JP7085006B2 - エボラウイルス阻害剤の調製におけるベルバミン二塩酸塩の使用 - Google Patents
エボラウイルス阻害剤の調製におけるベルバミン二塩酸塩の使用 Download PDFInfo
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- JP7085006B2 JP7085006B2 JP2020542492A JP2020542492A JP7085006B2 JP 7085006 B2 JP7085006 B2 JP 7085006B2 JP 2020542492 A JP2020542492 A JP 2020542492A JP 2020542492 A JP2020542492 A JP 2020542492A JP 7085006 B2 JP7085006 B2 JP 7085006B2
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Description
U1.ウイルス阻害剤の調製におけるベルバミン二塩酸塩又は薬学的に許容されるその塩の使用であって、前記ウイルスは、活性化されたエンベロープ糖タンパク質を介してベルバミン二塩酸塩又はその薬学的に許容される塩に結合できるウイルスであってもよく;
U2.ウイルス阻害におけるベルバミン二塩酸塩又は薬学的に許容されるその塩の使用であって、前記ウイルスは、活性化されたエンベロープ糖タンパク質を介してベルバミン二塩酸塩又はその薬学的に許容される塩に結合できるウイルスであってもよく;
U3.ウイルス性出血熱の治療及び/又は予防のための製品(例えば薬物、ワクチン又は薬物製剤)の調製におけるベルバミン二塩酸塩又は薬学的に許容されるその塩の使用であって、前記ウイルス性出血熱は、活性化されたエンベロープ糖タンパク質を介してベルバミン二塩酸塩又はその薬学的に許容される塩に結合できるウイルスによって引き起こされる疾患であってもよく;
U4.ウイルス性出血熱の治療及び/又は予防におけるベルバミン二塩酸塩又は薬学的に許容されるその塩の使用であって、前記ウイルス性出血熱は、活性化されたエンベロープ糖タンパク質を介してベルバミン二塩酸塩又はその薬学的に許容される塩に結合できるウイルスによって引き起こされる疾患であってもよく;
U5.ウイルス活性化エンベロープ糖タンパク質と結合する製品(例えば薬物、ワクチン又は薬物製剤)の調製におけるベルバミン二塩酸塩又は薬学的に許容されるその塩の使用である。
下記実施例における真核生物発現ベクターpcDNA3.1(+)は、Invitrogen社の製品である。
EBOVが阻害剤スクリーニングモデルに入り、ベルバミン二塩酸塩がEBOV活性を特異的に阻害できることを検証した。
ベルバミン二塩酸塩の抗ウイルス活性は、その細胞毒性とは関係がない。
溶媒DMSOをブランクコントロール(DMSO)として使用した。ブランクコントロールのOD450nmを100%細胞生存率として記録した。
EBOVに対するベルバミン二塩酸塩の阻害効果は、良好な用量依存がある。
薬物の作用点実験により、ベルバミン二塩酸塩がウイルスの侵入段階に作用することが確認された。
マールブルグ組換えウイルス及びラッサ組換えウイルスモデルを使用して化合物を評価した。
バイオレイヤーの光学干渉技術を使用して、ベルバミン二塩酸塩の標的タンパク質GPclへの結合能力をインビトロで測定した。
ステップ1)ベースラインの検出:SSAセンサーを緩衝溶液に浸漬して120秒間静置して平衡状態にする;
ステップ2)センサーでビオチン化標的タンパク質GPclをインキュベートして、センサープローブをビオチン化GPclタンパク質溶液(50μg/ml)に移動して600秒間静置し、タンパク質をSSAセンサーに固定する;
ステップ3)センサーのブロック:センサーを5μMビオシチン(EZ-Biocytin、Cat.#28022、Thermo)含有溶液に移動して60sブロックする;
ステップ4)二回目のベースライン検出:センサーを緩衝溶液に移動して120s静置して平衡状態にする;
ステップ5)結合:センサーを化合物溶液に移動し、60s静置してKon値を測定する;
ステップ6)解離:センサーを緩衝溶液に移動し、60s静置してKoff値を得る;
というステップで実験を行う。実験で使用した緩衝液は、PBS(タンパク質の溶解用)及びPBS+5%DMSO(ベルバミン二塩酸塩の溶解用)である。今回の実験では、サンプルのロードと検出を別々に行い、第1のマイクロプレートには3列が含まれ、第1列ではPBSをベースラインとして使用し、第2列はビオチン化標的タンパク質GPclのロードに用い、第3列では5μMビオシチンはブロックに用いられる。センサーにロードした後に2枚目のマイクロプレートを検出する。その第1~第6列は、PBS+5%DMSOで、第7~第12列は、低濃度から高濃度の勾配(31.25μM-500μM)のベルバミン二塩酸塩である。このプロセス中に、濃度が異なる5種類のベルバミン二塩酸塩溶液を使用して、最終的なキネティック曲線を取得する。ForteBioデータ分析ソフトウェアDataAnalysis 9.0を使用して実験データを分析する。解離速度定数KD=K off/K on。
Claims (8)
- ウイルス感染を阻害するウイルス阻害剤の調製におけるベルバミン二塩酸塩の使用であって、前記ウイルスは、エボラウイルス、マールブルグウイルス及び/又はラッサウイルスである、ベルバミン二塩酸塩の使用。
- 非ヒト動物に対する、ウイルス感染の阻害のためのベルバミン二塩酸塩の使用であって、前記ウイルスは、エボラウイルス、マールブルグウイルス及び/又はラッサウイルスである、ベルバミン二塩酸塩の使用。
- ウイルス性出血熱の予防のための製品の調製におけるベルバミン二塩酸塩の使用であって、前記ウイルス性出血熱は、エボラウイルス、マールブルグウイルス及び/又はラッサウイルスによって引き起こされる疾患である、ベルバミン二塩酸塩の使用。
- 非ヒト動物に対する、ウイルス性出血熱の予防におけるベルバミン二塩酸塩の使用であって、前記ウイルス性出血熱は、エボラウイルス、マールブルグウイルス及び/又はラッサウイルスによって引き起こされる疾患である、ベルバミン二塩酸塩の使用。
- エボラウイルス活性化エンベロープ糖タンパク質と結合することによりエボラウイルスの感染を阻害するための製品の調製におけるベルバミン二塩酸塩の使用。
- エボラウイルス、マールブルグウイルス及び/又はラッサウイルスによる動物のウイルス感染を阻害するウイルス阻害剤であって、ベルバミン二塩酸塩を含む、ウイルス阻害剤。
- 非ヒト動物にベルバミン二塩酸塩を投与することによって非ヒト動物のウイルス感染を阻害することを含み、
前記ウイルスは、エボラウイルス、マールブルグウイルス及び/又はラッサウイルスである、非ヒト動物のウイルス感染を阻害する方法。 - 非ヒト動物にベルバミン二塩酸塩を投与してウイルス性出血熱の予防を行うことを含み、
前記ウイルス性出血熱は、エボラウイルス、マールブルグウイルス及び/又はラッサウイルスによって引き起こされる疾患である、ウイルス性出血熱の予防方法。
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CN109125323B (zh) | 2020-07-03 |
US11654141B2 (en) | 2023-05-23 |
JP2020537693A (ja) | 2020-12-24 |
WO2020024719A1 (zh) | 2020-02-06 |
EP3669875A1 (en) | 2020-06-24 |
EP3669875A4 (en) | 2020-07-29 |
CN109125323A (zh) | 2019-01-04 |
US20230321079A1 (en) | 2023-10-12 |
CA3083540A1 (en) | 2020-02-06 |
CA3083540C (en) | 2022-07-19 |
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