Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, we have generated and characterized an avian influenza H5N1 hemagglutinin (HA), neuraminidase (NA) and M2 ion channel pseudotyped HIV-based vector system (HaNaM-pseudotyped HIV vector). The cleavage site of the HA protein was modified to necessitate trypsin-dependent maturation of the glycoprotein. HA, NA and M2 were efficiently incorporated in HIV vector particles which could transduce different cell lines in a trypsin-dependent manner. Results also showed that the presence of avian influenza M2 and NA proteins maximized both vector production and transduction and that transduction was highly sensitive to the specific NA inhibitor oseltamivir (Tamiflu). H5N1 HaNaM-pseudotyped HIV vector system was also adapted for cell-based high throughput screening of drug candidates against influenza virus infection, and its high sensitivity to the specific oseltamivir validates its potential utility in the identification of new influenza inhibitors. Overall, the trypsin-dependent H5N1-pseudotyped HIV vector can mimic avian influenza virus infection processes with sufficient precision to allow for the identification of new antivirals and to study avian influenza virus biology in a lower biosafety level laboratory environment.
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PMID:Characterization of a trypsin-dependent avian influenza H5N1-pseudotyped HIV vector system for high throughput screening of inhibitory molecules. 1835 97

In 2009, a pandemic novel influenza virus (H1N1) outbreak was declared by the World Health Organization and resulted in significant worldwide illness. This report describes a 50-year-old male with end-stage lung disease secondary to alpha(1)-anti-trypsin deficiency and chronic obstructive pulmonary disease. He was admitted for potential bilateral lung transplantation when suitable organs became available. Incidentally, he was found to have some non-specific symptoms, including malaise and myalgias. These findings were attributed to killed-virus H1N1 vaccine given 48 hours earlier. However, as a safety measure, a nasopharyngeal swab was taken, and anti-viral therapy with oseltamivir (Tamiflu) was started empirically. He underwent bilateral lung transplantation on the same day of admission. In the immediate post-operative period his nasopharyngeal swab came back positive for H1N1 influenza virus. Then, post-operatively, two consecutive bronchoalveolar lavage samples from the transplanted lungs were found to be positive for H1N1 virus. He received three-weeks of antiviral treatment post-operatively and he had uneventful procedure with favorable outcome.
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PMID:Successful bilateral lung transplantation in a patient with end-stage lung disease and positive novel influenza virus (H1N1). 2053 89

Influenza virus is activated by proteolytic cleavage of hemagglutinin by trypsin. After determining the optimal trypsin concentration, intracellular and extracellular influenza A/PR/8/34 (H1N1) and A/Victoria/361/2011 (H3N2) virus productions were compared in cultures treated with T-705 (favipiravir) and GS 4071 (an active form of oseltamivir). Although both drugs efficiently inhibited extracellular viral RNA release in a dose-dependent manner, T-705 inhibited it to the level of the inoculum without trypsin treatment, while GS 4071 inhibited it to a final level 10 times higher than that without trypsin. T-705 inhibited intracellular viral RNA production to the level of input virus in both trypsin-treated and untreated cells. In contrast, GS 4071 dose-dependently inhibited intracellular viral RNA production in cells treated with trypsin but allowed viral RNA synthesis. The level of maximum inhibition by GS 4071was 10 times higher than that of cells without trypsin and 1,000 times greater than the inoculum titer in cells without trypsin. T-705 inhibited both intracellular and extracellular virus production 1,000 and 10 times more strongly, respectively, than GS 4071. T-705 has powerful anti-influenza activity in the absence of trypsin and even in the trypsin-optimized growth condition, suggesting the therapeutic advantage in treatment of influenza complicated with bacterial pneumonia. Keywords: influenza; T-705; Tamiflu; trypsin; bacterial trypsin-like protease.
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PMID:Growth activation of influenza virus by trypsin and effect of T-705 (favipiravir) on trypsin-optimized growth condition. 3150 97