Comparison of the effects of chlorite-oxidized oxyamylose and polyacrylic acid on the multiplication of phytopathogenic viruses

Polyacrylic acid (PAA) and chlorite-oxidized oxyamylose (COAM) inhibit the multiplication of tobacco mosaic virus (TMV) in leaf disks by up to 50%. The reduction in TMV content is time-dependent and decreases with longer time intervals between the virus infection and the application of substances. The multiplication of potato virus X (PVX) in leaf disks is not affected by either PAA or COAM. In intact plants PAA produces a strong antiviral effect on both PVX and red clover mottle virus (RCMV). The effect produced by COAM is much less pronounced, although this substance is less toxic and could be used in a higher concentration than PAA. Neither of these compounds has a significant influence on the development of virus-induced necroses in Nicotiana glutinosa, Gomphrena globosa or Phaseolus vulgaris plants when administered one day before or after virus infection.     

Synthesis of newer N-furylidene and N-acetophenonylidene-5-chlorodiphenylamine-2-carboxylic acid hydrazides as antiviral and antibacterial agents

Five N-furylidene and fifteen N-acetophenonylidene-5-chlorodiphenylamine-2-carboxylic acid hydrazides were synthesized by the condensation of 5-chlorodiphenylamine-2-carboxylic acid hydrazides with furfuraldehyde and appropriate acetophenones. All the N-acetophenonylidenes thus synthesized were screened for their antiviral activity against animal viruses (Ranikhet disease virus and vaccinia virus in a stationary culture of chorioallantoic membrane of chick embryo) and against plant virus, namely gomphrena mosaic virus (GMV) in vitro as well as in vivo. Whereas five N-furylidenes were tested against gomphrena mosaic virus only in vitro and in vivo for their antiviral activity. Maximum significant protection was observed to the extent of 20% against Ranikhet disease virus. The majority of these compounds showed highly significant antiviral activity up to the extent of 96% in vitro and 89% in vivo against gomphrena mosaic virus. These compounds were also screened for their antibacterial activity against two micro-organisms; Bacillus subtilis and Staphylococcus aureus. Almost all of them were found to exhibit significant inhibition against B. subtilis while only a fewer showed significant inhibition against S. aureus.     

Design,Synthesis, Anti‐Tobacco Mosaic Virus (TMV) Activity,and SARs of 7‐Methoxycryptopleurine Derivatives

A series of 7‐methoxycryptopleurine derivatives 2 – 23 were prepared and evaluated for their antiviral activity against tobacco mosaic virus (TMV) for the first time. The bioassay results showed that most of these compounds exhibited excellent in vivo anti‐TMV activity, of which 7‐methoxycryptopleurine salt derivatives 16 , 19, and 23 displayed significantly higher activity than 7‐methoxycryptopleurine ( 1 ) and commercial ribavirin and ningnanmycin. Salification, the most commonly employed method for modifying physical‐chemical properties, did significantly increase antiviral activity, and different salt forms displayed different antiviral effect. This study provides fundamental support for development and optimization of phenanthroquinolizidine alkaloids as potential inhibitors of plant virus.     

Synthesis of some new substituted thiosemicarbazides as potential antiviral agents

The substituted thiosemicarbazides 1–15 , synthesized by the condensation of substituted 5-chloro-diphenylamine-2-carboxylic acid hydrazides with appropriate arylisothiocyanates, have been tested for their antiviral activity against the plant virus, sunnhemp rosette virus, in vitro as well as in vivo and against the animal virus, ranikhet disease virus, in a stationary culture of chorioallantoic membranes of chick embryo. The majority of these compounds showed significant antiviral activity against both viruses. The structure-activity relationships have further been studied and are discussed.     

In vitro anti-influenza activity of a protein-enriched fraction from larvae of the housefly (Musca domestica)

Context: Insects are a large, unexplored and unexploited source of potentially useful compounds for modern medicine. The larvae of the housefly (Musca domestica) have been used to study immune-induced molecules because they can survive in pathogenic environments.

Objective: The antiviral activity of a protein-enriched fraction (PEF) from the larvae of the housefly was evaluated in vitro and the possible antiviral mechanism was studied.

Materials and methods: PEF was isolated from the larvae of the housefly. The cytotoxicity of PEF was detected by the MTT assay. The in vitro antiviral activity of PEF against influenza virus was investigated. PEF was incubated with the virus and its target cells under various conditions, and its antiviral effects were examined by reduction in virus yield in cell cultures. Experiments with ribavirin were performed in parallel under the same conditions.

