J. B. Hudson

HYPOCRELLIN, FROM HYPOCRELLA BAMBUASE, IS PHOTOTOXIC TO HUMAN-IMMUNODEFICIENCY-VIRUS

Abstract Hypocrellin, a photodynamic perylene quinonoid isolated from the Chinese medicinal fungus Hypocrella bambuase, was evaluated for antiviral activity against the human immunodeficiency virus (HIV‐1). Hypocrellin was phototoxic to HIV‐1, almost as good as the structurally similar plant pigment hypericin, and like hypericin its activity required visible light. In contrast peroxyhypocrellin had little or no effect on the virus.

Antiviral activities of hypericin

Hypericin, a photodynamic plant quinone, readily inactivated murine cytomegalovirus (MCMV), Sindbis virus, and human immunodeficiency virus type 1 (HIV-1), especially on exposure to fluorescent light. Sindbis virus was significantly more sensitive than MCMV. The inactivated MCMV, when used to infect cells, was incapable of synthesizing early or late viral antigens. In addition to this direct virucidal effect, when hypericin was added to cells infected with viable MCMV, inhibition was also observed, particularly when the compound was added in the first two hours of infection. Again the antiviral effect was augmented by visible light. At effective antiviral concentrations, there were no discernible adverse effects on cultured cells. Thus hypericin appears to have two modes of antiviral activity: one directed at the virions, possibly on membrane components (although other virion targets cannot be ruled out), and the other directed at virus-infected cells. Both activities are substantially enhanced by light. Other recent studies on the antiviral activities of hypericin have not considered the role of light, and it is conceivable that apparent discrepancies between their results may have reflected different conditions of light exposure.

Antiviral and antimicrobial activities of Colombian medicinal plants

Strong antiviral and antimicrobial activities were detected in methanolic extracts of 24 plants used medicinally in the treatment of skin infections in four different regions of Colombia. Thirteen extracts displayed activity against herpes simplex virus (HSV) whereas none was active against poliovirus. The antiviral activity was indicated by a total inhibition of viral cytopathic effects (CPE) at a non-cytotoxic concentration of the extract. The most potent extract was obtained from Byrsonima verbascifolia (L.) HBK. which showed anti-HSV activity at a concentration as low as 2.5 microg/ml. Antimicrobial screening was conducted using the disc diffusion assay against Klebsiella pneumoniae, Escherichia coli, Streptococcus faecalis, Mycobacterium phlei, Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella typhimurium and the human pathogenic yeast, Candida albicans. Anti-Candida activity was observed for Piper lanceaefolium HBK. and Juglans neotropica Diels. Twenty-two extracts displayed activity against Gram-positive bacteria whereas none was active against the Gram-negative species. We concluded that these Colombian medicinal plants represent an untapped source of potentially useful antivirals and are worthy of further study.

Antiviral activities of Nepalese medicinal plants

In a screening of plants used traditionally in Nepal to treat diseases that could be caused by viruses, methanol extracts from 21 species were assayed for activity against three mammalian viruses: herpes simplex virus, Sindbis virus and poliovirus. Assays were performed in UV-A or visible light, as well as dark. Individual species of Hypericum, Lygodium, and Maesa exhibited impressive antiviral activities, although their selective effects on the three viruses suggested that the antiviral ingredients were different in each extract. In addition, many of the other extracts showed partial inactivation of one or more test viruses.

ANTIVIRAL ACTIVITY OF THE PHOTOACTIVE PLANT PIGMENT HYPERICIN

The polycyclic compound hypericin, a known photodynamic agent, was investigated for antiviral activity in the presence and absence of light. The three viruses tested: murine cytomegalovirus; Sindbis virus; and human immunodeficiency virus type 1, were all susceptible to hypericin; but these antiviral activities were considerably enhanced, in a dose‐dependent manner, by exposure to light.

Investigation of medicinal plants of Togo for antiviral and antimicrobial activities.

Methanol extracts were prepared from 19 medicinal plants of Togo and, by means of standard laboratory tests, were analysed for antiviral and antibiotic activities. Ten of the 19 showed significant antiviral activity and all but two displayed antibiotic activity. Extracts of three species, Adansonia digitata (the most potent), Conyza aegyptiaca and Palisota hirsuta , were active against all three test viruses (herpes simplex, Sindbis and poliovirus). The other seven, however, were more selective, showing activity against only one or two viruses. The antibiotic profiles varied considerably. The observation that each extract showed a distinctive permutation of target organisms suggests that different bioactive phytochemicals are present in each species. Only two of the extracts were devoid of bioactivity.

