RESUMEN
Herpes simplex virus (HSV) infections, the incidence of which is still widespread throughout the world, are actualizing the search and development of new, more effective antiherpetic drugs. The development of multifunctional drug delivery systems, including liposome-based ones, has become a relevant and attractive concept in nanotechnology. The ability of complexes of κ- and Σ-carrageenans (CRGs)-sulfated polysaccharides of red algae, with echinochrome A (Ech), as well as the liposomal form of the Σ-CRG/Ech complex-to inhibit different stages of HSV-1 infection in Vero cells was studied. By quantum chemical calculations, it was shown that CRG forms stable complexes with Ech. We have shown that complexes of κ-CRG/Ech and Σ-CRG/Ech exhibit highest virucidal activity with a selectivity index (SI) of 270 and 350, respectively, and inhibition of virus-cell interaction (SI of 83 and 32, respectively). The liposomal form of the Σ-CRG/Ech complex after virus adsorption and penetration to cells effectively reduced the HSV-1 plaque formation. The virus-inhibiting activity of the liposomal form of the Σ-CRG/Ech complex was three times higher than that of the Σ-CRG/Ech complex itself. Obtaining CRGs/Ech complexes and their liposomal forms can become the basis of a successful strategy for the development of promising antiherpetic drugs.
Asunto(s)
Liposomas , Polisacáridos , Animales , Chlorocebus aethiops , Carragenina/farmacología , Carragenina/química , Células Vero , Polisacáridos/química , Antivirales/farmacología , Antivirales/químicaRESUMEN
The structural diversity and unique physicochemical properties of sulphated polysaccharides of red algae carrageenans (CRGs), to a great extent, determine the wide range of their antiviral properties. This work aimed to compare the antiviral activities of different structural types of CRGs: against herpes simplex virus type 1 (HSV-1) and enterovirus (ECHO-1). We found that CRGs significantly increased the resistance of Vero cells to virus infection (preventive effect), directly affected virus particles (virucidal effect), inhibited the attachment and penetration of virus to cells, and were more effective against HSV-1. CRG1 showed the highest virucidal effect on HSV-1 particles with a selective index (SI) of 100. CRG2 exhibited the highest antiviral activity by inhibiting HSV-1 and ECHO-1 plaque formation, with a SI of 110 and 59, respectively, when it was added before virus infection. CRG2 also significantly reduced the attachment of HSV-1 and ECHO-1 to cells compared to other CRGs. It was shown by molecular docking that tetrasaccharides-CRGs are able to bind with the HSV-1 surface glycoprotein, gD, to prevent virus-cell interactions. The revealed differences in the effect of CRGs on different stages of the lifecycle of the viruses are apparently related to the structural features of the investigated compounds.
Asunto(s)
Antivirales/farmacología , Carragenina/farmacología , Rhodophyta , Animales , Antivirales/química , Organismos Acuáticos , Carragenina/química , Chlorocebus aethiops , Enterovirus/efectos de los fármacos , Herpesvirus Humano 1/efectos de los fármacos , Humanos , Simulación del Acoplamiento Molecular , Relación Estructura-Actividad , Células Vero/efectos de los fármacosRESUMEN
The Hantaan orthohantavirus (genovariant Amur-AMRV) is a rodent-borne zoonotic virus; it is the causative agent of haemorrhagic fever with renal syndrome in humans. The currently limited therapeutic options require the development of effective anti-orthohantavirus drugs. The ability of native fucoidan from Fucus evanescens (FeF) and its enzymatically prepared high-molecular-weight (FeHMP) and low-molecular-weight (FeLMP) fractions to inhibit different stages of AMRV infection in Vero cells was studied. The structures of derivatives obtained were determined using nuclear magnetic resonance (NMR) spectroscopy. We found that fucoidan and its derivatives exhibited significant antiviral activity by affecting the early stages of the AMRV lifecycle, notably virus attachment and penetration. The FeHMP and FeLMP fractions showed the highest anti-adsorption activity by inhibiting AMRV focus formation, with a selective index (SI) > 110; FeF had an SI of ~70. The FeLMP fraction showed a greater virucidal effect compared with FeF and the FeHMP fraction. It was shown by molecular docking that 2O-sulphated fucotetrasaccharide, a main component of the FeLMP fraction, is able to bind with the AMRV envelope glycoproteins Gn/Gc and with integrin ß3 to prevent virus-cell interactions. The relatively small size of these sites of interactions explains the higher anti-AMRV activity of the FeLMP fraction.
Asunto(s)
Antivirales/farmacología , Orthohantavirus/efectos de los fármacos , Phaeophyceae , Polisacáridos/farmacología , Animales , Antivirales/química , Organismos Acuáticos , Humanos , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Peso Molecular , Polisacáridos/químicaRESUMEN
Herpes simplex virus type 1 (HSV-1) is one of the most prevalent pathogens worldwide requiring the search for new candidates for the creation of antiherpetic drugs. The ability of sea urchin spinochromes-echinochrome A (EchA) and its aminated analogues, echinamines A (EamA) and B (EamB)-to inhibit different stages of HSV-1 infection in Vero cells and to reduce the virus-induced production of reactive oxygen species (ROS) was studied. We found that spinochromes exhibited maximum antiviral activity when HSV-1 was pretreated with these compounds, which indicated the direct effect of spinochromes on HSV-1 particles. EamB and EamA both showed the highest virucidal activity by inhibiting the HSV-1 plaque formation, with a selectivity index (SI) of 80.6 and 50.3, respectively, and a reduction in HSV-1 attachment to cells (SI of 8.5 and 5.8, respectively). EamA and EamB considerably suppressed the early induction of ROS due to the virus infection. The ability of the tested compounds to directly bind to the surface glycoprotein, gD, of HSV-1 was established in silico. The dock score of EchA, EamA, and EamB was -4.75, -5.09, and -5.19 kcal/mol, respectively, which correlated with the SI of the virucidal action of these compounds and explained their ability to suppress the attachment and penetration of the virus into the cells.
Asunto(s)
Antivirales/farmacología , Herpesvirus Humano 1/efectos de los fármacos , Naftoquinonas/farmacología , Erizos de Mar/metabolismo , Animales , Antivirales/aislamiento & purificación , Chlorocebus aethiops , Herpesvirus Humano 1/crecimiento & desarrollo , Herpesvirus Humano 1/metabolismo , Interacciones Huésped-Patógeno , Simulación del Acoplamiento Molecular , Naftoquinonas/aislamiento & purificación , Especies Reactivas de Oxígeno/metabolismo , Células Vero , Proteínas del Envoltorio Viral/metabolismo , Ensayo de Placa Viral , Acoplamiento Viral/efectos de los fármacos , Internalización del Virus/efectos de los fármacosRESUMEN
The aim of this study was to examine the in vitro antioxidant and antiviral activities of echinochrome A and echinochrome-based antioxidant composition against tick-borne encephalitis virus (TBEV) and herpes simplex virus type 1 (HSV-1). The antioxidant composition, which is a mixture of echinochrome A, ascorbic acid, and α-tocopherol (5:5:1), showed higher antioxidant and antiviral effects than echinochrome A. We suppose that echinochrome A and its composition can both directly affect virus particles and indirectly enhance antioxidant defense mechanisms in the hosting cell. The obtained results allow considering the echinochrome A and the composition of antioxidants on its basis as the promising agents with the both antioxidant and antiviral activities.