Results: The results indicated that PEF had minimal cytotoxicity against MDCK cells and the CC₅₀ value was calculated to be 284.45 μg/ml. The antiviral results showed the loss of infectious capacity was more than two log (2) units in cell cultures compared with virus control. The effect of PEF was direct virucidal activity and the interference on the adsorption of cell and virus. The antiviral mechanism of PEF is different from ribavirin.

Conclusion: The results indicate that PEF showed strong antiviral activity against influenza virus at a very early stage of the interaction with virus particles or their entry into the cells. PEF has a great potential as a resource of healthy products.     

Synthesis and Biological Evaluation of Strictosamide Derivatives with Improved Antiviral and Antiproliferative Activities

A series of novel derivatives of strictosamide were synthesized and biologically evaluated. Most of the new compounds exhibited improved activities than the parent compound strictosamide. Among them, compounds Ib and If possessed antiviral activities against influenza A virus (A/Jinan/15/90) with IC₅₀ values of 4.12 and 12.35 μg/mL, respectively. Compound Ie possessed antiviral activity against respiratory syncytial virus (RSV) with an IC₅₀ value of 9.58 μg/mL. Both compounds IIc and IId had moderate antiproliferative effects against five human cancer cell lines. The preliminary structure‐activity relationships were also concluded. This study provides a promising new template with potential antiviral activity.     

Recent patents on antibacterial, antifungal and antiviral properties of tea

Teas have beneficial effects on human health including cardioprotective, anticarcinogenic, antibacterial, antiviral and antifungal activity. The precise antimicrobial spectrum of tea is difficult to be defined due to variation in the methods of testing that have been used. Antibacterial effects of tea have been demonstrated against a number of microorganisms including Staphylococcus aureus, Vibrio cholerae, Escherichia coli, Shigella spp., Salmonella spp., Bacillus spp., Klebsiella spp. and Pseudomonas aeruginosa. Teas and tea ingredients seem to have both bactericidal and bacteriostatic actions. In addition, tea catechins have been shown to modify the antibiotic sensitivity of bacteria and to alter the expression of factors that determine bacterial virulence. Antiviral effects of green tea have been demonstrated against the influenza virus, as well as against the Herpes simplex virus, tobacco mosaic virus, enterovirus, rotavirus, Epstein Barr virus, HIV virus. Yet, green tea catechins have been shown to have antiviral activities against HIV infection. Antifungal effects of tea have been reported against Candida albicans, Trichophyton mentagrophytes, and Trichophyton rubrum. The present paper describes recent patents on antimicrobial effect of teas and tea ingredients.     

Synthesis and antiviral activity of quinoxalinedione 2,3(1H, 4H) derivatives

Syntheses and Antiviral Activities of Quinoxalinedione 2,3(1H,4H) Derivatives In our search for new virustatics, we have synthesized derivatives of quinoxaline-2,3(1H,4H)-dione and investigated their antiviral activities against various strains of herpes simplex virus types 1 and 2, vaccinia virus and vesicular stomatitis virus. None of the compounds showed antiviral activity comparable to that of 5-ethyl-2′-deoxyuridine (EtUdR).     

Synthesis and anti-hepatitis B activity of new substituted uracil and thiouracil glycosides

A number of N- and S-substituted uracil and thiouracil glycosides were synthesized by coupling reaction of 5,6-dibenzyle pyrimidine derivatives with the corresponding acetobromosugar. The synthesized compounds were tested for their antiviral activity against hepatitis B virus. Plaque reduction infectivity assay was used to determine virus count reduction as a result of treatment with tested compounds which showed moderate to high antiviral activities.     

Characterization of Antiviral Activities in Echinacea. Root Preparations

Abstract

The roots of three commonly used taxa of Echinacea.—E. purpurea., E. pallida. var. pallida., and E. pallida. var. angustifolia.—were extracted and fractionated by means of accelerated solvent extraction to reflect the most commonly used methods for commercial preparations. These fractions were analyzed by HPLC for their content of caffeic acid derivatives and alkamides and for antiviral activities against three viruses often implicated in colds and influenza. Aqueous extracts of E. purpurea. root contained a relatively potent activity against herpes simplex virus (HSV) and influenza virus (FV) but not against rhinovirus (RV). These fractions had low amounts of caffeic acids and alkamides. The ethyl acetate fraction contained significant but weak activity against both HSV and FV and contained significant levels of cichoric acid. In contrast, E. pallida. var. angustifolia. gave no water-soluble antiviral activity, but the ethanolic and ethyl acetate fractions contained significant activity against all three viruses, and this activity correlated with the presence of alkamides. E. pallida. var. pallida., however, gave no antiviral activity in any of the fractions, and this observation accorded well with the near absence of the marker compounds. Thus, we have detected a relatively potent water-soluble antiviral activity in E. purpurea. root, together with the weaker antiviral cichoric acid; an antiviral alkamide fraction in E. pallida. var. angustifolia.; but no antiviral activity in E. pallida. var. pallida.. Therefore, different types of Echinacea. root preparations, such as tinctures, tablets, and teas, based on different species and extraction methods, would be expected to offer quite different antiviral profiles.     

