Isolation of bioactive proteins from natural product extracts

从天然产物提取物中分离生物活性蛋白

• 批准号: 10926224
• 负责人: Barry Okeefe
• 金额: $ 71.76万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10926224
• 关键词: 2019-nCoV; Amino Acid Sequence; Antibodies; Clinic; Clinical; Collaborations; Communities; Cyclic Peptides; Evaluation; Extramural Activities; Formulation; Goals; Human; Human Herpesvirus 2; Human Papillomavirus; Legal patent; Ligands; Molecular Target; Natural Products; Natural Source; Nose; Paper; Peptides; Phase I Clinical Trials; Proteins; Publications; Publishing; Reagent; Reporting; Research; Research Project Grants; Rice; Source; Viral Cancer; Work; anticancer activity; clinical development; in vivo; interest; microbicide; mutant; novel; peptide natural products; simian human immunodeficiency virus; success; three dimensional structure

Our efforts have led to the discovery of several classes of bioactive proteins as well as publications on their potential activity. This research has also led to 34 patents overall and significant interest for our discoveries from different licensees. Recent papers of particular interest include our report of fast-dissolving formulations of the protein griffithsin (GRFT) which showed in vivo activity against SHIV, HSV-2 and HPV, the expression of GRFT in rice with two other microbicide candidates which led to a new patent filing and the discovery of a new class of cyclic peptides called Tyr-lock peptides which also led to a new patent. Additional evidence for the success of PCMBS Project 2 is the fact that two Phase I clinical trials of different versions of the protein GRFT have now been successfully completed one of which whose results have been published. We continue these collaborations to help advance GRFT-based products through the clinic. Finally, two additional Phase I clinical trials of nasal formulations of the QGRFT mutant protein for use against SARS-CoV-2 have been initiated.

我们的努力导致了几类生物活性蛋白质的发现以及关于其潜在活性的出版物。这项研究还总共获得了 34 项专利，不同被许可人对我们的发现产生了浓厚的兴趣。最近特别令人感兴趣的论文包括我们关于蛋白质格里菲辛 (GRFT) 快速溶解制剂的报告，该制剂显示出针对 SHIV、HSV-2 和 HPV 的体内活性，GRFT 与其他两种候选杀菌剂一起在水稻中表达，从而产生了一种新的专利申请和一类新的环肽（称为酪氨酸锁肽）的发现也带来了一项新专利。 PCMBS 项目 2 成功的另一个证据是，不同版本的蛋白质 GRFT 的两项 I 期临床试验现已成功完成，其中一项试验的结果已发表。我们将继续开展这些合作，以帮助在临床中推进基于 GRFT 的产品。最后，针对用于对抗 SARS-CoV-2 的 QGRFT 突变蛋白鼻制剂的另外两项 I 期临床试验已经启动。

项目成果

Cyanovirin-N produced in rice endosperm offers effective pre-exposure prophylaxis against HIV-1BaL infection in vitro.

水稻胚乳中产生的 Cyanovirin-N 可在体外提供有效的暴露前预防 HIV-1BaL 感染的方法。

• 发表时间: 2016-06
• 影响因子: 6.2
• 作者: Vamvaka, E;Evans, A;Ramessar, K;Krumpe, L R H;Shattock, R J;O'Keefe, B R;Christou, P;Capell, T
• 通讯作者: Capell, T

Physicochemical characterization of the recombinant lectin scytovirin and microbicidal activity of the SD1 domain produced in rice against HIV-1.

水稻中产生的重组凝集素 scytovirin 的理化特性和 SD1 结构域针对 HIV-1 的杀菌活性。

• 发表时间: 2022-04
• 影响因子: 6.2
• 作者: Armario;Blanco;Shenoy, Shilpa R;Sun, Yi;Marfil, Silvia;Muñoz;Perez;Blanco, Julià;Izquierdo;Capell, Teresa;O'Keefe, Barry R;Christou, Paul
• 通讯作者: Christou, Paul

India-United States Dialogue on Traditional Medicine: Toward Collaborative Research and Generation of an Evidence Base.

印度-美国传统医学对话：合作研究和建立证据基础。

• 发表时间: 2018-09
• 作者: White, Jeffrey D;O'Keefe, Barry R;Sharma, Jitendra;Javed, Ghazala;Nukala, Vid;Ganguly, Aniruddha;Khan, Ikhlas A;Kumar, Nagi B;Mukhtar, Hasan;Pauli, Guido F;Walker, Larry;Sivaram, Sudha;Rajaraman, Preetha;Trimble, Edward L
• 通讯作者: Trimble, Edward L

Results of a phase 1, randomized, placebo-controlled first-in-human trial of griffithsin formulated in a carrageenan vaginal gel.

角叉菜胶阴道凝胶中配制的格里菲辛的 1 期、随机、安慰剂对照首次人体试验的结果。

• 发表时间: 2022
• 影响因子: 3.7
• 作者: Teleshova, Natalia;Keller, Marla J;Fernández Romero, José A;Friedland, Barbara A;Creasy, George W;Plagianos, Marlena G;Ray, Laurie;Barnable, Patrick;Kizima, Larisa;Rodriguez, Aixa;Cornejal, Nadjet;Melo, Claudia;Cruz Rodriguez, Gearoff;Mukhopa
• 通讯作者: Mukhopa

Cyanovirin-N binds to select SARS-CoV-2 spike oligosaccharides outside of the receptor binding domain and blocks infection by SARS-CoV-2.

Cyanovirin-N 与受体结合域外的特定 SARS-CoV-2 刺突寡糖结合，并阻断 SARS-CoV-2 的感染。

• 发表时间: 2023-03-07
• 影响因子: 11.1
• 作者: Munoz-Basagoiti, Jordana;Lima Monteiro, Fabio Luis;Krumpe, Lauren R. H.;Armario-Najera, Victoria;Shenoy, Shilpa R.;Perez-Zsolt, Daniel;Westgarth, Harrison James;Villorbina, Gemma;Bomfim, Larissa Maciel;Raich-Regue, Dalia;Nogueras, Lara;Henrich, Curtis J.;Gallemi, Marcal;Rebello Moreira, Filipe Romero;Torres, Pascual;Wilson, Jennifer;D'arc, Mirela;Marfil, Silvia;Herlinger, Alice Laschuk;Pradenas, Edwards;Higa, Luiza Mendonca;Portero-Otin, Manuel;Trinite, Benjamin;Twyman, Richard M.;Capell, Teresa;Tanuri, Amilcar;Blanco, Julia;Izquierdo-Useros, Nuria;Rech, Elibio L.;Christou, Paul;O'Keefe, Barry R.
• 通讯作者: O'Keefe, Barry R.