In vitro effects of bufotenine against RNA and DNA viruses.

Bufotenine, an alkaloid that can be found in plant extracts and skin secretions of amphibians, is reported to have potential antiviral activity. The present study evaluated the antiviral activity of bufotenine against different genetic lineages of rabies virus (RABV, a single-stranded, negative-sense RNA virus), canine coronavirus (CCoV, a positive-sense RNA virus) and two double-stranded DNA viruses (two strains of herpes simplex virus type 1/HSV-1 [KOS and the acyclovir-resistant HSV-1 strain 29R] and canine adenovirus 2, CAV-2). The maximal non-toxic bufotenine concentrations in Vero and BHK-21 cells were determined by MTT assays. The antiviral activity of bufotenine against each virus was assessed by examination of reductions in infectious virus titres and plaque assays. All experiments were performed with and without bufotenine, and the results were compared. Bufotenine demonstrated significant RABV inhibitory activity. No antiviral action was observed against CCoV, CAV-2 or HSV-1. These findings indicate that the antiviral activity of bufotenine is somewhat linked to the particular infectious dose used and the genetic lineage of the virus, although the mechanisms of its effects remain undetermined.

Cedratvirus getuliensis replication cycle: an in-depth morphological analysis.

The giant viruses are the largest and most complex viruses in the virosphere. In the last decade, new members have constantly been added to this group. Here, we provide an in-depth descriptive analysis of the replication cycle of Cedratvirus getuliensis, one of the largest viruses known to date. We tracked the virion entry, the early steps of virus factory and particles morphogenesis, and during this phase, we observed a complex and unique sequential organization of immature particle elements, including horseshoe and rectangular compartments, revealed by transverse and longitudinal sections, respectively, until the formation of the final ovoid-shaped striped virion. The genome and virion proteins are incorporated through a longitudinal opening in the immature virion, followed by the incorporation of the second cork and thickening of the capsid well. Moreover, many cell modifications occur during viral infection, including intense membrane trafficking important to viral morphogenesis and release, as evidenced by treatment using brefeldin A. Finally, we observed that Cedratvirus getuliensis particles are released after cellular lysis, although we obtained microscopic evidence that some particles are released by exocytosis. The present study provides new information on the unexplored steps in the life cycle of cedratviruses.

In vitro antiviral activity of plant extracts from Asteraceae medicinal plants.

BACKGROUND: Due to the high prevalence of viral infections having no specific treatment and the constant appearance of resistant viral strains, the development of novel antiviral agents is essential. The aim of this study was to evaluate the antiviral activity against bovine viral diarrhea virus, herpes simplex virus type 1 (HSV-1), poliovirus type 2 (PV-2) and vesicular stomatitis virus of organic (OE) and aqueous extracts (AE) from: Baccharis gaudichaudiana, B. spicata, Bidens subalternans, Pluchea sagittalis, Tagetes minuta and Tessaria absinthioides. A characterization of the antiviral activity of B. gaudichaudiana OE and AE and the bioassay-guided fractionation of the former and isolation of one active compound is also reported. METHODS: The antiviral activity of the OE and AE of the selected plants was evaluated by reduction of the viral cytopathic effect. Active extracts were then assessed by plaque reduction assays. The antiviral activity of the most active extracts was characterized by evaluating their effect on the pretreatment, the virucidal activity and the effect on the adsorption or post-adsorption period of the viral cycle. The bioassay-guided fractionation of B. gaudichaudiana OE was carried out by column chromatography followed by semipreparative high performance liquid chromatography fractionation of the most active fraction and isolation of an active compound. The antiviral activity of this compound was also evaluated by plaque assay. RESULTS: B. gaudichaudiana and B. spicata OE were active against PV-2 and VSV. T. absinthioides OE was only active against PV-2. The corresponding three AE were active against HSV-1. B. gaudichaudiana extracts (OE and AE) were the most selective ones with selectivity index (SI) values of 10.9 (PV-2) and > 117 (HSV-1). For this reason, both extracts of B. gaudichaudiana were selected to characterize their antiviral effects. Further bioassay-guided fractionation of B. gaudichaudiana OE led to an active fraction, FC (EC50 = 3.1 µg/ml; SI = 37.9), which showed antiviral activity during the first 4 h of the viral replication cycle of PV-2 and from which the flavonoid apigenin (EC50 = 12.2 ± 3.3 µM) was isolated as a major compound. CONCLUSIONS: The results showed that, among the species studied, B. gaudichaudiana seemed to be the most promising species as a source of antiviral agents.

Acridones as antiviral agents: synthesis, chemical and biological properties.

Acridones are a class of compounds that have attracted attention in recent years for their wide range of biological properties, including selective inhibition of diverse human pathogenic viruses. The wide spectrum of antiviral activity includes DNA and RNA viruses, such as herpes simplex virus, cytomegalovirus, adenovirus, hepatitis C virus, dengue virus, and Junin virus, among others, indicative of the involvement of cellular factors as potential targets of acridone derivatives. At the present, their precise mode of action is not clearly determined, although the predominant action seems to be centered on the synthesis of nucleic acids. Regarding this point, inhibitory activity against cellular and viral enzymes and the ability to intercalate into nucleic acid molecules was demonstrated for some acridone compounds. Then, the possibility of a multiple effect on different targets renewed interest in these agents for virus chemotherapy allowing a potent inhibitory effectiveness associated to less feasibility of generating antiviral resistance. This review summarizes the current knowledge regarding the methods of synthesis, the antiviral properties of acridone derivatives, their mechanism of action, and structural characteristics related to antiviral activity as well as the perspectives of this class of compounds for clinical application against human viral infections.

Antiviral sulfated steroids from the ophiuroid Ophioplocus januarii.

One new and three known sulfated steroidal polyols have been isolated from the ophiuroid Ophioplocus januarii, collected at San Antonio Oeste, Río Negro, Argentina. The four compounds possess 4 alpha,11 beta-dihydroxy-3 alpha,21-disulfoxy substituents and the A/B cis ring junction but differ in the side chain. The new compound has been characterized as (22E)-5 beta-24-norcholest-22-ene-3 alpha,4 alpha,11 beta,21-tetrol 3,21-disulfate (4). The structures of the four compounds were determined from spectral data and comparison with those of related steroidal polyols. The four compounds were tested for their inhibitory effect on the replication of one DNA and three RNA viruses. Compounds 2 and 4 were active against respiratory syncytial and polio viruses, and compound 3 inhibited Junin virus, responsible for Argentine hemorrhagic fever.