A 2,5-Dihydroxybenzoic Acid-Gelatin Conjugate: The Synthesis, Antiviral Activity and Mechanism of Antiviral Action Against Two Alphaherpesviruses.
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.
Skryabin Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, Prospekt Nauki 5, Pushchino, Moscow Region 142290, Russia. ssl208@rambler.ru.
Alexander
A
Lisov
Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia. v_vrublevskaya@mail.ru.
Veronika
V
Vrublevskaya
Skryabin Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, Prospekt Nauki 5, Pushchino, Moscow Region 142290, Russia. zoyapozhid@rambler.ru.
Zoy
Z
Lisova
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.
Alexey
A
Leontievsky
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.
Oleg
O
Morenkov
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002460:Cell Line; D005780:Gelatin / Q000737:chemistry* / Q000378:metabolism; D005841:Gentisates / Q000138:chemical synthesis* / Q000494:pharmacology*; D007242:Herpesvirus 1, Bovine / Q000187:drug effects* / Q000502:physiology; D011558:Herpesvirus 1, Suid / Q000187:drug effects* / Q000502:physiology; D020128:Inhibitory Concentration 50; D053585:Virus Attachment / Q000187:drug effects
D000998:Antiviral Agents; D005841:Gentisates; D005780:Gelatin; C010925:2,5-dihydroxybenzoic acid
2,5-DHBA–gelatin conjugate; 2,5-dihydroxybezoic acid (2,5-DHBA); antiviral activity; bovine herpesvirus type 1; laccase; pseudorabies virus; virus adsorption