Novel Polyanions Inhibiting Replication of Influenza Viruses

Abstract

Novel sulfonated derivatives of poly(allylamine hydrochloride) (NSPAHs) and N-sulfonated chitosan (NSCH) have been synthesized, and their activity against influenza A and B viruses has been studied and compared with that of a series of carrageenans, marine polysaccharides of well-documented anti-influenza activity. NSPAHs were found to be nontoxic and very soluble in water, in contrast to gel-forming and thus generally poorly soluble carrageenans. In vitro and ex vivo studies using susceptible cells (Madin-Darby canine kidney epithelial cells and fully differentiated human airway epithelial cultures) demonstrated the antiviral effectiveness of NSPAHs. The activity of NSPAHs was proportional to the molecular mass of the chain and the degree of substitution of amino groups with sulfonate groups. Mechanistic studies showed that the NSPAHs and carrageenans inhibit influenza A and B virus assembly in the cell.

Synthetic sulfonated derivatives of poly(allylamine hydrochloride) as inhibitors of human metapneumovirus

“…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]. Surprisingly, we showed that new compounds share the mechanism of action with ι-carrageenan, and it is very different from previously proposed.…”

“…To determine the significance of the results obtained, Student t-test was used and P values < 0.05 were considered significant. Virus yields and virus titers are presented as normalized data, i.e., log reduction values (LRVs) [26] for easier comparison of the inhibitory effect between assays. LRV was calculated according to the following formula: LRV = log (c i /c 0 ) where c i is the number of viral RNA copies per milliliter in the sample treated with inhibitor and c 0 is the number of viral RNA copies per milliliter in control sample (untreated cells).…”

“…NSPAH-15-94 and NSPAH-65-96 were synthesized, analyzed and purified by dialysis as described before [26]. The purification process was carried out against deionized water for 1 week (molecular mass cutoff of 14 kDa).…”

“…To study the mechanism of action of tested polymers, a battery of functional assays were conducted as described before [26], with some modifications.…”

Antivirals against animal viruses

“…1.1), as the chitosan-conjugate bound to the viral hemagglutinin with high affinity and prevented viral attachment to the host. Ciejka et al recently synthesized new sulfonated derivatives of poly(allylamine hydrochloride) (CAS: 71550-12-4) and N-sulfonated chitosan and tested them against influenza A and B viruses [200]; the authors found that these novel molecules could inhibit influenza A and B virus assembly inside the host cell ( Fig. 1.1).…”