Therapeutic Activity of an Anti-Idiotypic Antibody-Derived Killer Peptide against Influenza A Virus Experimental Infection

Abstract

The in vitro and in vivo activities of a killer decapeptide (KP) against influenza A virus is described, and the mechanisms of action are suggested. KP represents the functional internal image of a yeast killer toxin that proved to exert antimicrobial and anti-human immunodeficiency virus type 1 (HIV-1) activities. Treatment with KP demonstrated a significant inhibitory activity on the replication of two strains of influenza A virus in different cell lines, as evaluated by hemagglutination, hemadsorption, and plaque assays. The complete inhibition of virus particle production and a marked reduction of the synthesis of viral proteins (membrane protein and hemagglutinin, in particular) were observed at a KP concentration of 4 g/ml. Moreover, KP administered intraperitoneally at a dose of 100 g/mice once a day for 10 days to influenza A/NWS/33 (H1N1) virus-infected mice improved the survival of the animals by 40% and significantly decreased the viral titers in their lungs. Overall, KP appears to be the first anti-idiotypic antibody-derived peptide that displays inhibitory activity and that has a potential therapeutic effect against pathogenic microorganisms, HIV-1, and influenza A virus by different mechanisms of action.

Antiviral Activity of Synthetic Peptides Derived from Physiological Proteins

“…Previous works have demonstrated an antiviral activity for KP against other enveloped viruses, such as HIV, by internalization of the chemokine receptor type 5 (CCR5) in susceptible cells, and human and avian influenza viruses, by reduction of viral protein synthesis, in particular M1 and HA [25, 26]. In both cases, a direct KP interaction with viral envelope has been excluded.…”

“…Several studies have already demonstrated a wide-spectrum antimicrobial activity by KP and some of the other peptides [21, 23, 32]. Yet, the antiviral activity of such peptides has not been investigated yet, with the exception of KP, which has been shown to inhibit HIV as well as human and avian influenza viruses [25, 26]. The results of the present work expand our knowledge on KP, showing that it drastically reduces HSV-1 viral yield, at both 50 μg/mL (99%) and 100 μg/mL (99.99%) (Fig.…”

“…It is a decapeptide, derived from the variable region of an anti-idiotypic Ab representing the functional internal image of a yeast killer toxin, endowed with a wide spectrum of antimicrobial activity [23, 24]. To date, KP has shown an outstanding activity against many different infectious agents, including HIV and influenza A viruses, through different mechanisms of action [25, 26]. Here, we expanded this issue, investigating the activity of KP against viruses with different morphology (enveloped vs. nonenveloped) and genome type (DNA vs. RNA).…”

Identification of 23-( S )-2-Amino-3-Phenylpropanoyl-Silybin as an Antiviral Agent for Influenza A Virus Infection In Vitro and In Vivo

“…Briefly, each lung was removed, weighed, and homogenized in minimal essential medium (MEM), and the viral titer was determined by the TCID 50 assay with MDCK cells. The number of wells showing a positive cytopathic effect was scored, and the titer (TCID 50 ) per milligram of lung tissue was calculated by standard procedures (28)(29)(30). All experimental procedures were approved by the Institutional Animal Care and Use Committee (IACUC) of Shantou University.…”

“…The mice were weighed daily for 21 days. Three mice per group were euthanized at day 6, when the virus titers in the lungs reached the maximum (28), and the viral titers in their lungs were analyzed. Briefly, each lung was removed, weighed, and homogenized in minimal essential medium (MEM), and the viral titer was determined by the TCID 50 assay with MDCK cells.…”