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The development of broad-spectrum antivirals (BSAs) focuses either on substances acting directly on viral proteins (direct-acting antivirals [DAA]) or on substances directed at the cell\u2019s own proteins (host-targeting antivirals [HTA]). Decades of development have led to the market entry of a number of DAAs with a wide range of antiviral activities; however, their clinical approval has been obtained for individual infections. HTAs have a number of advantages over DAAs, such as a wider range of antiviral activities and a high genetic barrier to viral resistance, which is undoubtedly important when preparing for a battle with an unknown pathogen. The COVID-19 pandemic has allowed for multiple clinical trials for repurposed HTAs, previously licensed for the treatment of other diseases, including cancer. Despite the enormous work done, the arsenal of BSAs capable of protecting against future pandemics caused by pathogen X is very limited. In this review, we described data on the most studied DAAs and HTAs, effective against at least two unrelated viral pathogens, focusing on those that have been studied in late preclinical and clinical trials. In the end, we highlighted alternative new approaches such as CRISPR-Cas therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00077-26","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T13:00:20Z","timestamp":1774270820000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Broad-acting antivirals: the pursuit of pan-viral therapeutics in the era of pandemics"],"prefix":"10.1128","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6160-2203","authenticated-orcid":true,"given":"Ekaterina","family":"Bayurova","sequence":"first","affiliation":[{"name":"Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis)","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1851-7441","authenticated-orcid":true,"given":"Dmitry","family":"Kostyushev","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02yqqv993","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biotechnology, Sechenov University","place":["Moscow, Russia"]},{"name":"Center for Precision Genetic Technologies for Medicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences","place":["Moscow, Russia"]},{"id":[{"id":"https:\/\/ror.org\/02yqqv993","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Genetic Technologies in Drug Development, Martsinovsky Institute of Medical Parasitology, Tropical and Vector-Borne Diseases, Sechenov University","place":["Moscow, Russia"]},{"name":"Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4293-7323","authenticated-orcid":false,"given":"Andrey","family":"Tikhonov","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02yqqv993","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Experimental Therapy of Infectious Diseases, Martsinovsky Institute of Medical Parasitology, Tropical and Vector-Borne Diseases, Sechenov University","place":["Moscow, Russia"]},{"id":[{"id":"https:\/\/ror.org\/02dn9h927","id-type":"ROR","asserted-by":"publisher"}],"name":"People\u2019s Friendship University","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Chulanov","sequence":"additional","affiliation":[{"name":"Center for Precision Genetic Technologies for Medicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences","place":["Moscow, Russia"]},{"id":[{"id":"https:\/\/ror.org\/02yqqv993","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Experimental Therapy of Infectious Diseases, Martsinovsky Institute of Medical Parasitology, Tropical and Vector-Borne Diseases, Sechenov University","place":["Moscow, Russia"]},{"id":[{"id":"https:\/\/ror.org\/02yqqv993","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Infectious Diseases, Sechenov University","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4551-7535","authenticated-orcid":false,"given":"Ilya","family":"Gordeychuk","sequence":"additional","affiliation":[{"name":"Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis)","place":["Moscow, Russia"]},{"id":[{"id":"https:\/\/ror.org\/02yqqv993","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Translational Medicine and Biotechnology, Sechenov University","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","unstructured":"WHO. 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