Induction of cecropin-like and attacin-like antibacterial but not antiviral activity in Heliothis virescens larvae.

Inducible cecropin-like and attacin-like proteins were isolated from immune hemolymph obtained from vaccinated Heliothis virescens larvae. The attacin-like protein had a molecular weight of approximately 25,000 daltons and was not dialyzable. The cecropin-like peptide had an estimated molecular weight of 6,000-7,000 daltons and was dialyzable, heat-stable and sensitive to trypsin digestion.

Antiviral melanization reaction of Heliothis virescens hemolymph against DNA and RNA viruses in vitro.

1. Antiviral activity of Heliothis virescens larval hemolymph was determined using a cytotoxicity/virus inhibition test (TClD50) done in Vero cell tissue cultures. Excellent antiviral activity was found especially against herpes simplex viruses-1 and -2 and also against vesicular stomatitis, parainfluenza-3, coxsackie B3 and sindbis viruses.

Prevention of tilorone developmental toxicity with progesterone.

The immunomodulator tilorone hydrochloride was administered (gastric intubation) once to time-pregnant Upj:TUC(SD)spf (Sprague-Dawley) rats in four experiments. In experiment 1, tilorone (250 or 500 mg/kg) was administered on day 10 of gestation. The dams were killed 4 or 72 hr after dosing.

Unsaturated and carbocyclic nucleoside analogues: synthesis, antitumor, and antiviral activity.

A series of unsaturated analogues of nucleosides were prepared and their cytotoxic, antitumor, and antiviral activities were investigated. Alkylation of cytosine with (E)-1,4-dichloro-2-butene gave chloro derivative 2f, which was hydrolyzed to alcohol 2h. Cytosine, adenine, 2-amino-6-chloropurine, thymine, and (Z)-1,4-chloro-2-butene gave compounds 4c-f, which, after hydrolysis, afforded alcohols 4a, 4b, 4g, and 4h.

Bropirimine-induced embryolethality after oral administration to the pregnant rat.

Oral bropirimine (an immunomodulator shown to induce interferon) was administered to timed-pregnant Sprague-Dawley rats in five experiments utilizing several different dosing schedules. Concentrations of 100, 200, and 400 mg/kg of bropirimine were used. Interferon levels were determined in maternal serum, spleen, and whole embryo extracts and uterine contents were evaluated for survival of the embryos.

Peptides as potential virus inhibitors. Synthesis and bioassay of five respiratory syncytial virus peptide analogs with antimeasles activity.

Five carbobenzoxylated and D-amino acid containing-peptide analogs of the respiratory syncytial virus (RSV) F1 glycoprotein amino terminus were chemically synthesized by solution and FMOC-solid phase peptide synthesis methods. Several of these peptides, ranging from 3 to 6 residues in length, raised the bilayer to hexagonal phase transition temperature of dielaidoylphosphatidylethanolamine. None of these peptides were specific inhibitors of RSV or herpes simplex virus infection.

Bilayer stabilizing peptides and the inhibition of viral infection: antimeasles activity of carbobenzoxy-Ser-Leu-amide.

A number of carbobenzoxy-dipeptide-amides raise the bilayer to hexagonal phase transition temperature of dielaidoylphosphatidylethanolamine (stabilizes the bilayer). The potency of the peptides in stabilizing the bilayer phase is Z-Tyr-Leu-NH2 = Z-Gly-Phe-NH2 greater than Z-Ser-Leu-NH2 greater than Z-Gly-Leu-NH2 greater than Z-Gly-Gly-NH2. A linear correlation was found between the respective HPLC retention time parameter k' for the peptide and the slope of the bilayer stabilization curve determined with model membranes by differential scanning calorimetry.

Pyrimidinones. 1. 2-Amino-5-halo-6-aryl-4(3H)-pyrimidinones. Interferon-inducing antiviral agents.

Interferon induction and antiviral activity was discovered with 2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone. An analogue study incorporating a series of 2-amino-5-substituted-6-arylpyrimidinones revealed that the most potent interferon inducers were mono- and difluorophenyl analogues. These same analogues were also potent antiviral agents against Semliki Forest virus and herpes simplex type 1.

Antiviral and antitumor compounds from tunicates.

Tunicates provide a rich source of biologically active compounds with potentially useful medicinal properties. The most interesting compounds identified thus far are the didemnins, depsipeptides from a Caribbean Trididemnum species, which are potent inhibitors of L1210 leukemia cells in vitro and are also active in vivo against P388 leukemia and B16 melanoma. In addition the didemnins inhibit growth of a variety of RNA and DNA viruses in vitro and protect mice infected intravaginally with herpes simplex virus type 2.

Didemnins: antiviral and antitumor depsipeptides from a caribbean tunicate.

