"given":"Danielle R.","family":"Garcia","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Modeling Applied to Chemical and Biological Defense, Military Institute of Engineering, Pra\u00e7a General Tiburcio 80, Urca, Rio de Janeiro 22290-270, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7410-5188","authenticated-orcid":false,"given":"Felipe R.","family":"Souza","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Pontifical Catholic University of Rio de Janeiro, Rio de Janeiro 22541-041, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana P.","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Federal University of Vi\u00e7osa, Avenida P. H. Rolfs, s\/n, Centro, Vi\u00e7osa 36570-000, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Valis","sequence":"additional","affiliation":[{"name":"Department of Neurology of the Medical Faculty of Charles University and University Hospital in Hradec Kralove, Sokolska 581, 50005 Hradec Kralove, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1772-8781","authenticated-orcid":false,"given":"Zby\u0161ek","family":"Pavelek","sequence":"additional","affiliation":[{"name":"Department of Neurology of the Medical Faculty of Charles University and University Hospital in Hradec Kralove, Sokolska 581, 50005 Hradec Kralove, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9664-1109","authenticated-orcid":false,"given":"Kamil","family":"Kuca","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanskeho 62, 50003 Hradec Kralove, Czech Republic"},{"name":"Biomedical Research Center, University Hospital in Hradec Kralove, Sokolska 581, 50005 Hradec Kralove, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7324-1353","authenticated-orcid":false,"given":"Teodorico C.","family":"Ramalho","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanskeho 62, 50003 Hradec Kralove, Czech Republic"},{"name":"Laboratory of Computational Chemistry, Department of Chemistry, UFLA, Lavras 37200-000, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6048-8103","authenticated-orcid":false,"given":"Tanos C. C.","family":"Fran\u00e7a","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Modeling Applied to Chemical and Biological Defense, Military Institute of Engineering, Pra\u00e7a General Tiburcio 80, Urca, Rio de Janeiro 22290-270, Brazil"},{"name":"Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanskeho 62, 50003 Hradec Kralove, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.vaccine.2019.10.049","article-title":"Co-administration of tecovirimat and ACAM2000\u2122 in non-human primates: Effect of tecovirimat treatment on ACAM2000 immunogenicity and efficacy versus lethal monkeypox virus challenge","volume":"38","author":"Russo","year":"2020","journal-title":"Vaccine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e221","DOI":"10.1016\/S1473-3099(18)30788-6","article-title":"Assessing a drug for an eradicated human disease: US Food and Drug Administration review of tecovirimat for the treatment of smallpox","volume":"19","author":"Harrington","year":"2019","journal-title":"Lancet Infect. 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