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Screening of higher plants for biological activities. II. Antiviral activity.

Extracts prepared from 100 samples of higher plants were evaluated for antiviral activity against several viruses, including Semliki forest, coxsackie, measles, poliomyelitis, herpes, and adeno viruses. The plants were chosen from 73 genera and 43 families on the basis of literature data and medicinal reports on antimicrobial activity. The results of the antiviral testing showed that eight of these extracts exhibited a pronounced activity against one or more of the test viruses. Another three plant extracts showed a moderate level of antiviral activity against some of the test viruses.

Antiviral Agents↗
PubMed1975

Streptovirudins -- new antibiotics with antiviral activity. The antiviral spectrum and inhibition of Newcastle disease virus in cell cultures.

Streptovirudins are new antibiotics isolated as a mixture of several structurally related compounds from fermentations of Streptomyces griseoflavus (Krainsky) Waksman et Henrici var. thuringensis JA 10124. They possess antiviral activity against RNA and DNA viruses cultivated in chick embryo cells, namely Sindbis, fowl plague, Newcastle disease (NDV), pseudorabies, vaccinia and sheep abortion viruses. The naturally formed streptovirudin complex, in concentrations of 20-2.5 mug/ml inhibited the viral cytopathic effect and caused 100 percent plaque reduction. Mengo, Coxsackie B1-B5, ECHO 30 and 33, and polio (wild and attenuated types 1, 2, and 3) viruses grown in FL cells were not sensitive in the agar-diffusion plaque-inhibition test. The antibiotics failed to show a direct virucidal effect on the NDV virion itself or to influence virus adsorption and penetration processes. Addition of streptovirudin complex during a one-step growth cycle of NDV from 0-4 hours after virus adsorption resulted in complete suppression of virus yield. The antibiotic complex consists of two main groups: I - A1, B1, C1, D1, E1 and II - A2, B2, C2, D2, E2, each of which possess antiviral activity.

Anti-Bacterial Agents↗
PubMed1978

[Substances having antiviral activity. IX. Synthesis and antiviral activity of 1-acyl-2-halo-3-formylindole thiosemicarbazones].

Some thiosemicarbazones of 1-acyl-2-chloro-3-formylindoles were synthesized and investigated for antiviral activity against vaccinia virus, HID stock and parainfluenza virus type 3 HA-I/CR-8 stock. Evidence of antiviral activity was found only against vaccinia virus, and was particular significant with the m-substituted 1-benzoyl-2-chloro-3-formylindoles. The first results of 2-substitution of chlorine by bromine in the indole skeleton, are reported.

Antiviral Agents↗
PubMed1977

Simultaneous presence of antiviral activity and its degrader in Bacillus extracts.

Extracts of uninfected Bacillus species ATCC 27877 cells contained both an antiviral activity and a degrader for this activity. The antiviral activity was stable to 90 degrees C, caused a rapid inhibition of phage adsorption, and resulted in a gradual loss of phage infectivity. When extracts were incubated at 37 degrees C, the degrader inactivated the antiviral activity and the degrader was retained. When the extracts were heated at 90 degrees C, the degrader was inactivated and the antiviral activity was retained. A comparison was made of these two activities in extracts from cells of various incubation ages. The apparent association of maximal antiviral activity with prespore cells seemed due to the high content of degrader in vegetative and stationary cells. Both antiviral activity and its degrader appeared to be characteristics of vegetative cells.

Antiviral Agents↗
PubMed1975

Double-stranded complex of polyguanylic and polycytidylic acids and its antiviral activity in tissue culture.

The antiviral activity and conditions of formation of the most active double-stranded complexes of synthetic homopolynucleotides, polyriboguanylic and polyribocytidylic acids, were studied on the model of primary trypsinized chick embryo cells and RNA-containing viruses. The (poly G).(poly C) complex was very active against the viruses tested; their replication in cell cultures was inhibited completely. The antiviral activity of the (poly G).(poly C) complex increased markedly in the presence of diethylaminoethyl- (DEAE-) dextran. After treatment with 1 mug/ml of (poly G). (poly C) for 1 hour in the presence of 100 mug/ml DEAE-dextran, the cell sheet remained protected for 5-7 days. Preparations of (poly G).(poly C) obtained under optimal conditions were as active as (poly I).(poly C) complexes and exceeded them markedly in the level of the therapeutic index which under the present experimental conditions was 5-10 times 10(3) for (poly G).(poly C). Highly purified homopolymers with sufficiently high molecular weight must be used for production of active and stable (poly G).(poly C) complexes.

