Table 29.3.
Preventive and therapeutic compounds affecting HRV infections
| Therapeutic agent | Primary role | Effect | Evaluation | Reference |
|---|---|---|---|---|
| IFN-α | Elicit cellular antiviral effects | Decreased shedding if administered within 24 h | Toxicity | [471–475] |
| Pirodavir (R77975) | Capsid binder | Intranasal formulation useful against both HRV antiviral groups; three to six doses per day | Variable efficacy, irritation, and mucosal bleeding | [471, 476, 477] |
| WIN54954 | Capsid binder | Broadly active in mice | Reduced efficacy in humans | [471, 478] |
| WIN56291 | Capsid binder | Active against HRV-C15 | Effect only in organ culture so far | [161, 479] [63] |
| Pleconaril (WIN63843) | Capsid binder | Resolved symptoms 1–2 days earlier than placebo. Some types are resistant | FDA issued “not approvable” letter because of side effects | [471, 477] |
| Vapendavir (BTA798) | Capsid binder | Potent binding in animal models | Good bioavailability and safety profile in animals. Phase IIa trial complete | [477, 480] |
| Rupintrivir (AG-7088) | 3C protease inhibitor | Insignificant impact | Discontinued | [470, 471, 481, 482] |
| Enviroxime | Replication inhibitor | Potent anti-replicative activity in vitro | Side effects in vivo | [406, 472] |
| Tremacamra | Soluble ICAM-1 molecule | Could reduce experimental cold symptoms and the quantity of virus shed if administration occurs before or after inoculation but prior to the development of symptoms | [483] | |
| Tiotropium | Anticholinergic agent (bronchodilator) | Reduced HRV-B14 viral load and RNA levels, decreased susceptibility of cells, reduced ICAM-1 mRNA levels and IL-1β, IL-6, and IL-8 protein levels in culture | No obvious change to cell viability in culture | [484] |
| Levofloxacin | Quinolone antibiotic | Reduced HRV-B14 and HRV-A15 viral load (major group HRVs; not the minor group virus, HRV-A2) and RNA levels, decreased susceptibility of cells, reduced ICAM-1 mRNA levels and IL1β, IL6, and IL8 protein levels in culture | No obvious cytotoxicity in culture | [485] |
| Pellino-1 | Regulates IRAK-1 | Controlled primary epithelial cell non-IFN response to HRV-A1; knockdown by siRNA reduced CXCL8 in primary BECs | Did not cause unwanted shutdown of an antiviral response. Target unknown | [486] |
| Azithromycin | Macrolide antibiotic | Significantly increased IFNs and ISG mRNA and proteins resulting from HRV-A1 and HRV-A16 infection in primary BECs. Reduced HRV replication and release | Modest effect in cell culture at relatively high concentration. Mechanism unknown | [487] |
FDA US Food and Drug Administration, ICAM-1 intercellular adhesion molecule 1, IFN interferon, IRAK-1 interleukin-1 receptor-associated kinase-1, BEC bronchial epithelial cells