Antiviral Properties of Alginate-Based Biomaterials: Promising Antiviral Agents against SARS-CoV-2.

The COVID-19 pandemic has made it essential to explore alternative antiviral materials. Alginate is a biodegradable, renewable, biocompatible, water-soluble and antiviral biopolymer with many potential biomedical applications. In this regard, this review shows 17 types of viruses that have been tested in contact with alginate and its related biomaterials. Most of these studies show that alginate-based materials possess little or no toxicity and are able to inhibit a wide variety of viruses affecting different organisms: in humans by the human immunodeficiency virus type 1, the hepatitis A, B, and C viruses, Sindbis virus, herpes simplex virus type 1 and 2, poliovirus type 1, rabies virus, rubella virus, and the influenza virus; in mice by the murine norovirus; in bacteria by the T4 coliphage, and in plants by the tobacco mosaic virus and the potato virus X. Many of these are enveloped positive-sense single-stranded RNA viruses, like SARS-CoV-2, which render alginate-based materials highly promising in the COVID-19 pandemic.

Inhibition of in vitro hematopoiesis by hepatitis A virus.

Inoculation of human bone marrow with hepatitis A virus (HAV) resulted in a dose- and duration-of-incubation-dependent suppression of hematopoietic progenitor (CFU-GM, BFU-E, CFU-Mix) growth in vitro. Monocytic progenitors appeared to be least affected. While HAV inactivation by heat or beta-propiolactone and neutralization by specific antibodies completely abrogated hematopoietic inhibition, depletion of adherent bone marrow cells, and enrichment of progenitors did not alter the pattern of suppression, which also seemed to be independent of HuIFN-alpha, -beta, -gamma, and TNF. These findings support the concept that direct infection of progenitor cells by HAV may be responsible for hematologic changes commonly seen during early phases of infectious hepatitis and possibly for some cases of bone marrow failure.

Effect of isoflavans and isoflavenes on the infection of Frp/3 cells by hepatitis A virus.

The effect of 6,4'-dichloroflavan and of isoflavan and isoflavene derivatives on hepatitis A virus (HAV) infection in a monkey cell line (Frp/3 cells) was studied. These compounds were not virucidal and had no measurable effect on the adsorption of virus to the cells at 0 degrees C, whereas they exerted an inhibitory effect on viral antigen synthesis when incubated with the infected cells during HAV multiplication. Among the substances tested, 6,4'-dichloroflavan and 6,4'-dichloroisoflavan showed the highest activity. These compounds are postulated to interact with an early stage (penetration and/or uncoating) of HAV infection.

Antiviral activity of recombinant interferon-alpha on hepatitis A virus replication in human liver cells.

Human recombinant interferon-alpha (IFN-alpha) was assayed for its antiviral effect on hepatitis A virus (HAV) replication in the human hepatoma cell line PLC/PRF/5. IFN-alpha resulted in concentration-dependent reduction of HAV antigen expression and HAV replication. IFN-alpha had a prophylactic effect, but was still effective when it was added after the infection, even at the end of the first replication cycle. An important increase in 2',5'-oligoadenylate synthetase activity in the IFN-treated human liver cells was observed. The antiviral effect of IFN-alpha could be attributed to the induction of this enzyme. Moreover we have shown that IFN-alpha and glycyrrhizin were synergistic in their antiviral actions against HAV. IFN-alpha emerged, from the present study, as a promising candidate for chemotherapy of severe forms of hepatitis A.

Studies on mechanism of action of glycyrrhizin against hepatitis A virus replication in vitro.

Glycyrrhizin (GL) achieved a concentration-dependent inhibition of the replication of hepatitis A virus (HAV) in PLC/PRF/5 cells. GL has been shown to inhibit an early stage of the HAV replication. GL was not virucidal and had no measurable effect on the adsorption of [3H]uridine-labelled virions to cells. GL inhibited HAV penetration of the plasma membrane as measured by the amount of infective virus no longer neutralizable by specific antibody over time.

Influence of twenty potentially antiviral substances on in vitro multiplication of hepatitis A virus.

