Synthesis and anti-HIV-1 activity of the conjugates of gossypol with oligopeptides and D-glucosamine

A series of novel gossypol derivatives were synthesized and screened for their in vitro anti-HIV- 1I activity. The results showed that replacing the aldehyde groups of gossypol with certain oligopeptides and Dglucosamine not only reduced the cytotoxicity of gossypol derivatives but also enhanced their antiviral activity against HIV-1. Interestingly, D-glucosamine derivative of gossypol that lacked the COONa group also exhibited the same potent anti-HIV-1 activity as oligopeptide derivatives with the COONa group. These compounds blocked the entry of HIV-1ⅢB into target cell. which was similar to T20. Furthermore, the molecular docking analysis rationalized their anti-HIV-1 activity. The results also implied that certain oligopeptides and D-glucosamine were important moities to prepare gossypol derivatives as HIV- 1 entry inhibitors besides certain amino acids.

Identification of the ryanodine receptor mutation I4743M and its contribution to diamide insecticide resistance in Spodoptera exigua (Lepidoptera: Noctuidae)

Insect ryanodine receptors(RyRs)are the targets of diamide insecticides.Two point mutations G4946E and I4790M(numbering according to Plutella xylostella,PxRyR)in the transmembrane domain of the insect RyRs associated with diamide resistance have so far been identified in three lepidopteran pests,P.xylostella,Tuta absoluta and Chilo suppressalis.In this study,we identified one of the known RyR target site resistance mutations(I4790M)in a field-collected population of Spodoptera exigua.The field-collected WF population of S.exigua exhibited 154 fold resistance to chlorantraniliprole when compared with the susceptible WH-S strain.Sequencing the transmembrane domains of S.exigua RyR(SeRyR)revealed that the resistant WF strain was homozygous for the 14743M mutation(corresponding to I4790M in PxRyR),whereas the G4900E allele(corresponding to G4946E of PxRyR)was not detected.The 4743M allele was introgressed into the susceptible WH-S strain by crossing WF with WH-S,followed by three rounds of backcrossing with WH-S.The introgressed strain 4743M was homozygous for the mutant 4743M allele and shared about 94%of its genetic background with that of the recipient WH-S strain.Compared with WH-S,the near-isogenic 4743M strain showed moderate levels of resistance to chlorantraniliprole(21 fold),cyantraniliprole(25 fold)and flubendiamide(22 fold),suggesting that the I4743M mutation confers medium levels of resistance to all three diamides.Genetic analysis showed diamide resistance in the 4743M strain was inherited as an autosomal and recessive trait.Results from this study have direct implications for the design of appropriate resistance monitoring and management practices to sustainably control S.exigua.

Heat shock cognate 71 (HSC71) regulates cellular antiviral response by impairing formation of VISA aggregates

In response to viral infection, RIG-I-like RNA helicases detect viral RNA and signal through the mitochondrial adapter protein VISA. VISA activation leads to rapid activation of transcription factors IRF3 and NF-κB, which collaborate to induce transcription of type I interferon (IFN) genes and cellular antiviral response. It has been demonstrated that VISA is activated by forming prion-like aggregates. However, how this process is regulated remains unknown. Here we show that overexpression of HSC71 resulted in potent inhibition of virus-triggered transcription of IFNB1 gene and cellular antiviral response. Consistently, knockdown of HSC71 had opposite effects. HSC71 interacted with VISA, and negatively regulated virus-triggered VISA aggregation. These findings suggest that HSC71 functions as a check against VISA-mediated antiviral response.

Genetic analysis and molecular detection of resistance to chlorpyrifos mediated by the A216S substitution in acetylcholinesterase-1 in the plant bug Apolygus lucorum

The green plant bug Apolygus lucorum is a major pest of Bacillus thuringiensis cotton in China.Previously,we reported that chlorpyrifos resistance in a laboratory-selected strain of A.lucorum(BZ-R)is associated with the homozygosis of an allele in the ace-1 gene encoding an alanine to serine substitution at position 216 of acetylcholinesterase-1.Here we describe the results of crosses between the resistant BZ-R strain(41-fold to chlorpyrifos)and the unselected susceptible BZ-S strain homozygous for the wild type alanine allele at position 216.Resistance to chlorpyrifos was inherited as a semi-dominant trait mainly controlled by a single autosomal gene and co-segregates strongly but not completely with the serine substitution in ace-1.Synergism bioassays and enzyme assays showed that minor contributions to resistance are also made by enhanced cytochrome P450 and carboxylesterase activities.A survey of 25 field populations from five Chinese provinces showed strong positive correlations between 50%lethal concentration against chlorpyrifos and S216 allele and genotype frequencies,although the most tolerant populations still only show 40%-50%S216 allele frequencies.The results above provide important information for designing effective resistance monitoring and management strategies for A.lucorum in China.