Antiviral Activities of Photoactive Perylenequinones

Nine perylenequinones (PQ), including some familiar naturally occurring pigments, were compared for their light‐mediated antiviral efficacies. Calphostin C was the most active compound against the two target viruses, herpes simplex virus type 1 and Sindbis virus. Hypo‐crellins A and B were also very active. However, three cercosporin‐like PQ were substantially less active in spite of their high quantum yields of singlet oxygen, whereas phleichrome, another efficient singlet oxygen producer, showed no detectable antiviral activity. One other PQ, which was a very weak singlet oxygen producer, also showed no antiviral activity. None of the active compounds showed significant antiviral activity in the dark. Thus, for some groups of PQ there was correlation between quantum yield of singlet oxygen C02) and antiviral efficacy, but there are evidently other structural features of PQ that influence activity.

Cytomegalovirus infectivity: Analysis of the phenomenon of centrifugal enhancement of infectivity

Abstract The phenomenon of centrifugal enhancement of infectivity was examined in some detial for the murine cytomegalovirus (MCV). Centrifugal enhancement (meaning that application of virus to monolayer cultures with the aid of a centrifugal field resulted in a 20- to 80-fold increase in infectious centers), was observed in mouse embryo cultures from three different strains of mice, in 3T3 cells, and in rat kidney cells. Three different strains of MCV and 20 plaque-purified strains of MCV all showed the property, as did the one strain of human cytomegalovirus examined. In contrast, herpes simplex virus type 1 and type 2 did not. Centrifugal enhancement could not be explained by increased penetration of MCV or its DNA into cells and their nuclei. Other experiments involving PFU-dose response, uv-inactivation kinetics, electron microscopy, and a variety of labeling regimes with thymidine and uridine isotopes, ruled out the presence of interfering microorganisms. It is concluded, therefore, that the property of centrifugal enhancement is an inherent property of MCV particles, and furthermore, it is suggested that some cytomegaloviruses may have a tendency to enter into a nonreplicating state in homologous fibroblasts.

Anti-viral properties and mode of action of standardized Echinacea purpurea extract against highly pathogenic avian Influenza virus (H5N1, H7N7) and swine-origin H1N1 (S-OIV).

BackgroundInfluenza virus (IV) infections are a major threat to human welfare and animal health worldwide. Anti-viral therapy includes vaccines and a few anti-viral drugs. However vaccines are not always available in time, as demonstrated by the emergence of the new 2009 H1N1-type pandemic strain of swine origin (S-OIV) in April 2009, and the acquisition of resistance to neuraminidase inhibitors such as Tamiflu® (oseltamivir) is a potential problem. Therefore the prospects for the control of IV by existing anti-viral drugs are limited. As an alternative approach to the common anti-virals we studied in more detail a commercial standardized extract of the widely used herb Echinacea purpurea (Echinaforce®, EF) in order to elucidate the nature of its anti-IV activity.ResultsHuman H1N1-type IV, highly pathogenic avian IV (HPAIV) of the H5- and H7-types, as well as swine origin IV (S-OIV, H1N1), were all inactivated in cell culture assays by the EF preparation at concentrations ranging from the recommended dose for oral consumption to several orders of magnitude lower. Detailed studies with the H5N1 HPAIV strain indicated that direct contact between EF and virus was required, prior to infection, in order to obtain maximum inhibition in virus replication. Hemagglutination assays showed that the extract inhibited the receptor binding activity of the virus, suggesting that the extract interferes with the viral entry into cells. In sequential passage studies under treatment in cell culture with the H5N1 virus no EF-resistant variants emerged, in contrast to Tamiflu®, which produced resistant viruses upon passaging. Furthermore, the Tamiflu®-resistant virus was just as susceptible to EF as the wild type virus.ConclusionAs a result of these investigations, we believe that this standard Echinacea preparation, used at the recommended dose for oral consumption, could be a useful, readily available and affordable addition to existing control options for IV replication and dissemination.

Ozone gas is an effective and practical antibacterial agent

BACKGROUND Bacterial infections continue to pose a threat to health in many institutional and communal settings, and epidemics are frequent. Current control measures are clearly inadequate; thus, there is a need for a simple, effective, and safe way to decontaminate surfaces. METHODS We evaluated the efficacy of a portable ozone-generating machine, equipped with a catalytic converter and an accessory humidifier, to inactivate 15 different species of medically important bacteria. RESULTS An ozone dosage of 25 ppm for 20 minutes, with a short burst of humidity in excess of 90% relative humidity, was able to inactivate more than 3 log(10) colony-forming units of most of the bacteria, including Acinetobacter baumannii, Clostridium difficile, and methicillin-resistant Staphylococcus aureus, in both in a laboratory test system and simulated field conditions. In many cases, complete eradication was achieved. Dried and wet samples were equally vulnerable to the ozone. Inactivation of bacterial samples dried onto soft surfaces (eg, fabric, cotton, filter paper) were comparable with that observed for samples on plastic. CONCLUSIONS The ozone generator can provide a valuable decontamination tool for the removal of bacteria in many institutional and communal settings, including hospitals and other health care institutions.