Nucleosides for the treatment of respiratory RNA virus infections

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

Rhinoviruses are thought to be the cause of up to twothirds of what is termed the common cold, worldwide. Children tend to experience up to 12 of these infections, or colds, per year, while this incidence drops in adults to just 2-3 per year. 25 There are three distinct species of rhinovirus, RV-A, RV-B, and RV-C, each of which infects humans at different periods throughout the year. 26 Symptoms include cough, fever, sneezing, nasal congestion, sore throat, fever, and headache and usually last 7-10 days after an initial 48-h viral incubation. 27 In addition to the three rhinoviruses, four enterovirus species result in disease in humans, EV-A, EV-B, EV-C, and EV-D, while EV-E through EV-H, and EV-J affect non-human hosts. 28, 29 Enteroviruses differ from rhinoviruses in that while rhinoviruses are limited to the respiratory airways, enteroviruses infect a wide range of cell types. They result in a large array of complications associated with the respiratory, gastrointestinal, and central nervous systems. Manifestations of enterovirus infection range from a febrile cold to encephalitis, pneumonia, viral meningitis, and even death. 30 Although EV-C and EV-D are the principal enteroviruses that cause respiratory illness, EV-A also includes EV71. EV71 causes hand-foot-and-mouth disease, a highly contagious pathogen in children that mainly results in a maculopapular rash, blisters on the limbs, and ulcers in the mouth. 31 EV71 is most prevalent in the summer months and tends to be more ubiquitous in tropical zones of the globe. In rare cases of severe EV71 infection, respiratory illness can lead to pulmonary edema, hemorrhage, and lung failure. 32