Improved Treatment for Zoonotic BV Infections

人畜共患 BV 感染的改进治疗

• 批准号: 9302579
• 负责人: R EBERLE
• 金额: $ 24.22万
• 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/9302579
• 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; Drug Utilization; Effectiveness; Foundations; Ganciclovir; Genotype; Grant; Herpesviridae; Human; Human Resources; Infection; Invaded; Macaca; Macaca fascicularis; Macaca mulatta; Modification; Monkeys; Morbidity - disease rate; Mus; Neuraxis; Neurologic; Neurologic Symptoms; Outcome; Papio; Patients; Peripheral; Persons; Pharmaceutical Preparations; Pharmacotherapy; Privatization; Prophylactic treatment; Public Health; Recommendation; Regimen; Research; Ribonucleotide Reductase; Ribonucleotide Reductase Inhibitor; Sensory Nerve Endings; Simplexvirus; Site; Skin; Survivors; Testing; Therapeutic Intervention; Time; Topical application; Treatment Efficacy; Treatment Protocols; Viral; Virus; Virus Diseases; Virus Replication; Work; Zoonoses; biomedical resource; clinical application; effective therapy; efficacy testing; experience; experimental study; financial incentive; follow-up; helicase; improved; in vivo; mortality; mouse model; novel therapeutics; prevent; 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 猴子B病毒（BV）是猕猴（恒河猴，cynomolgus）常见的疱疹病毒 猴子是生物医学研究的宝贵资源。当BV传输到 人类，约80％的患者死亡，幸存者经常经常经历进行性神经系统 衰落，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 用于治疗单纯疱疹病毒（HSV）感染，并且针对BV的有效性较小 比HSV。即使用Ganciclovir（GCV）治疗，最有效的药物也是一些BV患者 仍然死了。在小鼠中的研究还表明，当前建议的治疗方案可能是 有缺陷，允许未发现的BV感染入侵中枢神经系统，导致 患者生存的机会大大减少。由于专门针对BV的新药是 由于缺乏经济激励，使用现有抗病毒药的财务激励疗法，不太可能开发 需要优化。在拟议的研究药物中，证明对HSV有效和 某些实验药物将通过全身性测试BV的体内功效 使用鼠标模型给药。初步实验表明使用药物 局部可以提供与系统管理一样有效的BV的保护 毒品。此外，Cidofovir（CDV）似乎比GCV更有效（最多 目前建议用于治疗BV感染的有效药物）和实验药物 与GCV或CDV具有不同的作用方式也有效，可以提高BV 在双重药物方案中使用以增加治疗功效的可能性。这些结果需要 随后进行其他研究，以验证使用局部药物输送作为一种手段 防止神经BV感染，使用CDV治疗BV感染以及潜力 双重药物方案的功效。该项目将产生所需的确认数据并测试 双重药物方案的功效。结果将成为理性科学基础 可能修改现有建议治疗人畜共患性BV感染的建议。