綜述：針對流感、RSV和MERS-CoV感染的治療方法和新型候選療法

近日，美國西奈山醫學院Mohammad Amin Behzadi與Victor H. Leyva-Grado在國際學術期刊Front. Microbiol發表了題為Overview of Current Therapeutics and Novel Candidates Against Influenza, Respiratory Syncytial Virus, and Middle East Respiratory Syndrome Coronavirus Infections

的文章，綜述了目前可用於治療流感和呼吸道合胞病毒（RSV）的抗病毒藥物以及這些呼吸道病毒感染的潛在新療法，同時也涉及目前使用廣譜抗病毒藥治療MERS-CoV感染患者的療法。

呼吸道病毒感染的突發和再發對全球公共衛生構成重大威脅。中國H7N9禽流感數量增加，包括高致病性H7N9病毒株的出現、高致病性禽流感（HPAI）H5N1病毒的持續爆發，季節性流感病毒（H3N2var）的新變種，以及中東呼吸綜合症冠狀病毒（MERS-CoV）的出現，這些都凸顯了要開發新型、更有效的抗病毒療法的重要和重要需求。

本綜述重點介紹目前正在開發的治療流感，RSV和MERS-CoV感染的療法,簡要回顧美國聯邦藥品管理局（FDA）批准的藥物以及臨床試驗中的藥物（圖1），綜述了目前可用於治療流感和呼吸道合胞病毒的抗病毒藥物以及這些呼吸道病毒感染的潛在新療法，同時也涉及目前使用廣譜抗病毒藥治療MERS-CoV感染患者的療法(表1)。

圖1. 不同抗病毒藥物作用機制。(A)流感病毒、(B)呼吸道合胞體病毒和(C)中東呼吸綜合征冠狀病毒的病毒生命周期圖，顯示每種治療方法在何處發揮其抗病毒活性。FDA批准的藥物以粗體顯示。

表1. 目前正在開發的治療流感、RSV和MERS-CoV的新療法(臨床試驗)

總體而言，流感抗病毒藥物領域取得相對較大的進展。目前，三組藥物被批准用於治療流感，包括新批准的病毒聚合酶抑製劑baloxavir marboxil和僅一種批准用於RSV的多克隆帕利珠單抗。雖然有效，但這些藥物具有局限性，例如機會窗口減少，產生耐葯病毒的可能性和高成本（帕利珠單抗）。這凸顯了需要更多更好的抗病毒藥物來治療這些呼吸道感染。MERS-CoV是最近出現的人畜共患呼吸道感染，因此沒有批准用於治療的有效抗病毒藥物。最初的方法是遵循最近SARS爆發期間使用的抗病毒治療的例子，然而，使用廣譜抗病毒藥物的方法並不十分成功。

ABSTRACT

Emergence and re-emergence of respiratoryvirus infections represent a significant threat to global public health, asthey occur seasonally and less frequently (such as in the case of influenzavirus) as pandemic infections. Some of these viruses have been in the humanpopulation for centuries and others had recently emerged as a public healthproblem. Influenza viruses have been affecting the human population for a longtime now; however, their ability to rapidly evolve through antigenic drift andantigenic shift causes the emergence of new strains. A recent example of theseevents is the avian-origin H7N9 influenza virus outbreak currently undergoingin China. Human H7N9 influenza viruses are resistant to amantadines and somestrains are also resistant to neuraminidase inhibitors greatly limiting the optionsfor treatment. Respiratory syncytial virus (RSV) may cause a lower respiratorytract infection characterized by bronchiolitis and pneumonia mainly in childrenand the elderly. Infection with RSV can cause severe disease and even death,imposing a severe burden for pediatric and geriatric health systems worldwide.Treatment for RSV is mainly supportive since the only approved therapy, amonoclonal antibody, is recommended for prophylactic use in high-risk patients.The Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emergingrespiratory virus. The virus was first recognized in 2012 and it is associatedwith a lower respiratory tract disease that is more severe in patients withcomorbidities. No licensed vaccines or antivirals have been yet approved forthe treatment of MERS-CoV in humans. It is clear that the discovery anddevelopment of novel antivirals that can be used alone or in combination withexisting therapies to treat these important respiratory viral infections arecritical. In this review, we will describe some of the novel therapeuticscurrently under development for the treatment of these infections.

1. Mohammad Amin Behzadi and Victor H.Leyva-Grado*. Overview of Current Therapeutics and Novel Candidates AgainstInfluenza, Respiratory Syncytial Virus, and Middle East Respiratory SyndromeCoronavirus Infections. Front. Microbiol., 19 June 2019

https://doi.org/10.3389/fmicb.2019.01327

本期編輯：Annabella

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