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Here, we synthesized and studied the antiviral properties of a novel nitrocatechol compound (1c) and other analogs that are structurally related to the catechol derivative dynasore. Interestingly, compound 1c strongly inhibited two DEDD box viral ribonucleases, HIV-1 RNase H and SARS-CoV-2 nsp14 3\u2032-to-5\u2032 exoribonuclease (ExoN). While 1c inhibited SARS-CoV-2 ExoN activity, it did not interfere with the mRNA methyltransferase activity of nsp14. In silico molecular docking placed compound 1c in the catalytic pocket of the ExoN domain of nsp14. Finally, 1c inhibited SARS-CoV-2 replication but had no toxicity to human lung adenocarcinoma cells. Given its simple chemical synthesis from easily available starting materials, these results suggest that 1c might be a lead compound for the design of new antiviral compounds that target coronavirus nsp14 ExoN and other viral ribonucleases.<\/jats:p>","DOI":"10.3390\/v15071539","type":"journal-article","created":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T01:43:22Z","timestamp":1689212602000},"page":"1539","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Analogs of the Catechol Derivative Dynasore Inhibit HIV-1 Ribonuclease H, SARS-CoV-2 nsp14 Exoribonuclease, and Virus Replication"],"prefix":"10.3390","volume":"15","author":[{"given":"Abhishek","family":"Asthana","sequence":"first","affiliation":[{"name":"Cancer Biology, Lerner Research Institute, Cleveland Clinic, 2111 East 96th St, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6630-8636","authenticated-orcid":false,"given":"Angela","family":"Corona","sequence":"additional","affiliation":[{"name":"Laboratorio di Virologia Molecolare, Dipartimento di Scienze della Vita e Dell\u2019Ambiente, Universit\u00e1 degli Studi di Cagliari, Cittadella Universitaria di Monserrato SS554, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo-Jin","family":"Shin","sequence":"additional","affiliation":[{"name":"Cancer Biology, Lerner Research Institute, Cleveland Clinic, 2111 East 96th St, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi-Jeong","family":"Kwak","sequence":"additional","affiliation":[{"name":"Cancer Biology, Lerner Research Institute, Cleveland Clinic, 2111 East 96th St, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0869-9026","authenticated-orcid":false,"given":"Christina","family":"Gaughan","sequence":"additional","affiliation":[{"name":"Cancer Biology, Lerner Research Institute, Cleveland Clinic, 2111 East 96th St, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4849-0980","authenticated-orcid":false,"given":"Enzo","family":"Tramontano","sequence":"additional","affiliation":[{"name":"Laboratorio di Virologia Molecolare, Dipartimento di Scienze della Vita e Dell\u2019Ambiente, Universit\u00e1 degli Studi di Cagliari, Cittadella Universitaria di Monserrato SS554, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae U.","family":"Jung","sequence":"additional","affiliation":[{"name":"Cancer Biology, Lerner Research Institute, Cleveland Clinic, 2111 East 96th St, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8413-4342","authenticated-orcid":false,"given":"Rainer","family":"Schobert","sequence":"additional","affiliation":[{"name":"Organic Chemistry 1, University of Bayreuth, Universit\u00e4tsstrasse 30, 95440 Bayreuth, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7660-5255","authenticated-orcid":false,"given":"Babal Kant","family":"Jha","sequence":"additional","affiliation":[{"name":"Center for Immunotherapy and Precision Immuno-Oncology, Lerner Research Institute and Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, 2111 East 96th St, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Silverman","sequence":"additional","affiliation":[{"name":"Cancer Biology, Lerner Research Institute, Cleveland Clinic, 2111 East 96th St, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7305-346X","authenticated-orcid":false,"given":"Bernhard","family":"Biersack","sequence":"additional","affiliation":[{"name":"Organic Chemistry 1, University of Bayreuth, Universit\u00e4tsstrasse 30, 95440 Bayreuth, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/s41392-020-0190-2","article-title":"Overview of lethal human coronaviruses","volume":"5","author":"Chen","year":"2020","journal-title":"Signal Transduct. 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