title: A simple model to predict the effectiveness of molecules that block attachment of human rhinoviruses and other viruses.
abstract: The binding of viruses to cell surfaces is often mediated by cell surface receptors. The use of soluble receptors, such as intracellular adhesion molecule-1 (ICAM-1) for human rhinovirus (HRV), CD4 for human immunodeficiency virus (HIV), and CR2 for Epstein-Barr virus, for in vivo antiviral therapy is under serious investigation. A number of synthetic compounds that affect HRV attachment and uncoating (termed WIN compounds) are also being studied. However, the mechanism behind the dose-response effect of these agents in preventing infection has not been clearly demonstrated. In addition to simple blocking (by receptors) or inactivation of binding sites (by WIN compounds) on the virus surface, other mechanisms of inhibition have been proposed and demonstrated, including cooperative inactivation of neighboring sites, receptor-induced viral attachment protein (VAP) shedding, virus particle inactivation, and inhibition of multivalent virus binding. We present a simple mathematical model to predict the effect of these molecules on virus infection by incorporating only the blocking or site inactivation step of the blocking molecule and its resulting effect on attachment. The ability of the model to reproduce the response of a virus to a dose of blocking molecules is used to distinguish the role of blockers in inhibiting attachment from the other mechanisms of viral inactivation that have been proposed. The model includes both the reversible attachment of the virus to its cellular receptor and to soluble receptors or synthetic molecules (blockers).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: School of Chemical Engineering, Cornell University, Ithaca, New York 14853, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Wickham
authors.forename: M L
authors.initials: ML
authors.lastname: Shuler
authors.forename: D A
authors.initials: DA
authors.lastname: Hammer
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006678:HIV / Q000187:drug effects* / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008561:Membrane Fusion / Q000187:drug effects*; D008954:Models, Biological; D011991:Receptors, Virus / Q000187:drug effects*; D012229:Rhinovirus / Q000187:drug effects* / Q000502:physiology
chemical_list: D000998:Antiviral Agents; D011991:Receptors, Virus