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Viruses 2015, 7(10), 5343-5360; doi:10.3390/v7102878

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

1
Skryabin Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, Prospekt Nauki 5, Pushchino, Moscow Region 142290, Russia
2
Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia
3
Pushchino State Institute of Life Sciences, ProspektNauki 3, Pushchino, Moscow Region 142290, Russia
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Curt Hagedorn
Received: 28 May 2015 / Revised: 24 September 2015 / Accepted: 8 October 2015 / Published: 15 October 2015
(This article belongs to the Section Antivirals & Vaccines)
View Full-Text   |   Download PDF [3442 KB, uploaded 23 October 2015]   |  

Abstract

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. View Full-Text
Keywords: laccase; 2,5-dihydroxybezoic acid (2,5-DHBA); 2,5-DHBA–gelatin conjugate; pseudorabies virus; bovine herpesvirus type 1; antiviral activity; virus adsorption laccase; 2,5-dihydroxybezoic acid (2,5-DHBA); 2,5-DHBA–gelatin conjugate; pseudorabies virus; bovine herpesvirus type 1; antiviral activity; virus adsorption
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Lisov, A.; Vrublevskaya, V.; Lisova, Z.; Leontievsky, A.; Morenkov, O. A 2,5-Dihydroxybenzoic Acid–Gelatin Conjugate: The Synthesis, Antiviral Activity and Mechanism of Antiviral Action Against Two Alphaherpesviruses. Viruses 2015, 7, 5343-5360.

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