RRC ID 68386
著者 Uemura K, Nobori H, Sato A, Sanaki T, Toba S, Sasaki M, Murai A, Saito-Tarashima N, Minakawa N, Orba Y, Kariwa H, Hall WW, Sawa H, Matsuda A, Maenaka K.
タイトル 5-Hydroxymethyltubercidin exhibits potent antiviral activity against flaviviruses and coronaviruses, including SARS-CoV-2.
ジャーナル iScience
Abstract Newly emerging or re-emerging viral infections continue to cause significant morbidity and mortality every year worldwide, resulting in serious effects on both health and the global economy. Despite significant drug discovery research against dengue viruses (DENVs) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), no fully effective and specific drugs directed against these viruses have been discovered. Here, we examined the anti-DENV activity of tubercidin derivatives from a compound library from Hokkaido University and demonstrated that 5-hydroxymethyltubercidin (HMTU, HUP1108) possessed both potent anti-flavivirus and anti-coronavirus activities at submicromolar levels without significant cytotoxicity. Furthermore, HMTU inhibited viral RNA replication and specifically inhibited replication at the late stages of the SARS-CoV-2 infection process. Finally, we demonstrated that HMTU 5'-triphosphate inhibited RNA extension catalyzed by the viral RNA-dependent RNA polymerase. Our findings suggest that HMTU has the potential of serving as a lead compound for the development of a broad spectrum of antiviral agents, including SARS-CoV-2.
巻・号 24(10)
ページ 103120
公開日 2021-10-22
DOI 10.1016/j.isci.2021.103120
PII S2589-0042(21)01088-9
PMID 34541466
PMC PMC8433052
IF 4.447
リソース情報
遺伝子材料 CSII-CMV-MCS-IRES2-Bsd (RDB04385)
ヒト・動物細胞 HuH-7(RCB1942) A549(RCB0098) CACO-2(RCB0988) 293T(RCB2202)