A multiwell tissue culture system was developed to study the influence of various substances on hepatitis A virus (HAV) propagation. A panel of 20 substances of different structure types, each with known effect against at least some viruses, was studied at a concentration of 100 microM. Three substances showed reproducible inhibition. The strongest inhibitor, arabinosylcytosine, also produced cytotoxic changes in cells down to a concentration of 1 microM, and its effect was considered as nonspecific. Amantadine and ribavirin showed a moderate effect at 100 microM. A stronger inhibition was seen at 250 and 500 microM, doses that are toxic and impractical for clinical use. Although no promising candidates for antiviral treatment of hepatitis A have emerged from the present study, the assay model described here would seem useful in the screening of substances with inhibitory effects on HAV.

Inactivation of human immunodeficiency virus type 1, hepatitis A virus, respiratory syncytial virus, vaccinia virus, herpes simplex virus type 1, and poliovirus type 2 by hydrogen peroxide gas plasma sterilization.

BACKGROUND: Studies were conducted to determine the capability of a hydrogen peroxide gas plasma sterilization process to inactivate several types of viruses. Six test agents were used: HIV type 1, human hepatitis A virus, respiratory syncytial virus, vaccinia, herpes simplex virus type 1, and poliovirus type 2. METHODS: The test viruses were suspended in cell culture medium and dried on the bottom of sterile glass petri dishes. The inoculated dishes were processed in the hydrogen peroxide gas plasma system for half the normal sterilization cycle time. Four inoculated carriers for each virus were used in two separate half cycles. Infectivity of the test viruses and cytotoxicity to the indicator cell lines were assayed. RESULTS: The hydrogen peroxide gas plasma sterilization process produced inactivation of the six viral test agents under these experimental conditions. The reduction in viral titers ranged from 2.5 log10 to 5.5 log10, a 99.68% to 99.999% decrease. CONCLUSIONS: These results clearly demonstrate the virucidal effectiveness of the hydrogen peroxide gas plasma sterilization process against both lipid and nonlipid viruses.

Disinfection of human enteric viruses on fomites.

The virucidal action of several commercially available disinfectant preparations was assayed against hepatitis A virus and human rotavirus dried on polystyrene. Overall, the level of virus disinfection achieved was very poor, usually inducing less than 3 log titre reduction. Suspension tests performed with the same disinfectants showed different virus inactivation rates, thus failing to provide a reliable indication of the actual virus disinfection on fomites. In our studies, bacteriophages of Bacteroides fragilis proved to be a simple, cheap and reliable screening tool for the evaluation of virus disinfection on non-porous surfaces. The same conclusion cannot be drawn for poliovirus.

Conformational changes in the hepatitis A virus capsid in response to acidic conditions.

Low pH values encountered during uptake of viruses by receptor-mediated endocytosis have been shown to expose hydrophobic residues of many viruses and result in viral conformational changes leading to uncoating of the viral genome. An assay for hydrophobicity utilising the non-ionic detergent Triton X-114 was established, making use of metabolically-labelled hepatitis A virus (HAV). In this assay, hydrophilic proteins interact with the aqueous (buffer) phase, while hydrophobic proteins interact with the Triton (detergent) phase. HAV particles interact with the aqueous phase at neutral pH, whereas, under acidic conditions, HAV was found predominantly in the detergent phase. This indicates that the capsid of HAV undergoes conformational changes rendering the particle more hydrophobic under acidic conditions. A further two conformational changes were found in HAV on exposure to low pH, as detected by changes in buoyant density in CsCl gradients. These were maturation of provirions to virions and the formation of dense particles. These results may have implications for uncoating of the HAV RNA genome, and these conformational changes could represent intermediates in the viral uncoating process.

Effect of glutaraldehyde on the antigenicity and infectivity of hepatitis A virus.

The effect of glutaraldehyde on the antigenicity and infectivity of hepatitis A virus (HAV) was examined. The CF 53 strain, adapted to human hepatoma PLC/PRF/5 cells, was treated with glutaraldehyde using three different concentrations, 0.02, 0.10, and 0.50%, for various periods of time, 3, 10, and 30 min, respectively. After the virucidal assays, glutaraldehyde and HAV were separated by gel filtration, then the antigen (radioimmunoassay) titer and the infectivity titer were determined. The greatest antigen titer reduction was about 80% after 30 min using 0.10% glutaraldehyde and within only 3 min using 0.50% glutaraldehyde. Glutaraldehyde is an effective disinfectant against HAV: the infectious virus titer decreased by more than 3 log10 after 30 min using 0.10% glutaraldehyde and within only 3 min using 0.50% glutaraldehyde. Statistical studies showed that the decrease of antigen or infectious virus titer was affected by both glutaraldehyde concentration and exposure time.

