title: Effects of macromolecular crowding on the inhibition of virus assembly and virus-cell receptor recognition.
abstract: Biological fluids contain a very high total concentration of macromolecules that leads to volume exclusion by one molecule to another. Theory and experiment have shown that this condition, termed macromolecular crowding, can have significant effects on molecular recognition. However, the influence of molecular crowding on recognition events involving virus particles, and their inhibition by antiviral compounds, is virtually unexplored. Among these processes, capsid self-assembly during viral morphogenesis and capsid-cell receptor recognition during virus entry into cells are receiving increasing attention as targets for the development of new antiviral drugs. In this study, we have analyzed the effect of macromolecular crowding on the inhibition of these two processes by peptides. Macromolecular crowding led to a significant reduction in the inhibitory activity of: 1), a capsid-binding peptide and a small capsid protein domain that interfere with assembly of the human immunodeficiency virus capsid, and 2), a RGD-containing peptide able to block the interaction between foot-and-mouth disease virus and receptor molecules on the host cell membrane (in this case, the effect was dependent on the conditions used). The results, discussed in the light of macromolecular crowding theory, are relevant for a quantitative understanding of molecular recognition processes during virus infection and its inhibition.
authors.affiliation: Centro de Biología Molecular "Severo Ochoa" (Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid), Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Rincón
authors.affiliation: Centro de Biología Molecular "Severo Ochoa" (Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid), Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Bocanegra
authors.affiliation: Centro de Biología Molecular "Severo Ochoa" (Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid), Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Rodríguez-Huete
authors.affiliation: Centro de Investigaciones Biológicas (Consejo Superior de Investigaciones Científicas), Madrid, Spain.
authors.forename: Germán
authors.initials: G
authors.lastname: Rivas
authors.affiliation: Centro de Biología Molecular "Severo Ochoa" (Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid), Universidad Autónoma de Madrid, Madrid, Spain. Electronic address: mgarcia@cbm.uam.es.
authors.forename: Mauricio G
authors.initials: MG
authors.lastname: Mateu
mesh_terms: D000818:Animals; D002213:Capsid / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D029544:Foot-and-Mouth Disease Virus / Q000187:drug effects* / Q000472:pathogenicity; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D046911:Macromolecular Substances / Q000378:metabolism / Q000633:toxicity*; D009842:Oligopeptides / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011991:Receptors, Virus / Q000378:metabolism*; D019065:Virus Assembly / Q000187:drug effects*
chemical_list: D046911:Macromolecular Substances; D009842:Oligopeptides; D010455:Peptides; D011991:Receptors, Virus; C047981:arginyl-glycyl-aspartic acid