Influenza and Parainfluenza Antiviral Services
Influenza antiviral services at RetroVirox include a large menu of antiviral assays and characterization of inhibitors with multiple subtypes of human Influenza A and B strains grown in Madin Darby Canine Kidney (MDCK) cell lines and primary human respiratory epithelial cells. Readouts for influenza antiviral assays include high-throughput ELISA based nucleoprotein assays, reduction of the virus-induced cytopathic effect (“plaque assay”), neuraminidase enzymatic assays and hemagglutination assays. All influenza antiviral assays include positive controls with neuraminidase inhibitors or M2 blockers. Evaluation of cytotoxic effect of candidate inhibitors is also available. Antiviral assays include reports with calculation of 50 % inhibitory concentration (IC50), 90 % inhibitory concentration (IC90), 50 % cytotoxic concentration (CC50) and Selective (therapeutic) index (SI).
Assays designed to characterize the resistance profile and mechanism of action of candidate influenza inhibitors are also available. Candidate inhibitors may be tested for antiviral activity against virus resistant to two classes of anti-influenza compounds: neuraminidase inhibitors (oseltamivir and zanamivir) and adamantane derivatives (amantadine and rimantadine). Selection of influenza virus with resistance to a candidate antiviral is performed by passage of virus with escalating concentrations of antiviral. Virus with multiple resistance profiles may also be selected using drug combinations.
Combination studies to evaluate potential synergistic inhibition with known anti-influenza inhibitors are routinely performed at RetroVirox. Combination studies may be performed with influenza antivirals targeting M2, neuraminidase or with other experimental candidate inhibitors. Efficacy of combination of antivirals is evaluated as synergistic, additive or antagonistic using software packages including Prichard and Shipman MacSynergy II and Chou and Talalay median dose effect (Calcusyn).
We also offer anti-influenza discovery services with high-throughput screening of chemical libraries in 96, 384, and 1536-well formats. Experiments to evaluate antiviral mechanism of action with siRNA molecules, and to identify host factors using siRNA library screening can also be performed in high-throughput formats.
Evaluation of the neutralizing activity of influenza-reactive serum and influenza-specific monoclonal antibodies (neutralization assays) is routinely performed in our laboratories. These studies can be used to determine the in vitro antiviral efficacy of antibodies elicited in experimental anti-influenza vaccines. Neutralization assays against highly-pathogenic avian influenza strains are performed utilizing pseudotyped lentiviral particles coated with influenza hemagglutinin. Lentiviral vectors expressing H5N1 hemagglutinin from multiple clades are available for testing.
For additional information about Influenza antiviral services call us at (858) 677-9315 or contact us at antivirals@retrovirox.com
To see more information about antiviral assays offered against other viruses click on the following links:
Human Respiratory Syncytial Virus (HRSV)
Human Rhinovirus (HRV)
Hepatitis B Virus
Arenaviruses
