GFP Labelled Parainfluenza Virus 5

Influenza viruses are highly contagious and a major cause of respiratory illness in humans, potentially causing severe epidemics and occasional pandemics. Papaverine, a non-narcotic alkaloid used to treat heart disease, impotence, and psychosis, has been found to be a potent inhibitor of multiple influenza virus strains. Kinetic studies have shown that papaverine inhibits influenza virus infection at a late stage in the viral life cycle. Papaverine, a well-known phosphodiesterase inhibitor, also alters the mitogen-activated protein kinase (MAPK) pathway by downregulating the phosphorylation of MEK and extracellular signal-regulated kinase (ERK). Therefore, modulation of host cell signaling pathways by papaverine may be associated with nuclear retention of vRNPs and reduction of influenza virus titers. Interestingly, papaverine also inhibited infection with the paramyxoviruses parainfluenza virus 5 (PIV5), human parainfluenza virus 3 (HPIV3), and respiratory syncytial virus (RSV). The researchers suggest that papaverine could be a potential candidate for an antiviral agent against multiple influenza and paramyxoviruses.

Here, the effects of papaverine treatment on cells infected with the paramyxoviruses PIV5, RSV, and HPIV3 and the rhabdovirus VSV were studied. Viruses were grown in the presence of varying concentrations of papaverine or DMSO and then harvested 3 days postinfection (dpi) for PIV5, HPIV3, and RSV infection, and 2 dpi for VSV infection. Viral titers of PIV5, HPIV3, and RSV were reduced when grown in the presence of papaverine (Figure 1A). However, VSV showed no inhibition of viral titers after papaverine treatment, even at a concentration of 150 μM. The results were confirmed by infecting CV-1 cells with green fluorescent protein (GFP) labelled PIV5 or GFP labelled VSV. GFP fluorescence of PIV5-GFP-infected cells treated with papaverine decreased proportionally, but VSV-GFP fluorescence levels remained unchanged (Figure 1B). Cell viability of CV-1 and HEp2 cells infected with HPIV3 and RSV, respectively, in the presence of papaverine was also observed using light microscopy. In both cases, cytopathic effects were observed after viral infection and were significantly reduced when the virus was grown in the indicated concentrations of papaverine (Figure 1B).

Figure 1. Antiviral effect of papaverine on paramyxoviruses PIV5, RSV, and HPIV3 and rhabdovirus VSV. (Aggarwal M, et al., 2020)