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

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.

A review on gentisic acid as a plant derived phenolic acid and metabolite of aspirin: Comprehensive pharmacology, toxicology, and some pharmaceutical aspects

“…The cytotoxicity and acute toxicity of these new compounds were negligible(Mikolasch et al, 2007).A conjugate of gelatin and GA was synthesized by laccasecatalyzed oxidation of GA in the presence of gelatin, and it has antiviral activities against pseudorabies virus and bovine herpes virus type 1, two members of the alpha herpes virinae subfamily. GAgelatin 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 pseudorabies virus glycoproteins E and B, but it strongly inhibits the adsorption of alpha herpes viruses to cells so, can be a promising synthetic polymer for the development of antiviral formulations against alpha herpes virus infections(Lisov, Vrublevskaya, Lisova, Leontievsky, & Morenkov, 2015).…”

Antiviral activities of ellagitannins against bovine herpesvirus-1, suid alphaherpesvirus-1 and caprine herpesvirus-1

“…Antiviral activity against this virus, as well as against BoHV-1, has also been shown by lambda-carrageenan prepared from red seaweed (Diogo et al, 2015). Moreover, Lisov et al (2015) demonstrated that 2,5-dihydrobenzoic acidgelatin conjugate has an anti-BoHV-1 effect and suggested that this agent would also be effective against other alphaherpesvirus subfamily members due to the similar mode of entry into the host cells. Some studies on the spread and replication of herpesviruses have been conducted using natural substances found in many foods that a person consumes daily.…”

Biopolymeric nano/microspheres for selective and reversible adsorption of coronaviruses

“…Influenza A virus particles may be adsorbed by the carbohydrate-functionalized chitosan filaments [25]. The application of proteins and peptides as adsorbents has been also reported [26,27].…”

“…Adsorbents for various viruses have been described including alfaherpesviruses (pseudorabies virus (PrV) and bovine herpesvirus 1 (BHV-1) [28]), influenza A virus [25], porcine parvovirus (PPV) [26], sindbis virus (SINV) [25], retroviruses [13], poliovirus [29], and foamy virus [8]. Importantly, the only adsorbent for coronaviruses that has been tested so far, based on clay minerals, could adsorb bovine coronavirus.…”