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)

Several derivatives of K-252a, a protein kinase inhibitor isolated from Nocardiopsis sp., were investigated for their effects on the replication of vesicular stomatitis virus (VSV) in BHK-21 cell cultures. Among those we tested, KT5926, which preferentially inhibits the myosin light chain kinase (MLCK), suppressed the viral replication by 95-99% at 15 microM. K-252a, which inhibits a broad spectrum of cellular protein kinase, similarly affected the viral replication. Other derivatives, KT5720 and KT5823, that are known to inhibit the cAMP-dependent protein kinase (PKA) and cGMP-dependent protein kinase (PKG), respectively, did not suppress VSV replication even at a high concentration as 15 microM. None of these inhibitors affected the Sindbis virus replication in BHK-21 cells under similar assay conditions as used for VSV. KT5926 and K-252a seemed to affect the VSV replication at the step(s) after the viral invasion, resulting in decreased viral RNA synthesis. Neither substance inhibited cellular casein kinase (CK) II which is known to be involved in phosphorylation of the nonstructural (NS) protein, a non-catalytic subunit of the viral RNA polymerase. These results suggest that the inhibition of VSV replication by KT5926 and K-252a is not a secondary effect due to generalized suppression of host cell activities, and that the VSV replication requires the KT5926-sensitive function(s) in the cell which would be performed by an enzyme(s) other than CK II.
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PMID:Studies on the antiviral activity of protein kinase inhibitors against the replication of vesicular stomatitis virus. 755 Jan 28

We investigated the antiviral mechanisms of K-252a, a broad non-specific protein kinase inhibitor which was isolated from Nocardiopsis sp. and its derivative (KT5926), against vesicular stomatitis virus (VSV) replication in BHK-21 cells. Although K-252a (5 microM) and KT5926 (15 microM) similarly suppressed the viral primary and secondary transcriptions and genomic RNA synthesis in vivo, the inhibitory mechanisms did not seem to be the same; phosphorylation of the viral NS protein was suppressed by K-252a, which might account for the decreased viral RNA synthesis caused by K-252a. On the other hand, KT5926, being known to preferentially inhibit myosin light chain kinase (MLCK), had little effect on NS protein phosphorylation. Cellular casein kinase II, which is believed to be involved in the phosphorylation of the N-terminal side (domain I) of NS protein, was not inhibited at all by KT5926 even at 15 microM under in vitro assay conditions, and was only weakly inhibited by K-252a at 1 to 10 microM. Neither inhibitor seemed to directly affect viral protein synthesis, but affected it indirectly as a secondary effect of reduced viral RNA synthesis. These results suggest that both the KT5926-sensitive and the KT5926-resistant but K-252a-sensitive functions are involved in the essential processes of viral RNA synthesis. The KT5926-sensitive function(s) might not be involved in the NS protein phosphorylation, but may participate in some other way in the process of virus replication. On the other hand, the KT5926-resistant, K-252a-sensitive function(s) are probably involved in NS protein phosphorylation. The possible nature of those functions is discussed.
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PMID:Studies on the antiviral mechanisms of protein kinase inhibitors K-252a and KT5926 against the replication of vesicular stomatitis virus. 963 7