Method for inhibition of viral morphogenesis 机翻标题: 暂无翻译,请尝试点击翻译按钮。

公开号/公开日
CA2136958 A1 1993-12-09 [CA2136958]CA2136958 C 2011-03-22 [CA2136958] / 1993-12-092011-03-22
申请号/申请日
1993CA-2136958 / 1993-06-01
发明人
GLENN JEFFREY S;
申请人
GLENN JEFFREY S;
主分类号
IPC分类号
A01N-037/18A61K-031/365A61K-038/00A61K-038/07A61K-045/00A61P-031/12C07K-014/005C07K-014/08C12N-007/04C12N-007/06C12Q-001/02C12Q-001/18C12Q-001/68C12Q-001/70G01N-033/15G01N-033/50G01N-033/569G01N-033/576
摘要
(CA2136958) Viral morphogenesis, production, release or uncoating can be inhibited by effecting inhibition of prenylation of, or inhibition of post-prenylation reactions of, at least one viral protein.  The use of inhibitors of prenylation, and post-prenylation reactions, for example, inhibitors of the mevaloriate and prenyl group synthesis pathways, inhibitors of prenyl group transferases and mimics of the prenylation target CXXX (SEQ ID NO:1) box are disclosed.
机翻摘要
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地址
代理人
代理机构
;
优先权号
1992US-07890754 1992-05-29 1993WO-US05247 1993-06-01
主权利要求
(CA2136958)  Claims 1. A method to inhibit virion morphogenesis, production, release or uncoating which method comprises in vitro contacting animal cells infected with a virus that depends on prenylation for viral morphogenesis, production, release or uncoating with an effective amount of an agent which specifically inhibits prenylation or post-prenylation reactions of at least one viral protein required for viral morphogenesis, production, release or uncoating. 2. The method of claim 1, wherein the virus is herpes virus or Asian influenza virus. 3. The method of claim 1, wherein said virion is hepatitis D virus (HDV) and said viral protein is the large delta antigen of said HDV. 4. The method of claim 1, wherein said virion is human immunodeficiency virus and said viral protein is the nef protein. 5. The method of claim 3, wherein said inhibition is effected by a transdominant inhibitor of replication modified to resist prenylation. 6. The method of any one of claims 1 through 4, wherein said agent is an inhibitor of prenyl group synthesis or wherein said agent is an inhibitor of a prenyl transferase, or wherein said agent mimics a prenyl group or wherein said agent mimics the prenylation locus of the viral protein. 7. The method of claim 6, wherein the prenyl transferase is a farnesyltransferase. 8. The method of claim 6, wherein the prenyl transferase is a geranylgeranyltransferase. 9. The method of any one of claims 1 through 8, wherein said at least one viral protein contains a C-terminal amino acid sequence of the formula CXXX, XCXX, XXCX or XXXC (SEQ ID NO.:1, SEQ ID NO:4, SEQ ID NO:5 or SEQ ID NO:6) wherein C is cysteine and each X is independently any amino acid. 10. The method of claim 9, wherein said agent mimics said CXXX, XCXX, XXCX or XXXC (SEQ ID NO.:1, SEQ ID NO:4, SEQ ID NO:5 or SEQ ID NO:6). 11. The method of any one of claims 1 through 9, wherein said agent interferes with a post-prenylation reaction. 12. A method to screen candidate drugs as prenylation inhibitors which method comprises contacting cells which secrete or which have been modified to secrete a first protein containing a "CXXX" (SEQ ID NO:1) box and a second control protein wherein secretion of said first protein is dependent on prenylation and secretion of said second control protein is not dependent on prenylation, with said candidate drug under conditions wherein said control second protein is secreted, and determining the presence, absence or amount of said first protein secreted from said cells, wherein a candidate drug which decreases or abolishes the amount of secreted first protein is said effective prenylation inhibitor. 13. The method of claim 12, wherein said first protein is the large delta antigen of HDV. 14. The method of claim 12, wherein said first protein is a chimera consisting of a natively secreted protein which has been modified to contain, in place of its "CXXX" (SEQ ID NO:1) box, the "CXXX" (SEQ ID NO:1) box of a different protein. 15. Use of an agent effective to specifically inhibit prenylation or post-prenylation reactions of a protein in an animal virus that depends on the prenylation for viral morphogenesis, production, release or uncoating, in an amount effective to specifically inhibit the prenylation or the post-prenylation reactions of a protein in said virus in the manufacture of a medicament for inhibiting morphogenesis, production, release or uncoating of said virus. 16. The use of an agent effective to specifically inhibit prenylation or post-prenylation reactions of a protein according to claim 15, wherein said agent is an inhibitor of prenyl group synthesis or wherein said agent is an inhibitor of a prenyl transferase, or wherein said agent mimics a prenyl group or wherein said agent mimics the prenylation locus of the viral protein. 17. The use of an agent effective to specifically inhibit prenylation or post-prenylation reactions of a protein according to claim 16, wherein the prenyl transferase is a farnesyltransferase. 18. The use of an agent effective to specifically inhibit prenylation or post-prenylation reactions of a protein according to claim 16, wherein the prenyl transferase is a geranylgeranyltransferase. 19. The use of an agent effective to specifically inhibit prenylation or post-prenylation reactions of a protein according to any one of claims 15 through 18, wherein said agent interferes with a post-prenylation reaction. 