University of the Ryukyus · Faculty of Science · 助教

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• Onnamides A and B Suppress Hepatitis B Virus Transcription by Inhibiting Viral Promoter Activity2026 · We recently reported that onnamide A, a marine-derived natural compound isolated from the sponge Theonella sp., inhibits the entry process of SARS-CoV-2 infection. However, its antiviral activity against other viruses remains largely unexplored. Here, we investigated the effects of onnamide A and its structurally related analog, onnamide B, on hepatitis B virus (HBV) infection. Using iNTCP cells, a hepatoblastoma-derived cell line permissive to HBV infection, we found that onnamides A and B exhibited cytotoxicity, with CC50 values of 0.53 ± 0.10 μM and 2.37 ± 0.25 μM, respectively. Following HBV infection, the levels of total HBV RNA were significantly reduced by onnamide A (IC50 = 0.06 ± 0.01 μM) and onnamide B (IC50 = 0.23 ± 0.06 μM). Notably, both compounds markedly decreased the levels of HBV pregenomic RNA. Furthermore, significant inhibition was particularly evident when onnamide treatment was initiated after HBV infection. Consistent with these observations, onnamides did not affect HBV binding, entry, or covalently closed circular DNA formation, but they significantly suppressed HBV RNA transcription. In particular, the transcriptional activities driven by the core and X promoters were markedly inhibited by onnamide treatment. Taken together, our findings demonstrate that onnamides possess potent anti-HBV activity and highlight their potential as candidate compounds targeting HBV RNA transcription.
• A Novel Sesterterpenoid, Petrosaspongin and γ-Lactone Sesterterpenoids with Leishmanicidal Activity from Okinawan Marine Invertebrates2025 · Leishmaniasis is a major public health problem, especially affecting vulnerable populations in tropical and subtropical regions. The disease is endemic in 90 countries, and with millions of people at risk, it is seen as one of the ten most neglected tropical diseases. Current treatments face challenges such as high toxicity, side effects, cost, and growing drug resistance. There is an urgent need for safer, affordable treatments, especially for cutaneous leishmaniasis (CL), the most common form. Marine invertebrates have long been resources for discovering bioactive compounds such as sesterterpenoids. Using bioassay-guided fractionations against cutaneous-type leishmaniasis promastigotes, we identified a novel furanosesterterpenoid, petrosaspongin from Okinawan marine sponges and a nudibranch, along with eight known sesterterpenoids, hippospongins and manoalides. The elucidated structure of petrosaspongin features a β-substituted furane ring, a tetronic acid, and a conjugated triene. The sesterterpenoids with a γ-butenolide group exhibited leishmanicidal activity against Leishmania major promastigotes, with IC50 values ranging from 0.69 to 53 μM. The structure–activity relationship and molecular docking simulation suggest that γ-lactone is a key functional group for leishmanicidal activity. These findings contribute to the ongoing search for more effective treatments against CL.
• Demethylmycemycin A, a dibenzoxazepinone from the marine-derived Dactylosporangium sp. OK1079, with prostate cancer suppressive effects via targeting BRK-FAK-STAT3 axis2025 · Elsbaey, M; Tarun, MTI; Alnajjar, R; Jomori, T; Tanaka, J; Oku, N; El Sayed, K; Igarashi, Y
• Onnamides and a Novel Analogue, Onnamide G, as Potent Leishmanicidal Agents.2025 · Jomori T, Higa N, Tyas TA, Matsuura N, Ueda Y, Suetake A, Miyazaki S, Watanabe S, Arizono S, Hayashi Y, Yasumoto K, Ise Y, Wakimoto T, Yasumoto-Hirose M, Tanaka J, Mori-Yasumoto K

• 水平伝播を起点とする海綿由来有用天然物の生合成研究基盤の構築2024 · 海綿動物由来の生理活性物質は、生体内でのシグナル伝達機構や作用点の解明のみならず、創薬への応用の観点からも重要な研究対象である。近年、海綿由来天然物の設計図である生合成遺伝子の研究が行われ、その真の生産者は海綿宿主ではなく、共生微生物であることが明らかになってきた。さらに天然物の生合成遺伝子の詳細な解析によると、生合成遺伝子クラスターは水平伝播により微生物間で授受されていることが示唆されている。本研究課題では、海綿動物における微生物間の遺伝子水平伝播に着目し、遺伝子情報を濃縮することで、効率的に海洋天然物の生合成遺伝子クラスターの探索およびそれら有用遺伝子の機能解析を実施する。
• 海綿における水平伝播を起点とした生理活性天然物生合成遺伝子の探索と解析海洋生物である海綿からは稀少かつユニークな構造を有する生理活性物質が単離されている。近年、海綿メタゲノミクスによりその真の生産者は、海綿に共生する微生物であることが明らかになってきた。さらに、生理活性物質の生合成遺伝子の詳細な解析によると、生合成遺伝子クラスターは水平伝播により微生物間で授受されていることが示唆されている。本研究課題では、海綿における微生物間の遺伝子水平伝播を活用した天然物の生合成遺伝子クラスターの探索および機能解析を目指す。医薬品として有望な化合物の生合成研究は、量的供給法の確立や新たな生体触媒のレパートリー拡充へと繋がる。

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