Repurposing of Clinically Developed Drugs for Treatment of Middle East Respiratory Syndrome Coronavirus Infection
Repurposing of Clinically Developed Drugs for Treatment of Middle East Respiratory Syndrome Coronavirus Infection
复制标题
DOI：
10.1128/aac.03036-14
复制
发表时间：
2014-08-01
影响因子：
4.9
通讯作者：
Frieman, Matthew B.
中科院分区：
文献类型：
--
作者：
Dyall, Julie;Coleman, Christopher M.;Frieman, Matthew B.
新发感染的爆发给卫生专业人员带来了独特的挑战，即在临床上选择适当的药物治疗方法，几乎没有时间进行药物测试和开发。通常情况下，临床医生只剩下一般的支持性治疗和通常未经测试的恢复期血浆作为可用的治疗选择。将已批准的药物重新用于新的适应症对临床医生、研究人员、公共卫生机构、药物开发人员和资助机构来说是一种有吸引力的替代方案。考虑到新产品的开发时间和制造要求，重新利用现有药物可能是应对新出现病毒引起的疫情的唯一解决方案。在本文描述的研究中，筛选了290种化合物的库，以确定其对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）的抗病毒活性。用于包含在库中的化合物的选择取决于当前或先前的FDA批准或先进的临床开发。包括一些具有明确的细胞途径作为靶点的药物。总共鉴定了27种对MERS-CoV和SARS-CoV都具有活性的化合物。这些化合物属于13种不同类别的药物，包括用于癌症治疗的雌激素受体抑制剂和用作抗精神病药的多巴胺受体抑制剂。在这些筛选中鉴定的药物为体内研究以及纳入正在进行的临床研究提供了新的靶点。
Outbreaks of emerging infections present health professionals with the unique challenge of trying to select appropriate pharmacologic treatments in the clinic with little time available for drug testing and development. Typically, clinicians are left with general supportive care and often untested convalescent-phase plasma as available treatment options. Repurposing of approved pharmaceutical drugs for new indications presents an attractive alternative to clinicians, researchers, public health agencies, drug developers, and funding agencies. Given the development times and manufacturing requirements for new products, repurposing of existing drugs is likely the only solution for outbreaks due to emerging viruses. In the studies described here, a library of 290 compounds was screened for antiviral activity against Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). Selection of compounds for inclusion in the library was dependent on current or previous FDA approval or advanced clinical development. Some drugs that had a well-defined cellular pathway as target were included. In total, 27 compounds with activity against both MERS-CoV and SARS-CoV were identified. The compounds belong to 13 different classes of pharmaceuticals, including inhibitors of estrogen receptors used for cancer treatment and inhibitors of dopamine receptor used as antipsychotics. The drugs identified in these screens provide new targets for in vivo studies as well as incorporation into ongoing clinical studies.