Taylor Raymond, Kotian Pravin, Warren Travis, Panchal Rekha, Bavari Sina, Julander Justin, Dobo Sylvia, Rose Angela, El-Kattan Yahya, Taubenheim Brian, Babu Yarlagadda, Sheridan William P
BioCryst Pharmaceuticals Inc., Durham, NC, USA.
BioCryst Pharmaceuticals Inc., Durham, NC, USA.
J Infect Public Health. 2016 May-Jun;9(3):220-6. doi: 10.1016/j.jiph.2016.04.002. Epub 2016 Apr 16.
The adenosine nucleoside analog BCX4430 is a direct-acting antiviral drug under investigation for the treatment of serious and life-threatening infections from highly pathogenic viruses, such as the Ebola virus. Cellular kinases phosphorylate BCX4430 to a triphosphate that mimics ATP; viral RNA polymerases incorporate the drug's monophosphate nucleotide into the growing RNA chain, causing premature chain termination. BCX4430 is active in vitro against many RNA viral pathogens, including the filoviruses and emerging infectious agents such as MERS-CoV and SARS-CoV. In vivo, BCX4430 is active after intramuscular, intraperitoneal, and oral administration in a variety of experimental infections. In nonclinical studies involving lethal infections with Ebola virus, Marburg virus, Rift Valley fever virus, and Yellow Fever virus, BCX4430 has demonstrated pronounced efficacy. In experiments conducted in several models, both a reduction in the viral load and an improvement in survival were found to be related to the dose of BCX4430. A Phase 1 clinical trial of intramuscular administration of BCX4430 in healthy subjects is currently ongoing.
腺苷核苷类似物BCX4430是一种正在研究的直接作用抗病毒药物，用于治疗由高致病性病毒引起的严重和危及生命的感染，如埃博拉病毒。细胞激酶将BCX4430磷酸化为一种模拟ATP的三磷酸形式；病毒RNA聚合酶将该药物的单磷酸核苷酸掺入正在生长的RNA链中，导致链提前终止。BCX4430在体外对许多RNA病毒病原体具有活性，包括丝状病毒以及新兴传染病原体，如中东呼吸综合征冠状病毒（MERS-CoV）和严重急性呼吸综合征冠状病毒（SARS-CoV）。在体内，BCX4430在多种实验性感染中经肌肉注射、腹腔注射和口服给药后均具有活性。在涉及埃博拉病毒、马尔堡病毒、裂谷热病毒和黄热病毒致死性感染的非临床研究中，BCX4430已显示出显著疗效。在多个模型中进行的实验发现，病毒载量的降低和生存率的提高均与BCX4430的剂量有关。目前正在健康受试者中进行BCX4430肌肉注射的1期临床试验。
