Targeting Covid-19 with a Therapeutic Interfering Particle

使用治疗性干扰粒子针对 Covid-19

• 批准号: 10383399
• 负责人: Raul Andino
• 金额: $ 29.59万
• 依托单位: ALEPH THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-05 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10383399
• 关键词: 2019-nCoV; A549; ACE2; Alpha Particles; Animal Experiments; Animal Model; Antiviral Agents; Body Weight; Brunhilde Virus; COVID-19; COVID-19 pandemic; Cell Culture Techniques; Cells; Clinical; Clinical Markers; Coxsackie Viruses; Data; Development; Disease; Drug or chemical Tissue Distribution; Enterovirus; Epithelial Cells; Funding; Future; Goals; Immune response; Infection; Influenza A virus; Innate Immune Response; K-18 conjugate; Lung; Measures; Messenger RNA; Monitor; Mus; Organoids; Process; Production; Public Health; RNA; Respiratory Disease; Rhinovirus; Safety; Therapeutic; Toxic effect; Transgenic Mice; Viral; Virus; Work; airway epithelium; base; efficacy evaluation; efficacy testing; experimental study; lipid nanoparticle; mouse model; novel strategies; novel therapeutics; particle; prevent; programs; prophylactic; respiratory; respiratory virus; treatment response

SUMMARY The Covid-19 pandemic caused by Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) is currently the most important public health crisis in the world. Given the unprecedented scope of this disease, it is critical to explore novel strategies to mitigate this crisis. Aleph Therapeutics and UCSF have jointly developed eTIP1, a Therapeutic Interfering Particle. eTIP1 was developed under a DARPA-funded program and shows potent broad-spectrum activity across enteroviruses (Poliovirus Type 1 and 3, EVA71, and Coxsackievirus B3) as well as respiratory viruses EV-D68/HRV-87, Rhinovirus A16 and A1B, and Influenza A. Recently we have shown that eTIP1 significantly inhibits replication of SARS-CoV-2 both in cell culture and in K18-ACE2 mice. Given these results, it is critical to thoroughly evaluate eTIP1 as a potential agent against SARS-CoV-2. This work could be the starting point for a potential therapy or prophylactic agent against SARS-CoV-2. This would also represent a significant breakthrough for the development of a broad-spectrum antiviral agent that could potentially target current and future viral threats.

总结 由严重急性呼吸道冠状病毒2型（SARS-CoV-2）引起的2019冠状病毒病大流行目前正在 世界上最严重的公共卫生危机。鉴于这一疾病前所未有的范围， 探索新的策略来缓解这场危机。Aleph Therapeutics和UCSF联合开发了eTIP 1， 治疗性干扰颗粒。eTIP 1是在DARPA资助的项目下开发的， 对肠道病毒（脊髓灰质炎病毒1型和3型、EVA 71和柯萨奇病毒B3）也具有广谱活性 如呼吸道病毒EV-D 68/HRV-87、鼻病毒A16和A1 B以及甲型流感病毒。最近我们发现 eTIP 1在细胞培养和K18-ACE 2小鼠中均显著抑制SARS-CoV-2的复制。给定 这些结果表明，彻底评估eTIP 1作为抗SARS-CoV-2的潜在药物至关重要。这项工作 可能是针对SARS-CoV-2的潜在治疗或预防剂的起点。这也将 代表了开发广谱抗病毒剂的重大突破， 潜在地针对当前和未来的病毒威胁。