isirv Antiviral Group
Other Respiratory Viruses
Very few approved antivirals exist for respiratory viruses other than influenza, but on-going discovery work and clinical studies may change clinical practice for certain viruses in the near future. Several agents, such as ribavirin and interferons, have relatively broad spectra of activity, whereas others are virus type specific. Several agents are available on compassionate use basis or, like ribavirin and cidofovir, are used for off-label indications.
Examples of approved and investigational agents in clinical testing:
Respiratory syncytial virus (RSV)
Prevention of RSV infection using passive immunoprophylaxis has been studied with both polyclonal and monoclonal antibodies in children. Palivizumab prophylaxis is licensed for use in children less than 2 years old but is not therapeutically effective and immunoprophylaxis with palivizumab (15mg/kg/dose monthly during the RSV season) is costly.
In high-risk patients, including hematopoietic stem cell or lung transplant recipients, preemptive ribavirin treatment by various routes (aerosol, oral, intravenous) at the stage of upper respiratory tract infection, alone or in combination with standard intravenous or RSV-specific immunoglobulins, is a commonly employed clinical strategy to limit progression to pneumonia and also to treat established lower respiratory illness: available data suggest the combination may be superior to either agent alone. A polyclonal anti-RSV immunoglobulin designated RI-001 is in advanced testing in transplant patients with RSV upper respiratory tract illness, and is available for compassionate use from ADMA Biologics.
A small interfering RNA (siRNA) targeting the N gene of RSV, designated ALN-RSV01, has shown inhibitory activity in pre-clinical studies and when administered topically in volunteers with experimentally induced RSV. A phase II trial in lung transplant recipients with RSV found lower illness scores and decreased risk of new or progressive bronchiolitis obliterans syndrome; a larger trial is in progress.
Parainfluenza virus (PIV) and human metapneumovirus (hMPV)
Ribavirin by various routes, with or without IV immunoglobulins, has been used to treat PIV and hMPV infections in transplant recipients with uncertain benefits. DAS181, a recombinant fusion sialidase, removes surface sialic acid residues required by influenza and PIV to infect cells. Topical DAS181 is inhibitory for PIV in vitro and in a cotton rat model and has been used with possible benefit in a few immunocompromised hosts with serious PIV illness.
Cidofovir, a monophosphate nucleotide analog of cytosine, is inhibitory for a range of DNA viruses, including all adenoviruses, and has been used intravenously for treatment of adenovirus viremia and invasive infections in transplant patients. CMX001, an orally bioavailable lipid conjugate of cidofovir, provides greater ease of administration and much better renal tolerability than cidofovir. Oral CMX001 showed antiviral effects in some highly immunocompromised hosts who failed or could not tolerate cidofovir, and further clinical studies are in progress.
Human rhinoviruses (HRVs)
One oral capsid-binding agent, termed BTA-798, has shown activity in volunteers with experimental HRV infection, and a phase II study of asthmatic patients with colds to see if early treatment can reduce exacerbations has recently been completed, although the results have not been presented. Several types of natural and recombinant interferon-α, given intranasally, are protective against HRV colds but associated with local irritation during prolonged use. A different type of interferon, inhaled Interferon-β1a, designated SNG001, is in clinical development to treat rhinovirus and possibly other respiratory virus infections in asthmatic patients.