20. The use of an agent effective to specifically inhibit prenylation or post-prenylation reactions of a protein according to any one of claims 15 through 19, wherein said viral protein contains a C-terminal amino acid sequence of the formula CXXX, XCXX, XXCX or XXXC (SEQ ID NO.:1, SEQ ID NO:4, SEQ ID NO:5 or SEQ ID NO:6) wherein C is cysteine and each X is independently any amino acid. 21. The use of an agent effective to specifically inhibit prenylation or post-prenylation reactions of a protein according to claim 20, wherein said agent mimics said CXXX, XCXX, XXCX or XXXC (SEQ ID NO.:1, SEQ ID NO:4, SEQ ID NO:5 or SEQ ID NO:6). 22. The use of an agent effective to specifically inhibit prenylation or post-prenylation reactions of a protein according to any one of claims 15 through 19, wherein said virion is hepatitis D virus (HDV) and said viral protein is the large delta antigen of said HDV. 23. The use of an agent effective to specifically inhibit prenylation or post-prenylation reactions of a protein according to claim 22, wherein said inhibition is effected by a transdominant inhibitor of replication modified to resist prenylation. 24. The use of an agent effective to specifically inhibit prenylation or post-prenylation reactions of a protein according to any one of claims 15 through 19, wherein said virion is human immunodeficiency virus and said viral protein is the nef protein. 25. The use of an agent effective to specifically inhibit prenylation or post-prenylation reactions of a protein according to any one of claims 15 through 24, wherein said virus is contained in an animal subject. 26. Use of an agent effective to specifically inhibit prenylation or post-prenylation reactions of a protein in an animal virus that depends on the prenylation for viral morphogenesis, production, release or uncoating, in an amount effective to specifically inhibit the prenylation or the post-prenylation reactions of a protein in said virus, for inhibiting morphogenesis, production, release or uncoating of said virus in an animal. 27. The use of an agent effective to specifically inhibit prenylation or post-prenylation reactions of a protein according to claim 26, wherein said agent is an inhibitor of prenyl group synthesis or wherein said agent is an inhibitor of a prenyl transferase, or wherein said agent mimics a prenyl group or wherein said agent mimics the prenylation locus of the viral protein. 28. The use of an agent effective to specifically inhibit prenylation or post-prenylation reactions of a protein according to claim 27, wherein the prenyl transferase is a farnesyltransferase. 29. The use of an agent effective to specifically inhibit prenylation or post-prenylation reactions of a protein according to claim 27, wherein the prenyl transferase is a geranylgeranyltransferase. 30. The use of an agent effective to specifically inhibit prenylation or post-prenylation reactions of a protein according to any one of claims 26 through 29, wherein said agent interferes with a post-prenylation reaction. 31. The use of an agent effective to specifically inhibit prenylation or post-prenylation reactions of a protein according to any one of claims 26 through 30, wherein said viral protein contains a C-terminal amino acid sequence of the formula CXXX, XCXX, XXCX or XXXC (SEQ ID NO.:1, SEQ ID NO:4, SEQ ID NO:5 or SEQ ID NO:6) wherein C is cysteine and each X is independently any amino acid. 32. The use of an agent effective to specifically inhibit prenylation or post-prenylation reactions of a protein according to claim 31, wherein said agent mimics said CXXX, XCXX, XXCX or XXXC (SEQ ID NO.:1, SEQ ID NO:4, SEQ ID NO:5 or SEQ ID NO:6). 33. The use of an agent effective to specifically inhibit prenylation or post-prenylation reactions of a protein according to any one of claims 26 through 30, wherein said virion is hepatitis D virus (HDV) and said viral protein is the large delta antigen of said HDV. 34. The use of an agent effective to specifically inhibit prenylation or post-prenylation reactions of a protein according to claim 33, wherein said inhibition is effected by a transdominant inhibitor of replication modified to resist prenylation. 35. The use of an agent effective to specifically inhibit prenylation or post-prenylation reactions of a protein according to any one of claims 26 through 30, wherein said virion is human immunodeficiency virus and said viral protein is the nef protein. 36. The use of an agent effective to specifically inhibit prenylation or post-prenylation reactions of a protein according to any one of claims 26 through 35, wherein said virus is contained in an animal subject.
法律状态
(CA2136958) LEGAL DETAILS FOR CA2136958  Actual or expected expiration date=2012-06-01    Legal state=DEAD    Status=LAPSED     Event publication date=1993-06-01  Event code=CA/APP  Event indicator=Pos  Event type=Examination events  Application details  Application country=CA CA2136958  Application date=1993-06-01  Standardized application number=1993CA-2136958     Event publication date=1993-12-09  Event code=CA/A1  Event type=Examination events  Application laid open  Publication country=CA  Publication number=CA2136958  Publication stage Code=A1  Publication date=1993-12-09  Standardized publication number=CA2136958     Event publication date=2000-05-11  Event code=CA/EEER  Event indicator=Pos  Event type=Examination events  Examination request    Event publication date=2011-03-22  Event code=CA/C  Event indicator=Pos  Event type=Event indicating In Force  Patent (second level)  Publication country=CA  Publication number=CA2136958  Publication stage Code=C  Publication date=2011-03-22  Standardized publication number=CA2136958     Event publication date=2012-06-01  Event code=CA/MKLA  Event indicator=Neg  Event type=Event indicating Not In Force  Lapsed
专利类型码
A1C
国别省市代码
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