Table 2.

Summary of Mechanism and Evidence for Key Anti-RV Therapies

Therapeutic	Proposed Mechanism of Action	Existing Evidence
Azithromycin	Induction of IFN-β and IFN-λ in host response to RV	Indirect evidence only via studies in asthma exacerbations, where long term prophylaxis of 420 patients as part of a randomised placebo-controlled trial reduced the number of exacerbations and improved quality of life.65 In a separate study in acute exacerbations, no benefit was demonstrated.66
Budesonide	Reduction in pro-inflammatory cytokines, protection of host cells from cytotoxicity	No evidence from human clinical trials to date.
Gemcitabine	Inhibition of viral proliferation and viral RNA synthesis	No evidence from human clinical trials to date.
Host defence peptides	Exogenous bolstering of the host innate immune response	No evidence from human clinical trials to date.
IFN-β	Exogenous correction of impaired IFN response in asthma and COPD patients	A randomised placebo-controlled trial of 147 people with asthma tested inhaled IFN-β within 24 hours of a naturally occurring cold symptoms. It failed to meet its primary endpoint, likely due to less severe than expected exacerbations.67
Itraconazole	Reduced viral replication and suppression of inflammation	No evidence from human clinical trials to date.
Nitric oxide	Direct inhibition of rhinovirus replication and inhibition of pro-inflammatory cytokine production	No evidence from human clinical trials to date.
Pirodavir	Binding to viral capsid protein, inducing conformational change and preventing adsorption and RNA uncoating	100 patients were enrolled across three randomised placebo-controlled studies assessing pirodavir as prophylaxis against experimental viral challenge of rhinovirus strains, and demonstrated a reduction in symptoms. 32 patients enrolled in a randomised placebo-controlled study treated after inoculation did not demonstrate the same benefit.68 A later randomised controlled trial of 98 patients in the context of naturally occurring colds did not demonstrate a clinical benefit.69
Pleconaril	Binding to and impairing critical viral capsid functions of attachment and RNA uncoating	Combined analysis of two randomised placebo-controlled trials in a total of 1363 patients symptomatic with naturally occurring picornavirus infections demonstrated a reduction in time to alleviation of illness, although more side effects were experienced in the active treatment arm.70
Quercetin	Reduces RV replication and host cytokine response.	No evidence from human clinical trials to date.
Ribavirin	Direct: impairing viral RNA synthesis and increasing viral mutation rates. Indirect: upregulation of host immune response.	Efficacy demonstrated prophylactically in vitro.71,72 In vivo work is limited to a case series of 4 patients with hypogammaglobulinaemia where it was used in combination with IFN-α.73
Rupintrivir	Inhibits the 3C protease by bonding to the active site on the viral protease	No evidence from human clinical trials to date.
Tremacamra	Blocking viral entry and reduction in pro-inflammatory cytokines	198 adults were randomised across four trials to receive the molecule in either pre- or post- experimental rhinovirus inoculation studies. A reduction in symptom scores, clinical colds and rhinorrhoea was demonstrated.74
Vapendavir	Binding to viral capsid protein, inducing conformational change and preventing adsorption and RNA uncoating	455 asthmatic adults with naturally occurring (presumed) rhinovirus infection in a randomised double-blind placebo-controlled trial received vapendavir for 6 days after symptoms started. Although the trial reported a significant reduction in cold symptoms at 2 to 4 days post infection, the primary endpoint was not met.75
Vitamin D	Supporting innate immune system via increased cathelicidin and IFN stimulated genes	A large recent meta-analysis of 43 trials and 48,488 participants demonstrated that vitamin D supplementation reduces the incidence of acute respiratory infections.76