Extracts of samples of a Caribbean tunicate (ascidian, sea squirt) of the family Didemnidae inhibit in vitro at low concentrations the growth of DNA and RNA viruses as well as L1210 leukemic cells. The active compounds isolated from the tunicate, didemnins A, B, and C, are depsipeptides, and didemnin B (a derivative of didemnin A) is the component active at the lowest concentration in inhibiting viral replication in vitro and P388 leukemia in vivo.

Activities of 5,6-dihydro-5-azathymidine against herpes simplex virus infections in mice.

5,6-Dihydro-5-azathymidine (DHAdT), a nucleoside antibiotic inhibitory for herpes simplex virus (HSV) in cell cultures (H. E. Renis, Antimicrob.

beta-D-Arabinofuran[1',2':4,5]oxazolo-1,3,5-triazine-5-N-methyl-4,6-dione and analogues, unusually specific immunosuppressive agents.

Sequential treatment of the protected beta-D-arabinofuran[1',2':4,5]-2-aminooxazoline (2) with methyl isocyanate and diimidazole carbonyl afforded the 2,2'-anhydro-beta-D-arabinofuranosyl nucleoside, 6. Deprotection and hydrolysis yielded the corresponding arabinoside. Although the anhydronucleoside exhibited in vitro antiviral activity against herpes simplex type 1, it exacerbated the infection in vivo.

5,6-Dihydro-5-azathymidine: in vitro antiviral properties against human herpesviruses.

5,6-Dihydro-5-azathymidine (DHAdT), a novel water-soluble nucleoside antibiotic, inhibits herpes simplex virus type 1 (HSV-1) in appropriately infected cell cultures to a greater extent than herpes simplex virus type 2 (HSV-2). Vaccinia virus was less susceptible than HSV-2, and pseudorabies virus yields were not reduced at the concentrations studied. Plaque formation by varicella-zoster virus was suppressed by DHAdT.

Chemotherapy of genital herpes simplex virus type 2 infections of female hamsters.

The antiviral activity of 1-beta-d-arabinofuranosylcytosine (ara-C, cytarabine, Cytosar), 5-iodo-2'-deoxyuridine (IdUrd), 9-beta-d-arabinofuranosyladenine (ara-A), and disodium phosphonoacetate (PAA) have been compared in herpes simplex virus type 2 (HSV-2)-infected primary rabbit kidney cells and in female hamsters with genital HSV-2 infection. In vitro, ara-C and IdUrd were more active than ara-A, and PAA was least active. In female hamsters with genital HSV-2 infection, intravaginal treatment with PAA or ara-A was more effective than either ara-C or IdUrd.

Effects of streptovaricins and their degradation products on infectivity of Rauscher leukemia virus.

The virucidal effects of streptovaricin (Sv) A, SvC, SvD, streptoval (Sval) C, Sval Fc, and streptovarone were evaluated by incubation of the drug with Rauscher leukemia virus (RLV) at 37 degrees C for 60 minutes prior to dillution and addition to cells (in vitro assay) or before ip injection into animals (in vivo assay). The in vitro and in vivo assays were plaque formation and splenomegaly, respectively. A dose-related effect was observed with all six compounds with the in vitro assay.

Influenza virus infection of hamsters. A model for evaluating antiviral drugs.

Inoculation of hamsters with influenza virus [A/PR/8/34 HON 1] produces an inapparent infection which can be monitored by virus titrations of nasal washes or of homogenates prepared from trachea or lung. Antibody can be detected in the serum within 7 days following virus inoculation. Hamsters previously infected were found to be resistant to challenge with the same virus.

Pathogenesis of herpes simplex virus types 1 and 2 in mice after various routes of inoculation.

The pathogenesis of herpes simplex virus (HSV) types 1 and 2 was compared after inoculation of mice by different routes. Intravaginal inoculation of HSV-1 and HSV-2 produced a local infection, with virus recovery from the vagina through 5 days. Virus was recovered from the spinal cords 4 to 5 days after inoculation but not from liver, kidney, lung, spleen, or blood.

Genital infection of female hamsters with herpesvirus hominis type 2 (HVH-2).

Intravaginal inoculation of female hamsters (40-65 g) with HVH-2 (6 X 105 PFU) results in an infection of 40-67% of the animals. The illness is characterized by vaginitis with discharge, paralysis, and finally death. Washing the vagina with saline 30 min prior to virus inoculation enhances the infection so that 80-100% of the animals eventually die.

Inactivation of myxoviruses by calcium elenolate.

Calcium elenolate inactivates all myxoviruses so far tested. The pH of the reaction mixture is less critical for myxovirus inactivation than that required for coxsackie A-21 virus; the myxoviruses are inactivated at a broad spectrum of pH with the maximum activity occurring at a pH below 7.0.

Antiviral activity of cytarabine in herpesvirus-infected rats.

Intranasal inoculation of herpesvirus (approximately 1.8 mean lethal doses [LD(50)] in 0.1 ml) into 105- to 115-g rats produces paralytic disease in 4 to 5 days and 80 to 100% mortality in 8 to 12 days.