{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:42:23Z","timestamp":1760146943799,"version":"build-2065373602"},"reference-count":56,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T00:00:00Z","timestamp":1735603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Virocarb Inc","award":["PJT-165966"],"award-info":[{"award-number":["PJT-165966"]}]},{"name":"Toronto COVID-19 Action Initiative","award":["PJT-165966"],"award-info":[{"award-number":["PJT-165966"]}]},{"name":"Connaught Innovation Fund","award":["PJT-165966"],"award-info":[{"award-number":["PJT-165966"]}]},{"name":"CIHR","award":["PJT-165966"],"award-info":[{"award-number":["PJT-165966"]}]},{"name":"PRiME fellowship (Precision Medicine Initiative at the University of Toronto)","award":["PJT-165966"],"award-info":[{"award-number":["PJT-165966"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Treatment options for viral infections are limited and viruses have proven adept at evolving resistance to many existing therapies, highlighting a significant vulnerability in our defenses. In response to this challenge, we explored the modulation of cellular RNA metabolic processes as an alternative paradigm to antiviral development. Previously, the small molecule 5342191 was identified as a potent inhibitor of HIV-1 replication by altering viral RNA accumulation at doses that minimally affect host gene expression. In this report, we document 5342191 as a potent inhibitor of adenovirus, coronavirus, and influenza replication. In each case, 5342191-mediated reduction in virus replication was associated with altered viral RNA accumulation and loss of viral structural protein expression. Interestingly, while resistant viruses were rapidly isolated for compounds targeting either virus-encoded proteases or polymerases, we have not yet isolated 5342191-resistant variants of coronavirus or influenza. As with HIV-1, 5342191\u2019s inhibition of coronaviruses and influenza is mediated through the activation of specific cell signaling networks, including GPCR and\/or MAPK signaling pathways that ultimately affect SR kinase expression. Together, these studies highlight the therapeutic potential of compounds that target cellular processes essential for the replication of multiple viruses. Not only do these compounds hold promise as broad-spectrum antivirals, but they also offer the potential of greater resilience in combating viral infections.<\/jats:p>","DOI":"10.3390\/v17010054","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T14:21:12Z","timestamp":1735654872000},"page":"54","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploiting the Achilles\u2019 Heel of Viral RNA Processing to Develop Novel Antivirals"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1979-7756","authenticated-orcid":false,"given":"Ali","family":"Zahedi Amiri","sequence":"first","affiliation":[{"name":"Virocarb Inc., Toronto, ON M8V 3Y3, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Choudhary","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Virocarb Inc., Toronto, ON M8V 3Y3, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8373-2335","authenticated-orcid":false,"given":"Subha","family":"Dahal","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filomena","family":"Grosso","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haomin","family":"Leng","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Stoilov","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Mangos","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanne","family":"Toutant","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Diseases, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lulzim","family":"Shkreta","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Diseases, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4824-2642","authenticated-orcid":false,"given":"Liliana","family":"Attisano","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0994-0042","authenticated-orcid":false,"given":"Benoit","family":"Chabot","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Diseases, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martha","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada"},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 1X8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Huesca","sequence":"additional","affiliation":[{"name":"Virocarb Inc., Toronto, ON M8V 3Y3, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8924-5682","authenticated-orcid":false,"given":"Alan","family":"Cochrane","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3647","DOI":"10.1039\/D0CS01118E","article-title":"Antiviral drug discovery: Preparing for the next pandemic","volume":"50","author":"Adamson","year":"2021","journal-title":"Chem. 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