School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551, Singapore.
Zoonotic Virus Laboratory, Institut Pasteur Korea, Seongnam, South Korea.
Antiviral Res. 2021 Jan;185:104996. doi: 10.1016/j.antiviral.2020.104996. Epub 2020 Dec 10.
Middle East Respiratory Syndrome (MERS) is a respiratory disease caused by a coronavirus (MERS-CoV). Since its emergence in 2012, nosocomial amplifications have led to its high epidemic potential and mortality rate of 34.5%. To date, there is an unmet need for vaccines and specific therapeutics for this disease. Available treatments are either supportive medications in use for other diseases or those lacking specificity requiring higher doses. The viral infection mode is initiated by the attachment of the viral spike glycoprotein to the human Dipeptidyl Peptidase IV (DPP4). Our attempts to screen antivirals against MERS led us to identify montelukast sodium hydrate (MSH), an FDA-approved anti-asthma drug, as an agent attenuating MERS-CoV infection. We showed that MSH directly binds to MERS-CoV-Receptor-Binding Domain (RBD) and inhibits its molecular interaction with DPP4 in a dose-dependent manner. Our cell-based inhibition assays using MERS pseudovirions demonstrated that viral infection was significantly inhibited by MSH and was further validated using infectious MERS-CoV culture. Thus, we propose MSH as a potential candidate for therapeutic developments against MERS-CoV infections.
中东呼吸综合征（MERS）是由一种冠状病毒（MERS-CoV）引起的呼吸道疾病。自 2012 年出现以来，医院内的扩增导致其具有高流行潜力和 34.5%的死亡率。迄今为止，针对这种疾病还没有疫苗和特效疗法。现有的治疗方法要么是用于其他疾病的支持性药物，要么是缺乏特异性需要更高剂量的药物。病毒感染模式是由病毒刺突糖蛋白与人类二肽基肽酶 4（DPP4）的结合引发的。我们试图筛选针对 MERS 的抗病毒药物，结果发现孟鲁司特钠（MSH），一种获得 FDA 批准的抗哮喘药物，可作为一种减轻 MERS-CoV 感染的药物。我们发现 MSH 可直接与 MERS-CoV-受体结合域（RBD）结合，并以剂量依赖的方式抑制其与 DPP4 的分子相互作用。我们使用 MERS 假病毒的细胞抑制测定表明，MSH 显著抑制了病毒感染，并通过使用感染性 MERS-CoV 培养物进一步验证。因此，我们提出 MSH 是治疗 MERS-CoV 感染的潜在候选药物。
