Long Jason, Wright Edward, Molesti Eleonora, Temperton Nigel, Barclay Wendy
Section of Virology, St Mary's Campus, Imperial College London, London, W2 1PG, UK.
Viral Pseudotype Unit (Fitzrovia), Faculty of Science and Technology, University of Westminster, London, W1W 6UW, UK.
F1000Res. 2015 Jan 29;4:30. doi: 10.12688/f1000research.6085.2. eCollection 2015.
Emerging viral diseases pose a threat to the global population as intervention strategies are mainly limited to basic containment due to the lack of efficacious and approved vaccines and antiviral drugs. The former was the only available intervention when the current unprecedented Ebolavirus (EBOV) outbreak in West Africa began. Prior to this, the development of EBOV vaccines and anti-viral therapies required time and resources that were not available. Therefore, focus has turned to re-purposing of existing, licenced medicines that may limit the morbidity and mortality rates of EBOV and could be used immediately. Here we test three such medicines and measure their ability to inhibit pseudotype viruses (PVs) of two EBOV species, Marburg virus (MARV) and avian influenza H5 (FLU-H5). We confirm the ability of chloroquine (CQ) to inhibit viral entry in a pH specific manner. The commonly used proton pump inhibitors, Omeprazole and Esomeprazole were also able to inhibit entry of all PVs tested but at higher drug concentrations than may be achieved in vivo. We propose CQ as a priority candidate to consider for treatment of EBOV.
新兴病毒性疾病对全球人口构成威胁，由于缺乏有效的、已获批的疫苗和抗病毒药物，干预策略主要限于基本的控制措施。在西非当前前所未有的埃博拉病毒（EBOV）疫情爆发之初，前者是唯一可用的干预措施。在此之前，埃博拉病毒疫苗和抗病毒疗法的研发需要时间和资源，而当时并不具备这些条件。因此，人们的注意力已转向重新利用现有的已获许可药物，这些药物可能会降低埃博拉病毒的发病率和死亡率，并且可以立即使用。在此，我们测试了三种此类药物，并测定了它们抑制两种埃博拉病毒——马尔堡病毒（MARV）和禽流感H5（FLU-H5）假型病毒（PVs）的能力。我们证实了氯喹（CQ）以pH特异性方式抑制病毒进入的能力。常用的质子泵抑制剂奥美拉唑和埃索美拉唑也能够抑制所有测试假型病毒的进入，但所需药物浓度高于体内可能达到的浓度。我们提议将氯喹作为治疗埃博拉病毒的优先考虑候选药物。
