Influenza control drugs:research advances / 国际药学研究杂志

Drug control is still one of the main measures to control influenza. The current influenza prevention and treatment drugs mainly include M2 ion channel blockers and neuraminidase inhibitors. They have a certain therapeutic effect,but their resis?tance has also become increasingly prominent. In recent years,with the in-depth application of crystal lography,virology and other re?lated disciplines in the field of pharmacy,many new drugs have entered the(pre-)clinical test stage,and achieved good antiviral ef?fects. The most representatives include broad-spectrum anti-influenza virus hemagglutinin antibody and viral RNA polymerase complex small molecule inhibitors. Here,we introduce some new drugs against influenza so as to provide a reference for the prevention and con?trol of influenza epidemic.

Pathogenic mechanisms of influenza virus and Staphylococcus aureus co-infection:research progress / 军事医学

Studies have shown that co-infection of influenza viruses with bacteria is an important cause of high mortality during the epidemic of influenza.There are at least 12 species of bacteria that have been reported to be able to co-infect with influenza.Among those species,co-infection with Staphylococcus aureus is not only the most common but also the most lethal.However,the pathogenesis of high mortality from co-infection with influenza virus/S.aureus remains elusive.In addition,co-infection of influenza virus/S.aureus can induce severe pneumonia.There is new evidence that influenza virus can reduce the host′s tolerance to pathogenic or inflammatory injury,and the two pathogens can also synergistically aggravate toxic effects on the host.Here,we review the mechanisms of severe mortality of influenza infection associated with S.aureus co-infections in order to contribute to prevention and control of influenza in the future.

Role of complement activation and CVF intervention in lung inflammatory injury induced by influenza virus / 军事医学

Objective To investigate the mechanism of pulmonary inflammation induced by influenza virus , and provide reference for the development of effective drugs for viral pneumonia .Methods An influenza PR8 infection mouse model was established .The levels of inflammatory cytokines and complement molecules were determined using RT -PCR and ELISA.The pathological changes were examined using biopsy .The complement inhibitor cobra venom factor ( CVF) was injected intraperitoneally at a dose of 50 μg/( kg· 24 h) , and then body mass .The survival rate and inflammatory factors were examined .Results Compared with the control group , the expressions of complement regulatory molecule Crry and CD59 were significantly decreased (P<0.01), while those of complement C9 and complement receptor C3aR and C5aR were significantly increased in the lungs of influenza model mice (P<0.01).Pro-inflammatory cytokines TNF-α, IL-6 and IFN-γwere highly expressed , but anti-inflammatory cytokine IL-2 was lowly expressed in serum .Treatment with CVF caused a sight body mass loss, a survival rate increase and a lung index decrease (P <0.05).Moreover, an IL-2 expression increase and a decrease of IL-6, TNF -αand INF-γexpression were observed in CVF treatment mice ( P< 0.05).Conclusion Inhibition of complement activation can increase the survival rate of mice with influenza pneumonia and decrease pulmonary indexes .thus delaying the pathogenesis of PR 8.

An electrochemical biosensor based on a DNA tetrahedral nanostructure probe for the detection of Ebola virus nucleotide / 军事医学

Objective To establish a quick electrochemical biosensor for the detection of nucleic acid of Ebola virus . Methods The DNA tetrahedral nanostructure was self-assembled on gold surface by strong Au-S chemical bonds , leaving the target probe at the top .A biotinylated-ssDNA was introduced as the detection probe by specific binding of the captured target sequence , before avidin-horseradish peroxidase ( HRP) was used as a signal amplifier to transduce amperometric sig-nal through interactions with TMB substrate .Results The results indicated that the nucleotide sequence of Ebola virus could be recognized and detected by the sensor .The linear range for the detection of target DNA was from 1.0 ×10 -9 to 5.0 ×10 -6 mol/L,and the detection limit was 5.2 ×10 -10 mol/L.Conclusion The fabricated sensor is demonstrated to be sensitive and specific for the detection of Ebola virus nucleotide .

Detection and Genotyping of Herps Simplex Virus Type 2 by DNA Sequencing / 解放军医学杂志

Objective Herpes simplex virus is the pathogenic agent of human herpes simplex. There are two genotypes of herpes simplex virus, HSV-1 and HSV-2. The clinical manifestations of HSV-1 and HSV-2 overlap each other and it is difficult to differentiate them clinically. Methods developed based on genome differences are efficient ones to differentiate the two genotypes of HSV. In this study, we attempted to develop a new method to detection and genotyping human HSV in clinical samples. Methods Swab samples were collected from genital lesions of patients and placed in transport media. Samples were used to inoculate Vero cells. After appearance of the cytotoxicity, the infection mixtures were collected, and subjected to genomic DNA extraction. Based on the conservation and variation of gD of HSV-1 and HSV-2, a pair of primers amplifying both of them were designed and synthesized. Sequence of the virus were amplified and cloned into pMD-18T, and then the sequence was determined by DNA sequencing. The sequence was compared to all the known sequences in Genebank by using BLAST. According to the BLAST results, the genus and genotype of the virus was determined. Results A DNA fragment of about 200 bp was successfully amplified. This DNA fragment was cloned and sequenced. The sequence was compared with other known sequences. the results showed that this sequence had the highest homology to gD of HSV, indicating that the virus in the sample was HSV-2. The BLAST results also showed that there were some differences in the sequence of gD to those previously isolated. Conclusion DNA sequencing of PCR amplification products is an efficient and definite method to detect and genotype HSV-1 and HSV-2 which otherwise are difficult to differentiate clinically.

Screening,identification and sequencing of human phage engineered antibody against HBsAg / 解放军医学杂志

Objective To screen and identify the human phage engineered antibodies against HBsAg, and to analyze their gene sequence. Methods The phage antibody library was constructed by phage surface display techniques, and then the antibody genes were isolated and amplified from human peripheral blood lymphocyte. The human phage engineered antibody against HBsAg was selected through bio-panning from the phage antibody library. The affinity and specificity of the phage antibody was identified by ELISA and inhibition ELISA assay. The genes of heavy chain and light chain of the phage antibody against HBsAg were analyzed by sequencing. Results 30 colonies were obtained after three rounds of bio-panning. One of them had the highest A490 (A490=1.47?0.08) with ELISA, and the inhibition rate was 76% with inhibition assay (A490=0.35?0.10), implying that the phage antibody against HBsAg was of high specificity. The findings of enzyme digestion demonstrated that the phage antibody included genes of heavy chain and light chain. Sequencing results indicated that the VH region of heavy chain belonged to VHI subgroup and the VL region of light chain belonged to V? Ⅰ and V? Ⅲ subgroup. Conclusions The specific human phage engineered antibody against HBsAg was selected successfully from the phage antibody library. These results suggest that screening and identification of human phage engineered antibody against HBsAg through the phage antibody library are technologically feasible. It lays a foundation for application of human engineered antibody against HBsAg to design new targeted therapy strategy for HBV.