Patent Evaluation Anti-infectives: Phosphonic acid prodrugs with improved antiviral activity

This patent discloses lipid derivatives as prodrugs for antiviral agents. It relates particularly to lipid prodrugs of phosphonic acids and their use in the treatment of viral infections. The invention claims a series of improved prodrugs of phosphonoformate (PFA), phosphonoacetate (PAA) and their analogues, with increased in vitro antiviral activity over the parent compounds against human cytomegalovirus (HCMV), herpes simplex virus (HSV) and human immunodeficiency virus (HIV).     

Antiviral agents, XII1): 2-Amino-4-arylamino-s-triazines substituted on the nucleus (author's transl)]

Antiviral Agents, XII : 2-Amino-4-arylamino-s-triazines Substituted on the Nucleus The aminomethinylation reaction effected by s-triazine ( 4 ) may also be applied to 1-arylbiguanides carrying methylthio-, methoxy-, and ethoxy-carbonyl groups on the nucleus. Of the 2-amino-4-arylamino-s-triazines 7 so prepared, antiviral activity is exhibited by 7a–c against Herpes simplex virus and by 7d–f against Newcastle disease virus.     

Inhibition activities of polysaccharide (RG4-1) from Gentiana rigescens against RSV

Respiratory syncytial virus (RSV) is the most important cause of lower respiratory tract infection in infants and young children. With the emergence of drug-resistant strains of RSV, new antiviral agents are needed urgently. Gentiana rigescens is a kind of Chinese herb, belonging to Gentianaceae, which has long been used as a folk medicine for curing inflammation, bacterial infection, viral infection, and so on. In this research, polysaccharide designated RG4-1 was isolated from G. rigescens by hot water extraction, ethanol precipitation, and macroreticular adsorbing resin column chromatography, and its antiviral activity, cytotoxicity, and possible antiviral mechanisms were assayed by cytopathogenic effect inhibition assay, 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, and plaque reduction assay. RG4-1 was a fructose-binding lectin. In host cell cultures, RG4-1 was found to be an effective antiviral component against RSV. It showed good inhibitory effect against RSV when it was added 2 h after virus infection with 50% effective concentration of 12.86 μg/ml. RG4-1 also displayed its direct inactivation, attachment inhibition effect, and penetration inhibition effect against RSV. A time-dependent experiment was set up to confirm that RG4-1 blocked RSV infection at early stages of the infection. But RG4-1 seemed to be ineffective against intracellular virus and viral biosynthesis.     

抗病毒药物的研究 Ⅱ.乙酰苯衍生物的合成

本文报导了某些取代苯与脂肪族的溴代甲基酮(I_a-j),单取代苯α-酮醛(II_a-c)及其与对氨基苯甲酸的缩合物(III_a-c)等的合成。抗病毒筛选结果,除化合物I_j外,其余化合物在鸡胚绒毛尿囊膜组织培养中,对流感病毒均有抑制作用。     

Inhibition of viral RNA synthesis in canine distemper virus infection by proanthocyanidin A2

Canine distemper virus (CDV) is a contagious and multisystemic viral disease that affects domestic and wild canines as well as other terrestrial and aquatic carnivores. The disease in dogs is often fatal and no specific antiviral therapy is currently available.In this study, we evaluated the in vitro antiviral activity against CDV of proanthocyanidin A2 (PA2), a phenolic dimer belonging to the class of condensed tannins present in plants. Our results showed that PA2 exerted in vitro antiviral activity against CDV with a higher selectivity index compared to ribavirin, included in our study for the previously tested anti-CDV activity. The time of addition assay led us to observe that PA2 was able to decrease the viral RNA synthesis and to reduce progeny virus liberation, at different times post infection suggesting multiple mechanisms of action including inhibition of viral replicative complex and modulation of the redox milieu. These data suggest that PA2, isolated from the bark of Aesculus hippocastanum, has potential usefulness as an anti-CDV compound inhibiting viral replication.     