Animals↗
PubMed1976

Use of thyrotropin and cholera toxin to probe the mechanism by which interferon initiates its antiviral activity.

Thyrotropin (10 muM) inhibited the antiviral activity of interferon. When added after interferon, thyrotropin (TSH) had no effect on antiviral activity. There was also no inhibition of interferon action in cells washed with medium between incubations with TSH and interferon. 125I-Labeled TSH and 125I-labeled cholera toxin could bind to preparations of mouse L-cell plasma membranes. The binding was specific in that it was prevented by unlabeled thyrotropin or cholera toxin, but not by insulin, glucagon, prolactin, growth hormone, human chorionic gonadotropin, or luteinizing hormone. Mouse interferon inhibited 125I-labeled TSH binding to L-cell plasma membranes. The effect of mouse interferon on 125I-labeled cholera toxon binding was more complex, inhibition occurring only after an initial enhancement at low interferon concentrations. A 10-fold higher concentration of interferon was required to inhibit 125I-labeled TSH binding. Mouse interferon was also able to displace bound 125I-labeled TSH, but not bound 125I-labeled cholera toxin. The interferon interaction with cell membranes was temperature-sensitive. Human interferon could induce changes in binding of 125I-labeled TSH and 125I-labeled cholera toxin to mouse L-cell plasma membranes similar to those induced by mouse interferon. Mouse interferon induced similar changes in plasma membranes of human KB-3 cells, which are insensitive to both human and mouse interferons. In view of these results, the species specificity of interferons does not appear to reside solely at the point of the initial interaction with their binding sites.

Bacterial Toxins↗
PubMed1979

Enhancement of the antiviral activity of pyrimidine derivatives against mengovirus by visible light.

Eleven pyrimido-pyrimidine derivatives, seven with significant antiviral activity against Mengovirus, five against Coxsackie B1 virus and four antiviral negative compounds were tested for their photosensitizing ability. All seven compounds with antiviral activity in vitro showed an enhanced antiviral action against Mengovirus under irradiation with visible light, a fact that may be caused by photodynamic processes. It was tried to correlate the oxidation potentials of sensitizers with their photodynamic activity. By means of mass-spectrometric investigations, molecular fragmentation was examined following thin layer chromatography (TCL) before and after irradiation. Furthermore, binding affinity to biopolymers (BSA and RNA) was investigated to reveal conformity in differences of antiviral activity. The main results are the following: 1. Generally, strong antiviral activity can be correlated with strong binding affinity. 2. No significant correlation could be detected between oxidation potentials of antiviral compounds and their enhanced antiviral activity under irradiation conditions, although in some cases sensitizer with higher oxidation potentials are more effective than those with lower ones. 3. The lower the photostability of the compounds the higher was the light-induced antiviral activity. 4. No alteration of the molecular ion peak and fragmentation pattern before and after irradiation was indicated by means of mass-spectrometry and TLC using fairly comparable conditions.

Amnion↗
PubMed1979

Antiviral activity of aliphatic nucleoside analogues: structure-function relationship.

Of a series of 58 aliphatic nucleoside analogues, (S)-9-(2,3-dihydroxypropyl)adenine [(S)-DHPA] proved to be the most active congener, when assayed for antiviral activity in primary rabbit kidney cell cultures challenged with either vaccinia or vesicular stomatitis virus. Whereas most analogues derived from substituted purine and pyrimidine bases and bearing various hydroxy- or amino-substituted alkyl chains did not show evidence of antiviral activity at a concentration of 2 mM, (S)-DHPA inhibited both vaccinia and vesicular stomatitis virus replication at 0.05-0.1 mM. For 9-[(RS)-2,3-diazidopropyl]adenine and some di- and trihydroxybutyl analogues of DHPA, viz., 9-[(2RS,3SR)-2,3-dihydroxybutylladenine, 9-[(RS)- or 9-[(S)-3,4-dihydroxybutyl]adenine, 9-[(2S,3R)-2,3,4-trihydroxybutyl]adenine, and 3-(adenin-9-yl)-(RS)-alanine, an antiviral effect was noted at a concentration of 0.5-1 mM.

