An anti-dengue and anti-herpetic polysulfated fraction isolated from the coenocytic green seaweed Caulerpa cupressoides inhibits thrombin generation in vitro

Abstract

The antiviral potency of Caulerpa cupressoides (Chlorophyta) sulfated polysaccharidic fractions (Cc-SP1→3) associated with thrombin generation (TG) assay is unknown. This study analyzed the structure of Cc-SP1 and its effects against herpes viruses (HSV-1 and HSV-2), dengue-virus (DENV-1), human-metapneumovirus (HMPV) and adenovirus (AdV) in Vero and mosquito C6/36 cell-lines and as inhibitor of TG in 60-fold diluted human plasma using continuous system. Infrared analysis indicated ulvan containing 11% sulfate, 40.16% total sugars and 6% uronic acid. Procedures of agarose/polyacrylamide gels electrophoresis revealed two major components presenting sulfate and non SPs, with molecular dispersion ranging from 8 to > 100 kDa, respectively, as confirmed by gel permeation chromatography. Cc-SP1 did not cause cytotoxicity up to 1000 μg mL^-1 and was more effective inhibitor of DENV-1 (96%, 0.35 μg mL^-1) compared with HSV-1 (90%, 27 μg mL^-1) and HSV-2 (99.9%, 0.9 μg mL^-1) in Vero cell-line, whose selectivity indexes were > 714, > 9.2 and > 131, respectively, but was inactive against HMPV, AdV and C6/36 cell-line using plate reduction assay. Cc-SP1 required concentration 20.8-fold higher of SPs than heparin for abolishes intrinsically TG, but at concentrations so far the anti-HSV-1. Therefore, TG assay provides data to guide studies of Cc-SP1 on anticoagulant/antiviral effects.