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mTOR inhibition and p53 activation, microRNAs: The possible therapy against
pandemic COVID-19
#MMPMID32835132
Ramaiah MJ
Gene Rep
2020[Sep]; 20
(?): 100765
PMID32835132
show ga
mTOR is a serine-threonine kinase and participates in cell proliferation,
cellular metabolism was found to be activated during Severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2) viral infection and replication. During viral
replication mTOR, downstream target genes such as ribosomal protein S6 kinase
beta 1 (S6K1) and Eukaryotic translational initiation factor 4E-binding protein1
(4-E-BP1) are activated result in ribosome biosynthesis and efficient protein
synthesis. In plasmacytoid dendritic cells (pDCs), mTOR plays a key role in the
association of adapter protein myeloid differentiation primary response gene 88
(MyD88), Toll-like receptor 9 (TLR9) and interferon regulatory factor (IRF-7)
leading to the transcriptional activation of type-I interferon (IFN) genes.
Viruses also inactivate the interferon ? (IFN-?) pathway by impairing the IRF-7
mediated activation of IFN-? gene transcription. Thus, mammalian target of
rapamycin (mTOR) inhibitors can help in suppressing the early stages of viral
infection and replication. Interestingly, the key tumor-suppressor p53 protein
will undergo degradation by virus-encoded E3 ubiquitin ligase Ring-finger and CHY
zinc-finger domain-containing 1 (RCHY1) leading to an increased viral survival in
host cells. Thus, the mTOR inhibitors and p53 activators or microRNAs that
functions as p53 and can target 3'-UTR of mTOR and RPS6KB1 might effectively
inhibit viral replication in the human respiratory tract and lung cells.
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