The enzymatic depolymerization of fucoidans from brown algae allowed the production of their standardized derivatives with different biological activities. This work aimed to compare the antiviral activities of native (FeF) and modified with enzyme (FeHMP) fucoidans from F. evanescens. The cytotoxicity and antiviral activities of the FeF and FeHMP against herpes viruses (HSV-1, HSV-2), enterovirus (ECHO-1), and human immunodeficiency virus (HIV-1) in Vero and human MT-4 cell lines were examined by methylthiazolyltetrazolium bromide (MTT) and cytopathic effect (CPE) reduction assays, respectively. The efficacy of fucoidans in vivo was evaluated in the outbred mice model of vaginitis caused by HSV-2. We have shown that both FeF and FeHMP significantly inhibited virus-induced CPE in vitro and were more effective against HSV. FeF exhibited antiviral activity against HSV-2 with a selective index (SI) > 40, and FeHMP with SI ˃ 20, when they were added before virus infection or at the early stages of the HSV-2 lifecycle. Furthermore, in vivo studies showed that after intraperitoneal administration (10 mg/kg), both FeF and FeHMP protected mice from lethal intravaginal HSV-2 infection to approximately the same degree (44–56%). Thus, FeF and FeHMP have comparable potency against several DNA and RNA viruses, allowing us to consider the studied fucoidans as promising broad-spectrum antivirals.
The effect of carrageenans and fucoidans on the activity of Hantavirus is studied. It has been found that among carrageenans a significant antiviral effect is exerted by the ι-type, which decreases the viral titer by 2.5 log focus forming units per mL; among fucoidans, by a preparation from Laminaria cichorioides, which reduces the number of infected cells from 27.0 to 5.3 after pretreatment of both the macrophage culture and Hantavirus. The antiviral effect of fucoidan from Laminaria japonica is shown to grow in direct proportion to the increase of dose of the preparation.
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 β3 to prevent virus–cell interactions. The relatively small size of these sites of interactions explains the higher anti-AMRV activity of the FeLMP fraction.
Four 1,4-naphthoquinone dithioglucoside derivatives based on natural polyhydroxy-1,4-naphthoquinones were synthesized. These thioglucosides were screened for their antiradical and antiviral activity in vitro. Antiradical activity of tested compounds was determined by the 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay. The anti-herpes simplex virus type 1 (anti-HSV-1) activity of thioglucosides was analyzed by the cytopathic effect inhibition assay and mode of antiviral action was determined by the addition of the tested compounds to uninfected cells, to the virus prior to infection, or to herpes-infected cells. Most effective inhibition of HSV-1 replication was observed at pretreatment of virus by the compounds (direct virucidal effect). The dithioglucoside conjugate with the single β-OH group and lipophilic ethyl substituent in naphthoquinone core showed the greatest antiviral activity.
л.н. яшина 1 , н.а. сметанникова 1 , Г.Г. компанец 2 , н.и. Здановская 3 , л.и. иванов 3 молеКулярная эПидемиология ПатогеннЫх хантавируСов на дальнем воСтоКе роССии, 2015-2018 гг.
There are presented data on group cases of hemorrhagic fever with renal syndrome (HFRS) in the foci of distribution of mouselike rodents - the carriers of pathogenic genotypes of hantaviruses. A relationship between HFRS incidence and the period of acute manifestations of infection in rodents has been revealed. According to detection by RT-PCR specific RNA on substrates of environment there were designated the possible factors of transmission of the agent.
In an unresponsive model (adult albino mice), Hantavirus infection caused only obvious immunomorphological changes in the organs. Prolonged preheat stress in the hantavirus-infected animals promoted inapparent infection and morphological manifestations of induced secondary immunodeficiency that was responsible for the manifestation of an infectious process in some animals.
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