Nucleosides for the treatment of respiratory RNA virus infections

Jordan, Paul C; Stevens, Sarah K; Deval, Jerome

Respiratory viral infections are a global health concern caused by dozens of different types of viruses. The respiratory diseases resulting from these viral infections represent one of the main causes of death in developing countries. 1 A more thorough understanding of respiratory viruses, their epidemiology, as well as medical impact on the communities they affect will delineate the path toward eventual treatments and future abatement of the illnesses. While symptoms of many respiratory viruses are similar, the viruses themselves are characteristically unique. Categorically, viruses are grouped based on similarities such as the nature of their nucleic acid genome, envelope presence, overall size, and even capsid uniformity. 2 This review focuses on the following families of RNA viruses: Orthomyxoviridae, Paramyxoviridae and Pneumoviridae, Picornaviridae, and Coronaviridae. Orthomyxoviridae comprise negative (-) sense singlestranded (ss) RNA viruses that are segmented, enveloped, and includes the influenza viruses (see Table 1 ). Paramyxoviridae and Pneumoviridae are also (-)ssRNA viruses, but are non-segmented and enveloped, and include parainfluenza virus (PIV), human respiratory syncytial virus (RSV), and human metapneumovirus (HMPV). The Picornaviridae family, which contains positive (þ)ssRNA viruses are non-enveloped; the key members include the rhinoviruses and enteroviruses. Lastly, the Coronaviridae are (þ)ssRNA enveloped viruses, which include, chiefly, human coronavirus (HCoV), and severe acute respiratory syndrome (SARS)-associated and Middle Eastern respiratory syndrome (MERS) CoV. 3 Young children, the elderly, and patients with compromised cardiac, pulmonary, or immune systems are at greatest risk for serious disease associated with these RNA virus respiratory infections. In a 10-year study, over 85% of acute respiratory viral infections in critically ill children admitted to a pediatric intensive care unit were caused by either a picornavirus, RSV, PIV, or HMPV (see Figure 1 ). 4 Other DNA viruses such as adenovirus can be the source of respiratory infections but will not be discussed here.