Inhibition of Herpes Simplex Virus Types 1 and 2 In Vitro Infection by Sulfated Derivatives of Escherichia coli K5 Polysaccharide

Abstract

Herpes simplex virus type 1 (HSV-1) and HSV-2 are neurotropic viruses and common human pathogens causing major public health problems such as genital herpes, a sexually transmitted disease also correlated with increased transmission and replication of human immunodeficiency virus type 1 (HIV-1). Therefore, compounds capable of blocking HIV-1, HSV-1, and HSV-2 transmission represent candidate microbicides with a potential added value over that of molecules acting selectively against either infection. We report here that sulfated derivatives of the Escherichia coli K5 polysaccharide, structurally highly similar to heparin and previously shown to inhibit HIV-1 entry and replication in vitro, also exert suppressive activities against both HSV-1 and HSV-2 infections. In particular, the N,O-sulfated [K5-N,OS(H)] and O-sulfated epimerized [Epi-K5-OS(H)] forms inhibited the infection of

Inhibition of Herpes Simplex Virus Type 1 and Type 2 Infections by Peptide-Derivatized Dendrimers

“…From this perspective, agents like SB105 and SB105_A10, which prevent attachment to target cells, may be most advantageous. The suitability of this strategy is demonstrated by numerous negatively charged polyanions that in recent years have been selected for development as candidate microbicides, as they bind HSV envelope components and block virion attachment and entry into target cells (28). Of these, dendrimers and dendrimer-like molecules have recently been generated with surfaces formed of negative charges and screened for potential antiherpesvirus activities (12,31).…”

Heparan Sulfate Proteoglycans: A Multifaceted Target for Novel Approaches in Antiviral Drug Discovery

“…It can be chemically sulfated in defined N and/or O positions, resulting in the generation of K5 derivatives with different charge distribution, devoid of anticoagulant activity and endowed with specific binding capacities. In previous works, K5 sulfated derivatives have been demonstrated to be devoid of toxic effects and endowed with an interesting multitarget activity, being able to inhibit infection by different viruses, including HSV, HPV, RSV, citomegalovirus, dengue virus, and HIV [16][17][18][19][20][21] HSPG-binding compounds are an heterogeneous group of polycationic compounds that bind to negatively charged sulfated groups of HS chains, masking HSPGs to virus and preventing their attachment to the cell (Figure 1). In the field of antiviral drug discovery, polycationic HSPG-binding molecules has received so far little consideration compared to polyanionic HSPG-antagonists.…”

Highly Sulfated K5 Escherichia coli Polysaccharide Derivatives Inhibit Respiratory Syncytial Virus Infectivity in Cell Lines and Human Tracheal-Bronchial Histocultures

“…In effect, K5 sulfated derivatives have been demonstrated to be endowed with inhibitory activity against different viruses, including herpes simplex virus (HSV) (38), human papilloma virus (HPV) (39), cytomegalovirus (CMV) (40), dengue virus (29), and HIV (37). Regarding this last virus, K5 polysaccharides have been demonstrated to classically act as antimicrobial agents, likely binding to the basic gp120 protein but also binding to and neutralizing other HIV proteins released by infected cells (i.e., Tat and p17) that contribute to HIV dissemination and to the onset of AIDS-associated infections (30,45).…”

“…Besides the case of RSV, HSPGs have also been demonstrated to act as attachment receptors for human immunodeficiency virus (HIV) (31), herpes simplex virus (HSV) (32), human papillomavirus (HPV) (33), human cytomegalovirus (HCMV) (34), dengue virus (35), and filoviruses (36); accordingly, several anti-HSPG strategies have been attempted for all of these viruses (29,37,38,39,40). Despite that fact that this huge amount of in vitro experimentation initially provided promising results, few polyanionic, heparin-like compounds progressed to clinical trial for different viral diseases (41,42,43).…”