2002 Fiscal Year Final Research Report Summary
Basic Study on the protection of virus infection coinfected with MRSA.
| Project/Area Number |
13670141
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Kobe University |
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Principal Investigator |
HIJIKATA Akiko Kobe University, School of Medicine, Associate Professor, 医学部, 助教授 (10107948)
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| Co-Investigator(Kenkyū-buntansha) |
KONISHI Eiji Kobe University, School of Medicine, Associate Professor, 医学部, 助教授 (40135786)
KATAOKA Nobumasa Kobe University, School of Medicine, Associate Professor, 医学部, 助教授 (80071398)
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| Project Period (FY) |
2001 – 2002
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| Keywords | protease / virus / plasmin / inhibitor / infection |
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| Research Abstract |
This study was undertaken to clarify the possible role of proteases of Staphylococcus aureus and the coagulation/fibrinolysis enzymes activated by the S.a aureus proteases in the viral infection, and to evaluate the efficacy of protease inhibitors in the protection of viral infection.
First, we studied the activation of Sendai virus by serine proteases and its inhibition by synthetic inhibitors using LLC-MK_2 cells. Treatment with plasmin and trypsin increased the infective titers of Sendai virus dose-dependently, whereas thrombin and tryptase had no detectable effect on activation within a dose range used in the present study. PASI535 (Nα- (4-aminomethylbenzoyl) -4- (3-picoryloxy)- L-phenylalanine n-hexyl-amide) and MNAPPA ((2R,4R) -4-Phenyl-[Nα- (7-methoxy-2-naphthalene-sulfonyl) -L-arginyl]-2-piperidinecarboxylic acid), active site-directed inhibitors of plasmin and trypsin respectively, inhibited plasmin-induced and trypsin-induced virus activation of Sendai virus. The present study
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provided an experimental basis for potential use of active site-directed synthetic inhibitors as preventive tools for viral infection in vitro.
Second, we studied the protease activity of culture supernatant of S.auzeus obtained from urine of a patient suffering from urinary tract infection. The amidase activity and clotting activity revealed after the addition of ammonium sulfate fraction of the culture supernatant and euglobulin fraction of human plasma together, while these activities of ammonium sulfate fraction or euglobulin traction alone were undetectable or negligible small. The synthetic thrombin inhibitor argatroban ((2R, 4R) -l-[N^2- (3-methyl-l, 2, 3, 4-tetrahydro-8- quinolinesulfonyl) -L-arginyl]-4-methyl-2-piperidinecarboxylic acid) has been clinically used as a therapeutic remedy for the treatment of thrombotic disorders. We found a new effect of argatroban as a potent staphylothrombin inhibitor to inhibit fibrin formation induced by Staphylococcus aureus. Potent staphylothrombin inhibitor would be a useful tool to clarify and evaluate the role of coagulase/staphylothrombin/fibrin in the pathogenesis of S.aureus. Less
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