Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

TsG16(I) is a temperature-sensitive mutant of vesicular stomatitis virus. In vitro, at the permissive temperature (31 degrees), it makes long poly(A) tracts, shows a larger increase in polyadenylation in the presence of S-adenosyl-homocysteine than its parental wt(Glasgow) virus, and makes an excess of polycistronic mRNA. In vitro transcription is also more thermosensitive than that of wt virus. Previous work suggested that there are at least two mutations in the L gene of tsG16(I), one effecting the poly(A)-associated phenotypes, the polycistronic phenotype, and the ability to grow at 34.7 degrees, the other affecting in vitro thermosensitivity for transcription and ability to grow at 37 degrees. We report further characterization of two revertants: 35G16p25, which grows at 34.7 degrees and has regained the wt poly(A), SAH and polycistronic RNA phenotypes; and 37G16p25, isolated from 35G16p25 based on growth at 37 degrees, which has regained the wt phenotype for in vitro thermosensitivity of transcription. Both revertants were shown to be due to intracistronic reversion[s] in the L gene. Sequencing of the L genes indicated that the tsG16(I) poly(A), SAH, polycistronic RNA, and growth at 34.7 degrees phenotypes were associated with amino acid 1488 phenylalanine-->serine and that transcription thermosensitivity and growth at 37 degrees were associated with changes in cysteine 1291.
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PMID:Amino acid changes in the L polymerase protein of vesicular stomatitis virus which confer aberrant polyadenylation and temperature-sensitive phenotypes. 838 56

Ever since the S-adenosylhomocysteine (AdoHcy, SAH) hydrolase was recognized as a pharmacological target for antiviral agents (J. A. Montgomery et al., J. Med. Chem. 25:626-629, 1982), an increasing number of adenosine, acyclic adenosine, and carbocyclic adenosine analogues have been described as potent SAH hydrolase inhibitors endowed with broad-spectrum antiviral activity. The antiviral activity spectrum of the SAH hydrolase inhibitors include pox-, rhabdo-, filo-, arena-, paramyxo-, reo-, and retroviruses. Among the most potent SAH hydrolase inhibitors and antiviral agents rank carbocyclic 3-deazaadenosine (C-c3 Ado), neplanocin A, 3-deazaneplanocin A, the 5'-nor derivatives of carbocyclic adenosine (C-Ado, aristeromycin), and the 2-halo (i.e., 2-fluoro) and 6'-R-alkyl (i.e., 6'-R-methyl) derivatives of neplanocin A. These compounds are particularly active against poxviruses (i.e., vaccinia virus), and rhabdoviruses (i.e., vesicular stomatitis virus). The in vivo efficacy of C-c3 Ado and 3-deazaneplanocin A has been established in mouse models for vaccinia virus, vesicular stomatitis virus, and Ebola virus. SAH hydrolase inhibitors such as C-c3Ado and 3-deazaneplanocin A should in thefirst place be considered for therapeutic (or prophylactic) use against poxvirus infections, including smallpox, and hemorrhagic fever virus infections such as Ebola.
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PMID:John Montgomery's legacy: carbocyclic adenosine analogues as SAH hydrolase inhibitors with broad-spectrum antiviral activity. 1643 25