Antiviral therapeutic approaches for human rhinovirus infections

Casanova, Victor; Sousa, Filipa H; Stevens, Craig; Barlow, Peter G

Neutralizing antibodies RV ssRNA genome is contained within an icosahedral protein capsid comprised of four structural proteins; three are surface exposed (VP1, VP2 and VP3), and VP4 is buried [141] . RV-specific neutralizing antibodies have been developed against epitopes found on VP proteins that aim to block virus-receptor interaction, stabilize the capsid preventing viral uncoating, or cause conformational changes in the capsid inducing premature genome release [142, 143, 144] . Other studies have shown that antibodies raised against VP4, specifically the N terminus, had RV neutralizing activity and, indeed, may be a promising target for therapeutic development [145, 146] . Another approach has been to develop antibodies that bind to the host cell receptors, thereby blocking entry of RV. Targeting ICAM-1 in transgenic mice engineered to overexpress extracellular domains 1 and 2 of human ICAM-1 has been shown to prevent the entry of two major groups of RV, RV16 and RV14. Reduced cellular inflammation, proinflammatory cytokine production and virus load was also observed in this model [147] . However, targeting and blockage of other receptors used by minor group RV, such as the low-density lipoprotein (LDL) receptor, has proved elusive. This is also the case in the context of the development of a universal 'anti-RV' antibody, which is problematic due to the antigenic diversity of circulating RV. Thus, there remain significant challenges associated with the identification of new antigenic variants and the fact that around 90% of RV serotypes cannot bind to the murine ICAM-1 receptor.