Adenine↗
PubMed1977

[Antiviral activity in the serum of patients with acute myelocytic leukemia: prognostic significance. Preliminary report].

In view of suggestions that acute myeloblastic leukemia (AML) may be of viral etiology, sera of 31 patients suffering from AML were investigated for antiviral activity. Fowl plague virus (FPV), vesicular stomatitis virus (VSV), BT 20 mammary carcinoma cells and chicken embryo fibroblasts (CEF) were used as assay systems. In the FPV-BT20 system, 19 of 20 patients whose blood sample was taken when they were in complete remission showed antiviral activity in their sera. These patients stayed in complete remission for at least three months after the blood sample was taken. In the sera of 11 patients no antiviral activity could be found with the FPV-BT20 assay system. 3 of the 11 were in relapse, 5 had a relapse within 3 months and 3 stayed in remission more than 3 months after the blood sample was taken. In the FPV-CEF and in the VSV-BT20 system antiviral activity was also found. The activity in the FPV-CEF system corresponded well with the FPV-BT20 assay and the disease status, whereas the activity detected by the VSV-BT20 system did not. The nature of the antiviral activities in the sera of AML patients against FPV and VSV is not yet clear. Interferon and specific antiviral antibodies can probably be ruled out. The antiviral activity against FPV appears to be a biological index of the activity of the disease and might eventually be used to determine intensity and length of treatment.

Animals↗
PubMed1978

Use of Semliki forest virus to identify lipid-mediated antiviral activity and anti-alphavirus immunoglobulin A in human milk.

In a simple and reliable assay system, Semliki forest virus (SFV) was used to detect the activity of antiviral factors in human milk. Fractionation of the milk showed that a heat-stable, lipid-associated activity and an immunoglobulin-associated activity were present, either singly or together, in 85% of the human milk samples tested. Cow and synthetic milk showed neither activity. Extraction of the neutral milk lipids allowed the antiviral to be located with the monoglyceride and free fatty acid fractions. The milk low in antiviral lipids and high in triglycerides also lacked a strong lipase activity. The immunoglobulin anti-SFV activity was shown to be due to immunoglobulin A, the major milk immunoglobulin, and appears to be directed against an alphavirus closely related to SFV, possibly Ross River virus.

Antibodies, Viral↗
PubMed1978

Deoxyadenosine antagonism of the antiviral activity of 9-beta-D-arabinofuranosyladenine and 9-beta-D-arabinofuranosylhypoxanthine.

Deoxyadenosine but not adenosine reversed the antiviral activity of 9-beta-D-arabinofuranosyladenine (ara-A) and 9-beta-D-arabinofuranosylhypoxanthine (ara-H) when used in the presence of coformycin, an inhibitor of adenosine deaminase. In suspension cultures of KB cells, 10 muM ara-A inhibited the replication of herpes simplex virus type 1 by 80%. Concomitant addition of 50 muM deoxyadenosine reduced the antiviral activity of 10 muM ara-A to only 40% inhibition. Adenosine failed to antagonize the antiviral activity. In monolayer cultures of KB cells, the 50% inhibitory concentration of ara-A was increased from 1.5 to 2.9 muM by 2 muM deoxyadenosine and to 8.5 muM by 10 muM deoxyadenosine. Analysis of the dose-response data by a double reciprocal plot method indicated that the antagonism was competitive. The antiviral activity of ara-H also was antagonized by deoxyadenosine. The 50% inhibitory concentration of ara-H was increased from 42 muM to 70, 91, or 121 muM by the concurrent addition of 5, 10, or 20 muM deoxyadenosine. Competitive antagonism could not be demonstrated. In the absence of the adenosine deaminase inhibitor, neither ara-A nor ara-H was antagonized by deoxyadenosine. Since such inhibitors were not available unitl recently, previous investigators were unable to observe the antagonistic capacity of deoxyadenosine.

