Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederik, MD, USA.
Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD, USA.
J Gen Virol. 2014 Mar;95(Pt 3):571-577. doi: 10.1099/vir.0.061911-0. Epub 2013 Dec 9.
The Middle East respiratory syndrome coronavirus (MERS-CoV) presents a novel emerging threat to public health worldwide. Several treatments for infected individuals have been suggested including IFN, ribavirin and passive immunotherapy with convalescent plasma. Administration of IFN-α2b and ribavirin has improved outcomes of MERS-CoV infection in rhesus macaques when administered within 8 h post-challenge. However, detailed and systematic evidence on the activity of other clinically available drugs is limited. Here we compared the susceptibility of MERS-CoV with different IFN products (IFN-α2b, IFN-γ, IFN-universal, IFN-α2a and IFN-β), as well as with two antivirals, ribavirin and mycophenolic acid (MPA), against MERS-CoV (Hu/Jordan-N3/2012) in vitro. Of all the IFNs tested, IFN-β showed the strongst inhibition of MERS-CoV in vitro, with an IC₅₀ of 1.37 U ml(-1), 41 times lower than the previously reported IC₅₀ (56.08 U ml(-1)) of IFN-α2b. IFN-β inhibition was confirmed in the virus yield reduction assay, with an IC90 of 38.8 U ml(-1). Ribavirin did not inhibit viral replication in vitro at a dose that would be applicable to current treatment protocols in humans. In contrast, MPA showed strong inhibition, with an IC₅₀ of 2.87 µM. This drug has not been previously tested against MERS-CoV and may provide an alternative to ribavirin for treatment of MERS-CoV. In conclusion, IFN-β, MPA or a combination of the two may be beneficial in the treatment of MERS-CoV or as a post-exposure intervention in high-risk patients with known exposures to MERS-CoV.
中东呼吸综合征冠状病毒（MERS-CoV）对全球公共卫生构成了新的新兴威胁。已经提出了几种针对感染个体的治疗方法，包括 IFN、利巴韦林和恢复期血浆的被动免疫疗法。在猕猴感染 MERS-CoV 后 8 小时内给予 IFN-α2b 和利巴韦林，可以改善 MERS-CoV 感染的结局。然而，关于其他临床可用药物活性的详细和系统证据有限。在这里，我们比较了不同 IFN 产品（IFN-α2b、IFN-γ、IFN-通用、IFN-α2a 和 IFN-β）以及两种抗病毒药物利巴韦林和吗替麦考酚酯（MPA）对 MERS-CoV（Hu/Jordan-N3/2012）的体外敏感性。在所有测试的 IFN 中，IFN-β 对 MERS-CoV 的抑制作用最强，IC₅₀为 1.37 U ml(-1)，比之前报道的 IFN-α2b 的 IC₅₀（56.08 U ml(-1))低 41 倍。IFN-β 抑制作用在病毒产量减少测定中得到证实，IC₉₀为 38.8 U ml(-1)。利巴韦林在不会抑制病毒复制的剂量下不适用当前的人类治疗方案。相比之下，MPA 表现出强烈的抑制作用，IC₅₀为 2.87 µM。这种药物以前没有针对 MERS-CoV 进行过测试，可能是利巴韦林治疗 MERS-CoV 的替代药物。总之，IFN-β、MPA 或两者的组合可能对治疗 MERS-CoV 或对已知接触 MERS-CoV 的高危患者进行接触后干预有益。
