Improved Treatment for Zoonotic BV Infections

人畜共患 BV 感染的改进治疗

• 批准号: 9151134
• 负责人: R EBERLE
• 金额: $ 25.5万
• 依托单位: OKLAHOMA STATE UNIVERSITY STILLWATER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9151134
• 关键词: Antiviral Agents; Asia; Biomedical Research; Central Nervous System Infections; Cercopithecine Herpesvirus 1; Cidofovir; Clinical; DNA Primase; Data; Dose; Drops; Drug Delivery Systems; Effectiveness; Foundations; Ganciclovir; Genotype; Grant; Herpesviridae; Human; Human Resources; Infection; Invaded; Licensing; Macaca; Macaca fascicularis; Macaca mulatta; Modification; Monkeys; Morbidity - disease rate; Mus; Neuraxis; Neurologic; Outcome; Papio; Patients; Peripheral; Persons; Pharmaceutical Preparations; Pharmacotherapy; Prophylactic treatment; Public Health; Recommendation; Regimen; Research; Resources; Ribonucleotide Reductase; Ribonucleotide Reductase Inhibitor; Sensory Nerve Endings; Simplexvirus; Site; Skin; Survivors; Symptoms; Testing; Therapeutic Intervention; Time; Topical application; Treatment Efficacy; Treatment Protocols; Viral; Virus; Virus Diseases; Virus Replication; Work; base; clinical application; effective therapy; efficacy testing; experience; financial incentive; follow-up; helicase; improved; in vivo; mortality; mouse model; novel therapeutics; prevent; research study; therapy development; wound

ABSTRACT Monkey B virus (BV) is a herpesvirus common in macaque (rhesus, cynomolgus) monkeys which are an invaluable resource for biomedical research. When BV is transmitted to humans, ~80% of patients die and survivors frequently experience progressive neurological decline, making BV the single greatest zoonotic danger facing research and veterinary personnel who work with macaques. Drugs currently used to treat BV infections were developed for treatment of herpes simplex virus (HSV) infections, and are all are less effective against BV than HSV. Even when treated with ganciclovir (GCV), the most effective drug, some BV patients still die. Studies in mice also suggest that the current recommended treatment protocol may be flawed, allowing undetected BV infections to invade the central nervous system, resulting in a drastically diminished chance of patient survival. Since new drugs specifically targeted at BV are unlikely to be developed due to a lack of financial incentive, therapy using existing antivirals needs to be optimized. In the proposed study drugs shown to be effective against HSV and some experimental drugs will be tested for in vivo efficacy against BV by systemic administration using a mouse model. Preliminary experiments indicate that drugs applied topically can provide protection against BV that is as effective as systemically administered drugs. In addition, cidofovir (CDV) appears to be more effective against BV than GCV (the most effective drug currently recommended for treatment of BV infections) and an experimental drug having a different mode of action than GCV or CDV is also effective against BV, raising the possibility of its use in a dual drug regimen for added treatment efficacy. These results need to be followed up with additional research to validate use of topical drug delivery as a means of preventing neurological BV infections, use of CDV to treat BV infections, and the potential efficacy of dual drug regimens. This project will produce the needed confirmatory data and test the efficacy of dual drug regimens. The results will serve as a rational scientific basis for possible modification of existing recommendations for treatment of zoonotic BV infections.

抽象的 猴 B 病毒 (BV) 是一种常见于猕猴（恒河猴、食蟹猴）的疱疹病毒 猴子是生物医学研究的宝贵资源。当 BV 传输至 人类，约 80% 的患者死亡，幸存者经常经历进行性神经系统疾病 下降，使 BV 成为研究和兽医面临的最大人畜共患危险 与猕猴一起工作的人员。目前用于治疗 BV 感染的药物已开发出来 用于治疗单纯疱疹病毒 (HSV) 感染，但对 BV 的效果均较差 比单纯疱疹病毒。即使使用最有效的药物更昔洛韦 (GCV) 治疗，一些 BV 患者 还是死了。对小鼠的研究还表明，目前推荐的治疗方案可能是 有缺陷，导致未检测到的 BV 感染侵入中枢神经系统，导致 大大降低了患者的生存机会。由于专门针对 BV 的新药 由于缺乏经济激励，不太可能开发使用现有抗病毒药物的疗法 需要优化。在拟议的研究中，药物被证明对 HSV 有效，并且 一些实验药物将通过全身系统测试其对抗 BV 的体内功效 使用小鼠模型进行管理。初步实验表明，所用药物 局部给药可提供与全身给药一样有效的 BV 保护 药物。此外，西多福韦 (CDV) 似乎比 GCV（最有效）对抗 BV 更有效。 目前推荐用于治疗 BV 感染的有效药物）和实验药物 与 GCV 或 CDV 不同的作用方式也能有效对抗 BV，从而提高 其在双药治疗方案中使用以增加治疗效果的可能性。这些结果需要 进行额外的研究以验证局部给药作为一种手段的使用 预防神经系统 BV 感染、使用 CDV 治疗 BV 感染以及潜在的 双药方案的疗效。该项目将产生所需的验证数据并进行测试 双药方案的疗效。研究结果将作为合理的科学依据 可能修改治疗人畜共患 BV 感染的现有建议。