Abstract
Human metapneumovirus (hMPV) is a widely distributed pathogen responsible for acute upper and lower respiratory infections of varying severity. Previously, we reported that N-sulfonated derivatives of poly(allylamine hydrochloride) (NSPAHs) efficiently inhibit replication of the influenza virus in vitro and ex vivo. Here, we show a dose dependent inhibition of hMPV infection by NSPAHs in LLC-MK2 cells. The results showed strong antiviral properties of NSPAHs. While the activity of NSPAHs is comparable to those of carrageenans, they show better physicochemical properties and may be delivered at high concentrations. The functional assays showed that tested polymers block hMPV release from infected cells and, consequently, constrain virus spread. Moreover, further studies on viruses utilizing different egress mechanisms suggest that observed antiviral effect depend on selective inhibition of viruses budding from the cell surface.
Highlights
Human metapneumovirus is associated with acute infections of the respiratory tract, with increased severity in children, infants, elderly, and immunocompromised patients [1,2,3,4]. hMPV was identified in 2001 in the Netherlands [5] and sorted to the Pneumoviridae family
Previous studies have shown that natural polysaccharides containing sulfonate groups efficiently inhibit infections caused by viruses employing heparan sulfate (HS) during cell entry [12,13,14,15,16,17,18,19] and it was proposed that carrageenans inhibit the attachment of the hMPV to HS by interacting with the F protein [19]
In our previous report we showed that N-sulfonated derivatives of poly(allylamine) hydrochloride (NSPAHs) effectively inhibit influenza virus in vitro and ex vivo by inhibition of virion release from infected cells [26]
Summary
Human metapneumovirus (hMPV) is associated with acute infections of the respiratory tract, with increased severity in children, infants, elderly, and immunocompromised patients [1,2,3,4]. hMPV was identified in 2001 in the Netherlands [5] and sorted to the Pneumoviridae family. Previous studies have shown that natural polysaccharides containing sulfonate groups efficiently inhibit infections caused by viruses employing HS during cell entry [12,13,14,15,16,17,18,19] and it was proposed that carrageenans inhibit the attachment of the hMPV to HS by interacting with the F protein [19].
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