title: Inhibition of influenza A virus infection in vitro by peptides designed in silico.
abstract: Influenza A viruses are enveloped, segmented negative single-stranded RNA viruses, capable of causing severe human respiratory infections. Currently, only two types of drugs are used to treat influenza A infections, the M2 H(+) ion channel blockers (amantadine and rimantadine) and the neuraminidase inhibitors (NAI) (oseltamivir and zanamivir). Moreover, the emergence of drug-resistant influenza A virus strains has emphasized the need to develop new antiviral agents to complement or replace the existing drugs. Influenza A virus has on the surface a glycoprotein named hemagglutinin (HA) which due to its important role in the initial stage of infection: receptor binding and fusion activities of viral and endosomal membranes, is a potential target for new antiviral drugs. In this work we designed nine peptides using several bioinformatics tools. These peptides were derived from the HA1 and HA2 subunits of influenza A HA with the aim to inhibit influenza A virus infection. The peptides were synthetized and their antiviral activity was tested in vitro against several influenza A viral strains: Puerto Rico/916/34 (H1N1), (H1N1)pdm09, swine (H1N1) and avian (H5N2). We found these peptides were able to inhibit the influenza A viral strains tested, without showing any cytotoxic effect. By docking studies we found evidence that all the peptides were capable to bind to the viral HA, principally to important regions on the viral HA stalk, thus could prevent the HA conformational changes required to carry out its membranes fusion activity.
authors.affiliation: Laboratorio de Virología, Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Carpio y Plan de Ayala S/N, Casco de Santo Tomás, México D.F., México.
authors.forename: Rogelio
authors.initials: R
authors.lastname: López-Martínez
authors.forename: G Lizbeth
authors.initials: GL
authors.lastname: Ramírez-Salinas
authors.forename: José
authors.initials: J
authors.lastname: Correa-Basurto
authors.forename: Blanca L
authors.initials: BL
authors.lastname: Barrón
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D001665:Binding Sites; D002460:Cell Line; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D017124:Conserved Sequence; D015195:Drug Design; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects* / Q000502:physiology*; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D011487:Protein Conformation; D021122:Protein Subunits; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D010455:Peptides; D021122:Protein Subunits