Antiviral Peptides as Anti-Influenza Agents

Abstract

Influenza viruses represent a leading cause of high morbidity and mortality worldwide. Approaches for fighting flu are seasonal vaccines and some antiviral drugs. The development of the seasonal flu vaccine requires a great deal of effort, as careful studies are needed to select the strains to be included in each year’s vaccine. Antiviral drugs available against Influenza virus infections have certain limitations due to the increased resistance rate and negative side effects. The highly mutative nature of these viruses leads to the emergence of new antigenic variants, against which the urgent development of new approaches for antiviral therapy is needed. Among these approaches, one of the emerging new fields of “peptide-based therapies” against Influenza viruses is being explored and looks promising. This review describes the recent findings on the antiviral activity, mechanism of action and therapeutic capability of antiviral peptides that bind HA, NA, PB1, and M2 as a means of countering Influenza virus infection.

Targeting the Human Influenza a Virus: The Methods, Limitations, and Pitfalls of Virtual Screening for Drug-like Candidates Including Scaffold Hopping and Compound Profiling

“…One 24-residue-long oligopeptide binds NA with a micromolar inhibition constant (Ki = 0.29 mM), and a much smaller octapeptide was designed as a strong nanomolar binder at the active site where oseltamivir appears, showing one-digit micromolar inhibition activity in the cell tests. In this context, AAmol, with only two amide bonds, is an even smaller H1N1 NA inhibitor than all the other reported peptides (4 to 24 residues long) [ 38 ].…”

“…Its molecular mass is 337 Daltons; with an estimated log P = 1.2; a polar surface area of 183 Å 2 ; a non-PSA of 441.9 Å 2 ; a HBA = 4; HBD = 2; highly flexible conformations (12 rotatable bonds); and a commercial vendor: Chembridge # 6429718. A recent review outlined the fundamental principles concerning peptide inhibitors against the flu [ 38 ]. One 24-residue-long oligopeptide binds NA with a micromolar inhibition constant (Ki = 0.29 mM), and a much smaller octapeptide was designed as a strong nanomolar binder at the active site where oseltamivir appears, showing one-digit micromolar inhibition activity in the cell tests.…”

Synthetic Frog-Derived-like Peptides: A New Weapon against Emerging and Potential Zoonotic Viruses

“…Another peptide resulting from the skin secretion of amphibians is urumin, secreted by Hydrophylax bahuvistara . As demonstrated by Agamennone et al, this peptide inhibited influenza virus infection by interacting with hemagglutinin [ 22 ]. Recently, we demonstrated that Temporin L, belonging to the Ranidae family and secreted by Rana temporaria , not only had antibacterial activity, but was also capable of inhibiting viral infection.…”

Rational Design of Novel Peptidomimetics against Influenza A Virus: Biological and Computational Studies

“…Antivirals are an alternative approach to combating the various subtypes of influenza viruses [ 5 ]. Antiviral compounds approved by the Food and Drug Administration (FDA) for flu treatment can be classified into three groups: the neuroaminidase (NA) inhibitors oseltamivir phosphate, zanamivir, peramivir, and laninamivir octanoate hydrate; the M2 ion channel blockers amantadine and rimantadine; and the cap-dependent endonuclease protein inhibitor baloxavir marboxil [ 6 , 7 , 8 , 9 , 10 ]. However, the emerging threat of new pandemic influenza strains spreading through the human population and the rise of resistance to licensed drugs have focused research into developing new treatments for influenza viruses [ 11 , 12 , 13 , 14 ].…”