Comparison of Antiviral Activity between Monomeric, Dimeric and Oligomeric Proanthocyanidins against Human Norovirus Surrogates

Introduction: Proanthocyanidins (PACs) are dimers, oligomers, and polymers of catechins linked between carbons, C4 and C8 (or C6). Polymerized PACs in blueberries contain B-type linkages, with different profiles and amounts than cranberries that contain A-type linkages. B-type PAC can be converted to A-type PAC by radical oxidation that influences their bioactivity. Both B-type and A-type PAC reportedly have antiviral activity against human noroviral surrogates, that needs further understanding to prevent or treat human norovirus infections.

Purpose: The objectives of this study were to compare the antiviral activity between monomeric catechin monohydrate, procyanidin B2, B-type PAC from blueberries (B-PAC) and A-type PAC from cranberries (C-PAC) on the infectivity of human norovirus surrogates, feline calicivirus (FCV-F9) and murine norovirus (MNV-1), at 37°C.

Methods: FCV-F9 and MNV-1 at 5 log plaque forming units (PFU)/ml were treated with equal amounts of 0.5 or 1 mg/ml catechin monohydrate, procyanidin B2, blueberry PAC, cranberry PAC or phosphate buffered saline (pH 7.2, control) at 37°C over 6 h. Infectivity was determined using plaque assays and data from triplicate experiments were statistically analyzed.

Results: Monomeric catechins at 1 mg/ml reduced both viruses to undetectable levels only after 24 h. Procyanidin B2 at 1 mg/ml reduced FCV-F9 to undetectable levels within 6 h and MNV-1 by only 1.29 log PFU/ml after 24 h. Polymeric B-PAC at 1 mg/ml reduced both FCV-F9 and MNV-1 to undetectable levels within 3 h, while polymeric C-PAC at 0.6 mg/ml reportedly caused 5.02 and 2.95-log reduction of FCV-F9 and MNV-1, respectively, within 1 h.

Significance: Overall, polymeric catechins (PACs) showed a higher and faster antiviral effect compared to monomeric catechins. This study provides insights between the antiviral activity of different structural polyphenols that should help in the design of appropriate preventive and anti-noroviral therapies from natural sources.