Potential Biologically Active Agents,XXXII. Synthesis and Antiviral Activity of Some 3-(Arylthiosemicarbazono)-2-indolinones

A series of 3-(arylthiosemicarbazono)-2-indolinones 1 , 1-methyl-3-(arylthiosemicarbazono)-2-indolinones 2 and 1-(aminomethyl)-3-(arylthiosemicarbazono)-2-indolinones 3 have been synthesised. All compounds were screened for their antiviral activity against Sunnhemp rosette virus (SRV) in vitro as well as in vivo. Twelve compounds show significant antiviral activity.     

Quantitative Structure–Activity Relationships (QSARs) of Pyrimidine Nucleosides as HIV-1 Antiviral Agents

The structural requirements for the antiviral activity of pyrimidine nucleosides against HIV-1 virus was evaluated with the Hansch SAR analysis. Antiviral activity is best related to the hydrophobicity and steric (L and B3) properties of the substituent at the C5 of pyrimidine ring. Further, the antiviral activity is related to B4 of the substituent at position 3' of the sugar ring with a positive slope. The activity of both uracil and cytosine derivatives can be related to their structure by the same equations, which indicates that the SARs are similar in these two groups of congeners. These results suggest that compounds with a small substituent at the 5 position of the pyrimidine ring and a flat substituent at the 3' position of the sugar ring will be the most active compounds against HIV-1 virus.     

Protective effect of partially purified 35 kDa protein from silk worm (Bombyx mori) fecal matter against carbon tetrachloride induced hepatotoxicity and in vitro anti-viral properties

Context: It has been found that many proteins from silkworm (Bombyx mori L.) fecal matter have been active against human immunodeficiency virus, Sendai virus, herpes simplex virus type-1, and nuclear polyhedrosis virus.

Objective: A partially purified 35?kDa protein from silkworm was screened for its hepatoprotective activity, and in vitro antioxidant, and antiviral properties against camelpox and goatpox viruses.

Materials and methods: The study investigated the efficiency of the partially purified 35kDa protein from silk worm fecal matter against CCl₄-induced liver damage measured in terms of enzyme levels such as aspartate aminotransferase (AST), alanine amino transferase(ALT), alkaline phosphatase (ALP) and total bilirubin, which maintain liver integrity. In vitro antioxidant potential of this protein was determined based on its ability to scavenge 2, 2-diphenylpicrylhydrazyl (DPPH) and superoxide anions scavenging activity. Further, in vitro cytotoxic effect on Vero cells and antiviral activity against goatpox and camelpox viruses were also studied.

Results: The protein had significant hepatoprotection against CCl₄-induced liver damage and scavenging of DPPH radical and superoxide anion activity. However, the protein did not inhibit the multiplication of either virus tested at its maximum non-toxic concentration (MNTC) in vitro.

Discussion and conclusion: The partially purified 35?kDa protein from silk worm Bombyx mori L fecal matter possessed protective effect against CCl₄-induced oxidative stress in rat model. The protein was found to be ineffective against camelpox and goatpox viruses at its MNTC in vitro.     

New in vitro method for evaluating antiviral activity of acyclic nucleoside phosphonates against plant viruses

A new method was developed for testing antiviral compounds against plant viruses based on rapidly growing brassicas in vitro on liquid medium. This method enables exchange of media containing tested chemicals in various concentrations and simultaneous evaluation of their phytotoxicity and antiviral activity. While using ribavirin as a standard for comparison, phytotoxicity and ability of the acyclic nucleotide analogues (R)-PMPA, PMEA, PMEDAP, and (S)-HPMPC to eliminate ssRNA Turnip yellow mosaic virus (TYMV) were evaluated by this method. Double antibody sandwich ELISA and real-time PCR were used for relative quantification of viral protein and nucleic acid in plants. Ribavirin had the most powerful antiviral effect against TYMV. On the other hand, (R)-PMPA and PMEA had no antiviral effect and almost no phytotoxicity compared to the control. (S)-HPMPC and PMEDAP showed moderate antiviral effect, accompanied by higher phytotoxicity. The tested compounds can be screened within 6-9 weeks in contrast to the 6 months for traditionally used explants on solid medium. The method enables large-scale screening of potential antivirals for in vitro elimination of viruses from vegetatively propagated crops and ornamentals.     

Design, synthesis and preliminary antiviral screening of new N-phenylpyrazole and dihydroisoxazole derivatives

A new series of N-phenylpyrazoles and dihydroisoxazles was synthesized starting from α,β-unsaturated ketones in basic media using phenyl hydrazine and hydroxylamine HCl, respectively. Antiviral evaluation of the target compounds revealed that the dihydroisoxazole derivatives have promising antiviral activity against hepatitis A virus and herpes simplex virus type 1.