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.
Highlights
Influenza A viruses are enveloped, segmented negative single-stranded RNA viruses, belonging to the Orthomyxoviridae family, capable of causing several respiratory diseases in humans, varying from upper acute respiratory infections to severe diseases like pneumonia [1]
HA1 and HA2 subunits showed a highly conserved amino acid sequence of approximately 50 and 40 amino acids length, located at the N-t and C-t end of the HA1 subunit, respectively (Figures 1A, 1B); and 80 amino acids length at the N-t of the HA2 subunit. Once we detected these conserved regions in the HA subunits, they were submit analyzed for several physicochemical parameters to design the antiviral peptides (AVPs)
Regions of the glycoproteins with these physiochemical properties have been used for designing antiviral peptides [53,30]
Summary
Influenza A viruses are enveloped, segmented negative single-stranded RNA viruses, belonging to the Orthomyxoviridae family, capable of causing several respiratory diseases in humans, varying from upper acute respiratory infections to severe diseases like pneumonia [1]. Influenza A virus infection initiates with the attachment of the viral surface glycoprotein hemagglutinin (HA) to sialic acid receptors located on the cell surface. The HA is synthesized as a polypeptide HA0 precursor, which contains a signal sequence, a proteolytic cleavage site, a hydrophobic sequence known as the fusion peptide, and a transmembrane anchor domain in the carboxy-terminal end, followed by a cytoplasmic tail. The distal domain is made only by the HA1 polypeptide and contains the sialic acid-receptor binding site (RBS) and a vestigial esterase (VES) subdomain [5]. The stalk region is mainly formed by the HA2 polypeptide, which contains the Fusion subdomain (F) and the N- and C- terminal segments of the HA1 polypeptide (Ffusion subdomain) [6,7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
