Rabaan Ali A, Alahmed Shamsah H, Bazzi Ali M, Alhani Hatem M
Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran 31311, Saudi Arabia.
Specialty Paediatric Medicine, Qatif Central Hospital, Qatif 32654, Saudi Arabia.
J Med Microbiol. 2017 Sep;66(9):1261-1274. doi: 10.1099/jmm.0.000565. Epub 2017 Aug 31.
There have been 2040 laboratory-confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) in 27 countries, with a mortality rate of 34.9 %. There is no specific therapy. The current therapies have mainly been adapted from severe acute respiratory syndrome (SARS-CoV) treatments, including broad-spectrum antibiotics, corticosteroids, interferons, ribavirin, lopinavir-ritonavir or mycophenolate mofetil, and have not been subject to well-organized clinical trials. The development of specific therapies and vaccines is therefore urgently required. We examine existing and potential therapies and vaccines from a molecular perspective. These include viral S protein targeting; inhibitors of host proteases, including TMPRSS2, cathepsin L and furin protease, and of viral M(pro) and the PL(pro) proteases; convalescent plasma; and vaccine candidates. The Medline database was searched using combinations and variations of terms, including 'Middle East respiratory syndrome coronavirus', 'MERS-CoV', 'SARS', 'therapy', 'molecular', 'vaccine', 'prophylactic', 'S protein', 'DPP4', 'heptad repeat', 'protease', 'inhibitor', 'anti-viral', 'broad-spectrum', 'interferon', 'convalescent plasma', 'lopinavir ritonavir', 'antibodies', 'antiviral peptides' and 'live attenuated viruses'. There are many options for the development of MERS-CoV-specific therapies. Currently, MERS-CoV is not considered to have pandemic potential. However, the high mortality rate and potential for mutations that could increase transmissibility give urgency to the search for direct, effective therapies. Well-designed and controlled clinical trials are needed, both for existing therapies and for prospective direct therapies.
27个国家已出现2040例中东呼吸综合征冠状病毒(MERS-CoV)实验室确诊病例,死亡率为34.9%。目前尚无特效疗法。当前的治疗方法主要是借鉴严重急性呼吸综合征(SARS-CoV)的治疗方案,包括广谱抗生素、皮质类固醇、干扰素、利巴韦林、洛匹那韦-利托那韦或霉酚酸酯,但这些疗法尚未经过系统的临床试验。因此,迫切需要研发特效疗法和疫苗。我们从分子角度审视现有的和潜在的疗法及疫苗。这些包括针对病毒S蛋白;宿主蛋白酶抑制剂,包括跨膜丝氨酸蛋白酶2(TMPRSS2)、组织蛋白酶L和弗林蛋白酶,以及病毒M蛋白酶(M(pro))和木瓜蛋白酶样蛋白酶(PL(pro));康复期血浆;以及候选疫苗。使用包括“中东呼吸综合征冠状病毒”、“MERS-CoV”、“SARS”、“疗法”、“分子”、“疫苗”、“预防”、“S蛋白”、“二肽基肽酶4(DPP4)”、“七肽重复序列”、“蛋白酶”、“抑制剂”、“抗病毒”、“广谱”、“干扰素”、“康复期血浆”、“洛匹那韦利托那韦”、“抗体”、“抗病毒肽”和“减毒活病毒”等术语的组合及变体对医学文献数据库(Medline)进行了检索。研发针对MERS-CoV的特效疗法有多种选择。目前,MERS-CoV不被认为具有大流行潜力。然而,高死亡率以及可能增加传播性的突变潜力使得寻找直接有效的疗法变得紧迫。对于现有疗法和前瞻性直接疗法,都需要精心设计和严格控制的临床试验。