Influence of polyions on the early steps of enterovirus infection.

The influence of electric charged molecules on the early phases of enterovirus infection was studied in order to select antiviral compounds able to prevent viral attachment. The effect of different polyelectrolytes on the multiplication of coxsackie virus B3, echovirus 6 and hepatitis A virus was investigated in susceptible cells by adding the drug before, during or after the viral adsorption period. Among polyanions, the polysaccharides heparin and dextran sulfate inhibited viral infectivity, dextran sulfate being the most effective mainly towards hepatitis A virus infection. DEAE-dextran and protamine sulfate, generally recognized as enhancers of infectivity of naked and enveloped viruses, exhibited an inhibitory effect towards the three picornaviruses tested. Only in the case of hepatitis A did DEAE-dextran slightly improve viral antigen synthesis. The inhibitory effect shown by compounds belonging to positive and negative polyions suggests that the electric charge is not sufficient by itself to explain the antiviral activity of these drugs.

[Effect of various chlorine doses on inactivation of hepatitis A virus in water]. / Vliianie razlichnykh doz khlora na inaktivatsiiu virusa gepatita A v vode.

Bound chlorine in doses 0.8-1.2 mg/l does not inactivate viruses in water. Chlorine can be active against hepatitis A viruses in concentration not less than 4.2 mg/l with the virion content in water 10(5)/ml and at least 20 min exposure.

Effect of cellular function inhibitors on the infection of Frp/3 cells by hepatitis A virus.

The effect of some cellular function inhibitors on hepatitis A virus (HAV) adsorption and on the successive events of infection in a monkey cell line (Frp/3 cells) was investigated. Treatments of Frp/3 cells with colcemide, vinblastine and cytochalasin D, which affect cytoskeleton organization, indicated that neither microtubules nor microfilaments play an important role in the early events of HAV infection. Monensin, which acts as an ionophore on intracellular vesicle compartments inhibited HAV infection probably at the uncoating step. Inhibition of viral replication to a different degree was observed with both inhibitors of oxidative phosphorylation, such as dinitrophenol and sodium azide, and with an inhibitor of glycolysis, 2-deoxy-D-glucose. However, none of these compounds significantly affected the early steps of infection, thus demonstrating that HAV replication is largely dependent upon cell energy.

Methisoprinol-effect on the replication cycle of human hepatitis A virus.

The antiviral activity of methisoprinol was investigated under different conditions using a strain of hepatitis A virus (HAV), that shows a strong cytopathic effect on the Frp/3 cell line 7-9 days post-infection. Treatment of Frp/3 at a dose range of 125-1200 micrograms/ml had no toxic effect and showed a dose dependent inhibition of the HAV replication cycle. At the methisoprinol dose of 500 micrograms/ml the cytopathic effect was completely abolished and HAV antigen production reduced by 50% as measured by indirect immunofluorescence (IIF) and commercial enzyme-linked assay (ELISA). The virus yield was virtually abolished at the highest dose employed (1000 micrograms/ml).

Enhancement of hepatitis A propagation in tissue culture with 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole.

The adenosine analog 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) was found to increase the production of hepatitis A (HAV) antigen in two monkey kidney cell lines (Frhk-4 and Vero cells). DRB, a known inhibitor of the synthesis of messenger RNA, caused moderate changes in cell morphology. However, Frhk-4 cells could be maintained for several weeks at 80 microM of DRB, the concentration that caused maximal enhancement on HAV. DRB should be present from about the time of virus inoculation and its strongest effect was seen at low multiplicities of infection. Using radioimmunofocus assay it could be shown that DRB increased the amount of infectious virus. DRB treatment was applied in primary isolation of HAV from feces. In nine of ten strains HAV antigen expression was strongly increased and in six of the ten strains infectivity of harvested material increased by one 10log or more. DRB thus seems to be a useful enhancer of HAV growth in tissue culture.