Oral treatment of mice, cutaneously infected with herpes simplex virus type 1 (HSV-1) (strain SC16), with the α-gluco-sidase 1 inhibitor 6-O-butanoyl castanospermine (MDL 28,574) produced a significant delay in lesion development and reduced the amount of virus recovered from the brain. Virus load in the brains of mice, whose treatment started 2 days prior to infection, was reduced ˜100-fold when compared to untreated controls. Treatment initiated at the time of infection, while less effective than pre-treatment, nevertheless reduced virus recovery from the brain by 10-fold. Consistent with its antiviral activity, orally administered MDL 28,574 was rapidly incorporated by brain tissue and mice fed with compound over extended periods maintained relatively high levels of drug at this site.
Abstract Co-toxicity of fenpropathrin with deltamethrin 10 EC, esfenvalerate 5.5 EC, λ-cyhalothrin 2.5 EC and β-cyfluthrin was evaluated in field-collected and laboratory-reared populations of Lapaphis erysimi Kalt. Field population was found to be resistant to all these types of pyrethroids and RR (resistance ratio) was 31, 33, 33, 16 and 16 to fenpropathrin, deltamethrin, esfenvalerate, cyhalotiirn and β-cyfluthrin, respectively. Mixture of fenpropathrin with deltamethrin, esfenvalrate, λ-cyhalothirn and β-cyfluthrin in 1:1 ratio. Combination index and synergistic ratio have exhibited synergism of pyrethroid mixture. The results are discussed in relation to mechanism of synergism and practical implication of such mixture for mitigation of resistance in aphids. Keywords: Synergism, pyrethroids, type I, type II, aphids, insecticide, resistance Cite this Article Ahmed S., Asif MU., Nisar MS., Arshad M. et al. Co-Toxicity of Pyrethroid Mixtures against Field and Laboratory Reared Populations of Lipaphis erysimi Kalt. (Aphididae: Homoptera). Research & Reviews: Journal of Crop Science and Technology (RRJoCST). 2015; 4(1): 28–33p.
MDL 74968 (9-[2-methylidene-3-(phosphonomethoxy)-propyl]guanine), a novel acyclonucleotide derivative of guanine, inhibited human immunodeficiency virus type 1 (HIV-1) replication in vitro with activity comparable to that of adefovir (PMEA; 9-(2-phosphonomethoxyethyl)adenine). MDL 74968 was investigated in combination with two licensed nucleoside analogues, zidovudine and didanosine, using a cell viability assay, and drug interactions were evaluated by the isobologram technique, by calculating combination indices and by the MacSynergy™ program. Inhibition of HIV-1 replication was only additive in both cases. MDL 74968 had equivalent antiviral activity against strains of HIV-1 HXB2 engineered to have mutations which conferred resistance to the nucleoside analogues lamivudine, didanosine and zidovudine and the non-nucleoside inhibitor of reverse transcriptase (RT) nevirapine, as against the wild type strain. Continued passage of HIV-1 RF in C8166 cells in the presence of MDL 74968 for 5 months (30 passages) failed to select drug resistant mutants. Continued passage of virus in the presence of the same concentration of adefovir for the same length of time selected a virus in a single culture, which was 3-fold resistant to adefovir and cross-resistant to MDL 74968. Genotypic characterization of this virus revealed a lysine to arginine exchange (AAA to AGA) at position 65 in the RT gene. This virus was not cross-resistant to either zidovudine or nevirapine but showed reduced sensitivity to zalcitabine, didanosine and lamivudine. Continued passage of HIV-1 RF in the presence of nevirapine or zidovudine, using similar experimental protocols selected drug resistant viruses after eight and 17 passages, respectively, but these viruses remained sensitive to adefovir and MDL 74968.
A novel low-molecular-weight sulfonic acid polymer, MDL 101028, was investigated for antiviral activity against herpes simplex virus (HSV) type 1 and type 2 in human embryonic diploid fibroblasts (MRC-5) and in a line of monkey kidney cells (Vero). Potent antiviral activities were obtained when treatment was restricted to the adsorption phase of virus propagation as measured by plaque reduction assay, and this was confirmed by experiments at high multiplicity of infection. Inhibition of virus binding to host cells by MDL 101028 was compared to that of heparin, a known antagonist of virus attachment. Both compounds showed dose-dependent inhibition, with IC 50 values of 1.1 and 0.43 μg ml −1 , respectively. The effect on cell-to-cell fusion was investigated using a syncytial-positive (syn + ) phenotypic mutant of HSV-1 (strain 17i). MDL 101028 (3-1 μm) dramatically halted the spread of syncytial lesions; this effect was accompanied by the destruction of the syncytium and regrowth into the lesion by uninfected Vero cells. In contrast, heparin (10 μg ml −1 ) only partially reduced the spread of syncytia. Protection was also observed with MDL 29797 (100 μg ml −1 ), an antagonist of glycoprotein maturation. Unexpectedly, only a marginal effect was observed with acyclovir (10 μg ml −1 ), a potent inhibitor of viral DNA synthesis and HSV growth. As an extension to the current therapy for herpes simplex infection, acyclovir, the potent anti-fusion activity of MDL 101028 may have a clinical use in tissues or organs in which cell-to-cell fusion contributes to the pathology.
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