Table 1.

Agents for HRV/enterovirus prevention and treatment^b

Drug or therapy	Mechanism of action	Formulation	Study objective(s)a	Status	Result(s)	Comments	Source or reference(s)
Vapendavir	Capsid binder	Oral	Prevention of asthma exacerbations and reduction in URI symptom severity and duration	Phase 2b completed	Results not yet disclosed		ClinicalTrials.gov
Pleconaril	Capsid binder	Oral	Treatment of natural HRV colds	Phase 3 completed	1-day reduction in illness duration compared to placebo	U.S. FDA licensing withheld due to safety concerns	235, 236
Pirodavir	Capsid binder	Intranasal spray	Prevention of exptl HRV colds; treatment of exptl and natural HRV colds	Phase 3 completed	For prevention, reduced HRV infection rates when administered 6 times daily but not when given 3 times daily; for treatment, no difference in symptom severity or duration	Compound development discontinued	239, 240
Ruprintrivir	3C protease inhibitor	Intranasal spray	Prevention and treatment of exptl HRV infection	Phase 2 completed	For prevention, reduced frequency of positive viral cultures but not of colds; for treatment, reduced symptom severity by 33%	No effect on viral load or symptom severity in natural HRV infection (data not reported)	242
IFN-α2, IFN-β	Immunomodulatory and possible mediation of viral replication	Intranasal spray or drops	Prevention and treatment of exptl and natural HRV colds	Studies completed	For prevention, reduced HRV colds using IFN-α2, no benefit using IFN-β; for treatment, no difference in symptom severity or duration	Limited use as prophylaxis due to nasal irritation and nasal mucosal friability and bleeding	246, 274–278
Echinacea	Immunomodulatory	Oral	Prevention and treatment of exptl and natural HRV colds in adults and children	Phase 3 completed	For prevention, no reduction in HRV infection rates; for treatment, majority of studies showed no reduction in symptom severity or duration using various Echinacea extracts	EMA approved E. purpurea for treatment of respiratory tract infections in 2010	248–254
Vitamin C	Antioxidant	Oral	Prevention and treatment of natural colds in adults and children	Phase 3 completed	For prevention, no reduction in HRV colds; for treatment, modest reduction in symptom severity and duration	Treatment benefit may be limited to higher doses of vitamin C and to subjects undergoing brief physical stress	281
Zinc	Unknownc	Oral	Prevention and treatment of natural colds in adults and children	Phase 3 completed	For prevention, reduced cold incidence, school absenteeism, and antibiotic prescriptions in children; for treatment, reduced symptom severity and duration when taken within 24 h of symptom onset	Optimal dosage, formulation, and duration are unknown; side effects of zinc lozenges include bad taste and nausea	261
Antihistamines	H1 receptor inverse agonist	Oral	Treatment of exptl and natural HRV colds	Phase 3 completed	Reduced sneezing and rhinorrhea with no change in total symptom severity scores	Use limited by side effects of dry eyes, nose, and mouth; generally not recommended for treatment of HRV colds	263–265
Tremacamra	Recombinant sICAM-1	Intranasal spray or inhaled powder	Treatment of exptl HRV infection	Study completed	Reduced symptom severity and nasal mucus wt	Potential concerns of 6-times-daily administration affecting adherence and antibody response to sICAM-1; no further development currently reported	284
Enviroxime	Unknown; targets protein 3A	Intranasal spray or oral	Prevention of exptl HRV infection; treatment of exptl and natural HRV colds	Phase 2 completed	For prevention, no reduction in HRV infection; for treatment, no difference in symptom severity or wt of nasal secretions	Oral formulation with gastrointestinal side effects; lack of response to intranasal spray may be due to inconsistent drug levels	285–288

^aAll agents were evaluated in adults only unless otherwise specified.

^bHRV, human rhinovirus; FDA, Food and Drug Administration; ICAM-1, intercellular adhesion molecule 1; sICAM-1, soluble ICAM-1; IFN, interferon; EMA, European Medicines Agency.

^cSee the text.