Anti-respiratory syncytial virus and anti-herpes simplex virus activity of chemically engineered sulfated fucans from Cystoseira indica.

Seaweed polysaccharides, particularly sulfated ones, exhibited potent antiviral activity against a wide variety of enveloped viruses, such as herpes simplex virus and respiratory viruses. Different mechanisms of action were suggested, which may range from preventing infection to intracellular antiviral activity, at different stages of the viral cycle. Herein, we generated two chemically engineered sulfated fucans (C303 and C304) from Cystoseira indica by an amalgamated extraction-sulfation procedure using chlorosulfonic acid-pyridine/N,N-dimethylformamide and sulfur trioxide-pyridine/N,N-dimethylformamide reagents, respectively. These compounds exhibited activity against HSV-1 and RSV with 50 % inhibitory concentration values in the range of 0.75-2.5 µg/mL and low cytotoxicity at concentrations up to 500 µg/mL. The antiviral activities of chemically sulfated fucans (C303 and C304) were higher than the water (C301) and CaCl2 extracted (C302) polysaccharides. Compound C303 had a (1,3)-linked fucan backbone and was branched. Sulfates were present at positions C-2, C-4, and C-2,4 of Fucp, and C-6 of Galp residues of this polymer. Compound C304 had a comparable structure but with more sulfates at C-4 of Fucp residue. Both C303 and C304 were potent antiviral candidates, acting in a dose-dependent manner on the adsorption and other intracellular stages of HSV-1 and RSV replication, in vitro.

Topical formulations containing Trichilia catigua extract as therapeutic options for a genital and an acyclovir-resistant strain of herpes recurrent infection.

Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infect, respectively, 67% and 13% of the world population, most commonly causing mild symptoms, such as blisters/ulcers. However, severe conditions such as keratitis, encephalitis, and systemic infections may occur, generally associated with the patient's immunological condition. Although Acyclovir® (ACV) and its analogs are the reference drugs for herpetic infections, the number of ACV-resistant HSV infections is growing exponentially. Therefore, new natural products' bioactive compounds have been studied to develop novel effective anti-herpetics. Trichilia catigua is a plant widely used in traditional medicine, including the treatment of skin diseases and sexual infections. In our study, 16 extracts from the bark of T. catigua, obtained with different solvents and their combinations, were evaluated against HSV-1 AR and HSV-2, respectively, ACV resistance and genital strains in vitro. The extracts with the highest selectivity index were used to prepare new topical anti-herpetic formulations and confirmed in vivo. Two new topical formulations were suggested to treat cutaneous and genital herpetic recurrent lesions. The cytotoxicity and antiviral activity were tested using the MTT method. The cytotoxic (CC50) and inhibitory (IC50) concentrations of 50% and the selectivity index (SI: CC50/IC50) were determined. Tc12, Tc13, and Tc16 were added to the formulations. Infected BALB/c mice were treated for 8 days, and the severity of the herpetic lesions was analyzed daily. All CEs showed a CC50 value ranging from 143 to 400 µg/mL, except for Tc3 and Tc10. Tc12, Tc13, and Tc16 showed the best SI in the 0 h, virucidal, and adsorption inhibition assays. In the in vivo test against HSV-1 AR, the infected animals treated with creams were statistically different from the infected non-treated animals and similar to ACV-treated mice. In HSV-2-infected genitalia, similar effects were found for Tc13 and Tc16 gels. The present study demonstrated that extracts from the bark of T. catigua, traditionally used in folk medicine, are a valuable source of active compounds with anti-herpetic activity. The extracts showed a virucidal mechanism of action and prevented the initial stages of viral replication. The cutaneous and genital infections were strongly inhibited by the Tc12, Tc13, and Tc16 extracts. New topical therapeutic alternatives using Trichilia catigua extracts are suggested for patients infected with ACV-resistant strains of HSV.