Adenosine↗
PubMed1978

The influence of some thiosemicarbazone derivatives with antiviral activity on immune response in mice.

The aim of the present study was to examine the influence of the thiosemicarbazone-group of compounds with antiviral activity on the humoral and cellular immune response in R III, CBA and Balb/c mice, immunized with sheep erythrocytes or sensitized with oxazolon. The plaque forming cells test, according to Jerne's method and the oxazolon hypersensitivity test were performed. All of the examined compounds, inhibited the humoral immune response, and three of them decreased also the cellular response. The relationship between the antiviral activity and their immuno-suppressive activity has been discussed. Low antiviral activity of compound Hoe 105 could be due to its immunosuppressive action. Moreover, the mechanism of antiviral activity of one of the tested compounds, which displayed strong activity against vaccinia virus, was examined and compared with the activity of methisazone.

Animals↗
PubMed1975

Cyclic AMP potentiation of interferon antiviral activity and effect of interferon on cellular cyclic AMP levels.

Treatment of L cells with 3 to 10 mM 3':5'-cyclic adenosine monophosphate (cAMP) in the presence of interferon was found to potentiate the development of antiviral activity. The dose response of interferon activity at various time periods in the presence and absence of cAMP indicated that potentiation of interferon activity by cAMP occurred at an early stage in the development of antiviral activity. Among the analogues of cAMP tested for interferon-potentiating activity, only the acylated derivatives were found to be active. Combined L-epinephrine and theophylline treatment of cells elevated cellular cAMP levels and also potentiated interferon-mediated antiviral activity. Interferon was also found to elevate cAMP levels in L cells. This activity was limited to biologically active interferon and antagonized the depression of cAMP associated with vesicular stomatitis virus (VSV) infection of L cells. These observations suggest that some aspects of interferon's biological activity is associated with an alteration in cellular levels of cAMP.

Animals↗
PubMed1976

Antiviral activity in milk of possible clinical importance.

In human and in cow's milk an antiviral activity has been detected which does not seem to be related to antibodies or other known virus inhibitors. The antiviral activity lay in a relatively heat-stable macromolecule belonging to the non-fatty part of milk.

Animals↗
PubMed1979

Novel antiviral activity found in the media of Sindbis virus-persistently infected mosquito (Aedes albopictus) cell cultures.

Aedes albopictus (mosquito) cells persistently infected with Sindbis virus for a period of 6 months release into the medium a low-molecular-weight material capable of specifically reducing the yields of Sindbis virus during the "acute phase" of infection in mosquito cells. The antiviral activity was produced in detectable levels at 3 days after infection, and its concentration in the extracellular medium increased thereafter. The antiviral activity was inactivated by treatment with the enzyme protease K and heat. It was not activated by treatment with antibody prepared against extracts of Sindbis virus-infected BHK-21 cells. The antiviral activity differs from interferon produced by vertebrate cells in that it is virus specific as well as cell specific.

Aedes↗
PubMed1977

Antiviral activity of bovine interferons on primate cells.

Potent preparations of bovine leucocyte and fibroblast interferons had substantial antiviral activity on monkey cells and low activity on human cells. Thus, interferon from a 'lower' phylogenetic species can have considerable antiviral activity in primate cells, but not all primate cells are equally sensitive.

Animals↗
PubMed1976

Induction of antiviral activity in vivo and in vitro by human placenta ribonucleic acid treated with nitrous acid.

Induction of antiviral activity and interferon by human placenta ribonucleic acid deaminated with sodium nitrite (NO2-RNA) was studied in vitro and in vitro. (1) Viral multiplication in diploid cells from human kidney (HK cells) was depressed by pretreatment with NO2-RNA, but not by pre-treatment with the original placenta RNA. (2) NO2-RNA showed an interferon-inducing activity in rabbits and mice. (3) NO2-RNA sedimenting in 18 S and 28 S regions showed a higher antiviral activity than that sedimenting in 4 S region.

Adenine↗