Leronlimab Blockade Downregulates mTOR Disrupting

Leronlimab Blockade Downregulates mTOR Disrupting Viral Replication

I've developed a theory of a way that leronlimab may stop or slow down viral replication and act directly as an antiviral.

CCR5 blockade of CCL5 disrupts the mTOR/4E-BP1 pathway dysregulating elF4E. With elF4E disrupted the COVID-19 virus 5' -end cap it would be unable to separate it's mRNA and duplicate.

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CCL5-induced CCR5 signaling activates the mTOR/4E-BP1 pathway to directly modulate mRNA translation. Specifically, CCL5-mediated mTOR activation contributes to T cell chemotaxis by initiating the synthesis of chemotaxis-related proteins. These studies extend the role of CCL5 mediated CCR5 signaling beyond lymphocyte chemotaxis and demonstrate a role for chemokines in promoting glucose uptake and ATP production to match energy demands of migration.

Inhibition studies with the PI3K inhibitor LY294002 and the mTOR2 inhibitor rapamycin have underscored the importance of CCL5 activation of PI3K/mTOR signaling to induce protein synthesis. CCL5-mediated activation of CCR5 leads to the phosphorylation and deactivation of the translational repressor 4E-BP1 in a PI3K/mTOR-dependent manner, which results in the subsequent release of eukaryotic initiation factor-4E (eIF4E) ( . eIF4E binds the mRNA 5′-cap structure together with other initiation factors to form the eIF4F complex, responsible for mRNA unwinding and ribosomal binding during mRNA translation.

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[url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3436201/
]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3436201/
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CCR5 antagonists also disrupt the PI3K-AKT-mTORC1 pathway."

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https://www.researchgate.net/publication/3410...y_by_HIV-1

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However, we found a significant inhibition of HIF-1α through 24hpi and 48hpi of the infection, suggesting a crosstalk between the SARS-CoV-2 and the Akt/mTOR/HIF-1 signaling pathways. Inhibition of the mTOR signaling pathway using Akt inhibitor MK-2206 showed a significant reduction in virus production."

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https://www.tandfonline.com/doi/full/10.1080/...20.1799723

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Structural basis of RNA cap modification by SARS-CoV-2
To hijack the host translation machinery for propagation, enzymes encoded by the genome of coronaviruses (CoVs) modify the 5′-end of virally encoded mRNAs by creating a cap

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https://www.nature.com/articles/s41467-020-17496-8