A 2,5-Dihydroxybenzoic Acid-Gelatin Conjugate: The Synthesis, Antiviral Activity and Mechanism of Antiviral Action Against Two Alphaherpesviruses.

Autor: Lisov A; Skryabin Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, Prospekt Nauki 5, Pushchino, Moscow Region 142290, Russia. ssl208@rambler.ru., Vrublevskaya V; Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia. v_vrublevskaya@mail.ru., Lisova Z; Skryabin Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, Prospekt Nauki 5, Pushchino, Moscow Region 142290, Russia. zoyapozhid@rambler.ru., Leontievsky A; Skryabin Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, Prospekt Nauki 5, Pushchino, Moscow Region 142290, Russia. leont@ibpm.pushchino.ru.; Pushchino State Institute of Life Sciences, ProspektNauki 3, Pushchino, Moscow Region 142290, Russia. leont@ibpm.pushchino.ru., Morenkov O; Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia. morenkov_o@mail.ru.; Pushchino State Institute of Life Sciences, ProspektNauki 3, Pushchino, Moscow Region 142290, Russia. morenkov_o@mail.ru.
Jazyk: angličtina
Zdroj: Viruses [Viruses] 2015 Oct 15; Vol. 7 (10), pp. 5343-60. Date of Electronic Publication: 2015 Oct 15.
DOI: 10.3390/v7102878
Abstrakt: Various natural and synthetic polyanionic polymers with different chemical structures are known to exhibit potent antiviral activity in vitro toward a variety of enveloped viruses and may be considered as promising therapeutic agents. A water-soluble conjugate of 2,5-dihydroxybezoic acid (2,5-DHBA) with gelatin was synthesized by laccase-catalyzed oxidation of 2,5-DHBA in the presence of gelatin, and its antiviral activity against pseudorabies virus (PRV) and bovine herpesvirus type 1 (BoHV-1), two members of the Alphaherpesvirinae subfamily, was studied. The conjugate produced no direct cytotoxic effect on cells, and did not inhibit cell growth at concentrations up to 1000 µg/mL. It exhibited potent antiviral activity against PRV (IC50, 1.5-15 µg/mL for different virus strains) and BoHV-1 (IC50, 0.5-0.7 µg/mL). When present during virus adsorption, the conjugate strongly inhibited the attachment of PRV and BoHV-1 to cells. The 2,5-DHBA-gelatin conjugate had no direct virucidal effect on the viruses and did not influence their penetration into cells, cell-to-cell spread, production of infectious virus particles in cells, and expression of PRV glycoproteins E and B. The results indicated that the 2,5-DHBA-gelatin conjugate strongly inhibits the adsorption of alphaherpesviruses to cells and can be a promising synthetic polymer for the development of antiviral formulations against alphaherpesvirus infections.
Databáze: MEDLINE