{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T22:36:41Z","timestamp":1785191801827,"version":"3.55.0"},"reference-count":78,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2000,5,1]],"date-time":"2000-05-01T00:00:00Z","timestamp":957139200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2000,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            MRL-1237, [1-(4-fluorophenyl)-2-(4-imino-1,4-dihydropyridin-1-yl) methylbenzimidazole hydrochloride], is a potent and selective inhibitor of the replication of enteroviruses. To reveal the target molecule of MRL-1237 in viral replication, we selected spontaneous MRL-1237-resistant poliovirus mutants. Of 15 MRL-1237-resistant mutants obtained, 14 were cross-resistant to guanidine hydrochloride (\n            <jats:italic>mrgr<\/jats:italic>\n            ), while 1 was susceptible (\n            <jats:italic>mrgs<\/jats:italic>\n            ). Sequence analysis of the 2C region revealed that the 14\n            <jats:italic>mrgr<\/jats:italic>\n            mutants contained a single nucleotide substitution that altered an amino acid residue from Phe-164 to Tyr. The\n            <jats:italic>mrgs<\/jats:italic>\n            mutant, on the other hand, contained a substitution of Ile-120 to Val. Through the construction of a cDNA-derived mutant, we confirmed that the single mutation at Phe-164 was really responsible for the reduced susceptibility to MRL-1237. MRL-1237 inhibited poliovirus-specific RNA synthesis in HeLa cells infected with a wild strain but not with an F164Y mutant. We furthermore examined the effect of mutations of the 2C region on the drug sensitivity of cDNA-derived guanidine-resistant and -dependent mutants. Two guanidine-resistant mutants were cross-resistant to MRL-1237 but remained susceptible to another benzimidazole, enviroxime. Either MRL-1237 or guanidine stimulated the viral replication of two guanidine-dependent mutants, but enviroxime did not. These results indicate that MRL-1237, like guanidine, targets the 2C protein of poliovirus for its antiviral effect.\n          <\/jats:p>","DOI":"10.1128\/jvi.74.9.4146-4154.2000","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:06:37Z","timestamp":1027764397000},"page":"4146-4154","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":51,"title":["Mutations in the 2C Region of Poliovirus Responsible for Altered Sensitivity to Benzimidazole Derivatives"],"prefix":"10.1128","volume":"74","author":[{"given":"Hiroyuki","family":"Shimizu","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Department of Virology II, National Institute of Infectious Diseases, Musashimurayama-shi, Tokyo 208-0011,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanobu","family":"Agoh","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Central 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and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuo","family":"Yoneyama","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Virology II, National Institute of Infectious Diseases, Musashimurayama-shi, Tokyo 208-0011,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akio","family":"Hagiwara","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Virology II, National Institute of Infectious Diseases, Musashimurayama-shi, Tokyo 208-0011,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuo","family":"Miyamura","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Virology II, National Institute of Infectious Diseases, Musashimurayama-shi, Tokyo 208-0011,1 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