IND-Enabling Studies for Arenavirus Preclinical Candidate

摘要 禽流感病毒是一个不同的家族。有几种物种与严重的 人间流行性出血热(AVHF)。人类感染新城疫病毒 通常通过接触受污染的物质而发生 被感染的啮齿动物，尽管在临床环境中可能发生人与人之间的直接传播。 据估计，由感染旧大陆冠状病毒Lassa引起的AVHF 西非每年有超过30万人感染，其中15%-20%的住院患者 死亡，而幸存者往往遭受永久性后遗症。静脉给药的研究进展 非特异性抗病毒药物利巴韦林(标签外)已被用于治疗拉萨病毒感染 西非。然而，它已被证明提供有限的疗效和重大的风险 严重的副作用包括血小板减少和贫血。考虑到有限的治疗 和预防选择、死亡率/发病率、人畜共患病和 人与人之间的传播、地理移植和生物武器化 六种禽流感病毒已被确认为A类病原体。为了提供一种 治疗拉萨和其他阿拉伯病毒出血热的有效和特异的抗病毒药物 建议完成启用IND的研究和高级非临床口腔研究 临床前候选进入抑制剂具有亚纳摩尔广谱阿拉伯病毒活性和 具有明显的体内治疗效果的类药物特征。

Summary Arenaviruses comprise a diverse family. Several species are associated with severe arenaviral hemorrhagic fever (AVHF) in humans. Human infection with arenaviruses typically occurs through contact with materials contaminated with the excretions of an infected rodent although direct human- to-human transmission may occur in clinical settings. AVHF resulting from infection with the Old World arenavirus Lassa is estimated to cause over 300,000 annual infections in Western Africa, of which 15-20% of hospitalized patients die while survivors often suffer permanent sequelae. The intravenous administration of the nonspecific antiviral agent has been adopted ribavirin (off-label) for Lassa virus infections in Western Africa. However, it has been shown to provide limited efficacy and a significant risk for serious side effects including thrombocytopenia and anemia. Given the limited treatment and prophylactic options, the mortality/morbidity rate, the potential for both zoonotic and human-to-human transmission, geographical transplantation and bio-weaponization six arenaviruses have been recognized as Category A pathogens. In order to provide a potent and specific antiviral to treat Lassa and other arenavirus hemorrhagic fevers here we propose the completion of IND-enabling studies and advanced nonclinical studies for an oral preclinical candidate entry inhibitor with sub-nanomolar broad spectrum arenavirus activity and demonstrable drug-like features that exhibits remarkable in vivo therapeutic efficacy.