{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T21:19:37Z","timestamp":1789507177588,"version":"build-2803163510"},"reference-count":23,"publisher":"MDPI AG","issue":"3","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":[{"name":"Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro\u2014FAPERJ","award":["CNE E-26\/200.314\/2022-260923"],"award-info":[{"award-number":["CNE E-26\/200.314\/2022-260923"]}]},{"name":"Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro\u2014FAPERJ","award":["E-26\/200.314\/2025"],"award-info":[{"award-number":["E-26\/200.314\/2025"]}]},{"name":"Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro\u2014FAPERJ","award":["JCNE E-26\/201.230\/2022"],"award-info":[{"award-number":["JCNE E-26\/201.230\/2022"]}]},{"name":"Fiocruz Inova COVID-19\u2014Gera\u00e7\u00e3o de Conhecimento","award":["VPPCB-005-FIO-20-2-49"],"award-info":[{"award-number":["VPPCB-005-FIO-20-2-49"]}]},{"name":"Fiocruz-Institut Pasteur-USP"},{"DOI":"10.13039\/501100003593","name":"Brazilian National Council for Scientific and Technological Development-CNPq: \u2018Productivity Fellowship\u2019","doi-asserted-by":"publisher","award":["316462\/2021-7"],"award-info":[{"award-number":["316462\/2021-7"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Brazilian National Council for Scientific and Technological Development-CNPq: \u2018Productivity Fellowship\u2019","doi-asserted-by":"publisher","award":["307891\/2025-9"],"award-info":[{"award-number":["307891\/2025-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Brazilian National Council for Scientific and Technological Development-CNPq: \u2018Productivity Fellowship\u2019","doi-asserted-by":"publisher","award":["304797\/2022-7"],"award-info":[{"award-number":["304797\/2022-7"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006506","name":"Brazilian Ministry of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006506","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Prior molecular docking and dynamics studies indicated a pyrazolopyridine\u2013sulfonamide derivative (L87\/PPS2, or simply PPS2) as a potential interactant with SARS-CoV-2 protein targets. The in vitro anti-SARS-CoV-2 activity and cytotoxicity profile of PPS2 were screened alongside a series of pyrazolopyrimidine (PZP) and triazolopyrimidine (TZP) derivatives. PPS2 demonstrated only partial inhibition of SARS-CoV-2 growth in Vero E6 cells at 100 \u00b5M. Crucially, however, four out of five PZPs and eight out of fourteen TZPs exhibited potent in vitro inhibitory activity against SARS-CoV-2 at 100 \u00b5M, with none of the tested compounds displaying cytotoxicity against Vero E6 cells at this concentration. Further characterization of one compound, PZP25, revealed an inhibitory concentration (IC50) of 8.2 \u00b5M, combined with low cytotoxicity (CC50 &gt; 800 \u00b5M), yielding a selectivity index greater than 100. Time of addition assays indicated that PZP25\u2019s antiviral effects were most pronounced when administered post-infection. While cellular pre-treatment provided a partial reduction in virus growth, modest virucidal activity was also observed at warmer temperatures (20 \u00b0C and 37 \u00b0C). Collectively, our findings demonstrate that PZP and TZP derivatives possess potent inhibitory activity of SARS-CoV-2 replication in vitro and highlight such compounds as promising chemical scaffolds for the development of novel antiviral agents targeting coronaviruses.<\/jats:p>","DOI":"10.3390\/pathogens15030324","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T14:14:05Z","timestamp":1773843245000},"page":"324","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Antiviral Activity of Pyrazolopyrimidine and Triazolopyrimidine Derivatives Against SARS-CoV-2 In Vitro: Identifying PZP25 as a Promising Scaffold"],"prefix":"10.3390","volume":"15","author":[{"given":"Saiqa","family":"Sardar","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de V\u00edrus Respirat\u00f3rios, Exantem\u00e1ticos, Enterov\u00edrus e Emerg\u00eancias Virais, Instituto Oswaldo Cruz (IOC-Fiocruz), Rio de Janeiro 21040-360, RJ, Brazil"},{"name":"Laborat\u00f3rio de Pesquisa em Mal\u00e1ria, Instituto Oswaldo Cruz (IOC-Fiocruz), Rio de Janeiro 21045-900, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1689-3731","authenticated-orcid":false,"given":"Jessica S. C. C.","family":"Martins","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de V\u00edrus Respirat\u00f3rios, Exantem\u00e1ticos, Enterov\u00edrus e Emerg\u00eancias Virais, Instituto Oswaldo Cruz (IOC-Fiocruz), Rio de Janeiro 21040-360, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9796-1494","authenticated-orcid":false,"given":"Thiago C.","family":"Sousa","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de V\u00edrus Respirat\u00f3rios, Exantem\u00e1ticos, Enterov\u00edrus e Emerg\u00eancias Virais, Instituto Oswaldo Cruz (IOC-Fiocruz), Rio de Janeiro 21040-360, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5915-0888","authenticated-orcid":false,"given":"Andreon S. M.","family":"Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Desenvolvimento Tecnol\u00f3gico em Virologia, Instituto Oswaldo Cruz (IOC-Fiocruz), Rio de Janeiro 21040-360, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3462-7277","authenticated-orcid":false,"given":"Marcelo A.","family":"Pinto","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Desenvolvimento Tecnol\u00f3gico em Virologia, Instituto Oswaldo Cruz (IOC-Fiocruz), Rio de Janeiro 21040-360, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8123-042X","authenticated-orcid":false,"given":"Fl\u00e1via F.","family":"Silveira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de S\u00edntese de F\u00e1rmacos, Instituto de Tecnologia em F\u00e1rmacos (Farmanguinhos-Fiocruz), Rio de Janeiro 21041-250, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thais B.","family":"Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de S\u00edntese de F\u00e1rmacos, Instituto de Tecnologia em F\u00e1rmacos (Farmanguinhos-Fiocruz), Rio de Janeiro 21041-250, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9069-8016","authenticated-orcid":false,"given":"Rodolfo R. 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