Glycosaminoglycans (GAGs) are negatively charged check details linear polysaccharides that are typically sulfated and include

chondroitin sulfate (CS) and heparan sulfate (HS). They represent a repertoire of complex natural glycans that are localized within extracellular matrices and on cell surfaces, and exhibit heterogeneous structures that allow them to bind to a wide range of protein partners such as adhesion molecules, chemokines, cytokines, growth factors, and matrix proteins [18]. Thus, GAGs play important roles in many biologic processes, which have profound physiological consequences that include cell signaling, inflammation, angiogenesis, and coagulation

[18, 19]. Many viruses employ GAGs as primary entry factors that facilitate the infection of the host cell. These include DENV, HCMV, HCV, HIV, HSV, MV, RSV, and others [20–32]. Interactions of viral glycoproteins with GAGs are usually thought to increase the frequency of initial attachment of viral particles to the target cell surface. They, in turn, enable subsequent higher affinity binding with virus-specific entry receptors that promote virus entry. The importance of GAGs in facilitating viral infections has been demonstrated by using soluble heparin or GAG-deficient cell lines to block the entry of several viruses [20–31]. In our previous study, we identified chebulagic acid (CHLA) and punicalagin (PUG) (Figure 1), two hydrolyzable tannins Ro-3306 nmr isolated from Terminalia chebula Retz., (T. chebula) as inhibitors of HSV type 1 (HSV-1) entry and spread [33]. We demonstrated that the two structurally-related compounds mediated Flavopiridol (Alvocidib) their antiviral activities by targeting HSV-1 viral glycoproteins that interact with cell surface GAGs. Taking note of the fact that many viruses employ GAGs to initially bind to the host cell, and based on evidence that CHLA and PUG may act as GAG-competitors, we explored the antiviral-Angiogenesis inhibitor potential of these two tannins against a number of viruses known to interact

with GAGs. Viral models included DENV, HCMV, HCV, MV, and RSV (Table 1). Many of the diseases associated with these viruses lack preventative vaccines and/or drug treatment options [1–4, 13, 34–36]. Indeed, both CHLA and PUG efficiently inhibited entry and spread of these viruses to varying degrees. We suggest that CHLA and PUG have potential as novel cost-effective and broad-spectrum antivirals for controlling emerging/recurring infections by viruses that engage host cell surface GAGs. Figure 1 Structures of chebulagic acid (CHLA) and punicalagin (PUG). The chemical structures of the two hydrolyzable tannins under study, chebulagic acid (CHLA) and punicalagin (PUG), are presented.