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Author Spotlight: Advancing Real-Time cAMP Detection in Cells Using cADDis Biosensor
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SARS-CoV-2 infection activates CREB/CBP in cellular cyclic AMP-dependent pathways
Qi Yang1,2, Jielin Tang1,2,3, Juan Cao2
1Chen Xinwen Lab in Department of Basic Research, Guangzhou Laboratory, Guangzhou, China.
Journal of Medical Virology
|December 8, 2022
Summary
Researchers found that the cAMP-PKA pathway and CREB/CBP interaction are crucial for SARS-CoV-2 infection. Targeting this interaction with naphthol AS-E shows promise for treating COVID-19, including variants.
Area of Science:
- Virology
- Molecular Biology
- Drug Discovery
Background:
- The COVID-19 pandemic, caused by SARS-CoV-2, necessitates understanding host-virus interactions for pathogenesis.
- Host-virus interactions remain incompletely understood, hindering effective therapeutic development.
Purpose of the Study:
- To investigate the role of host-associated signaling pathways in SARS-CoV-2 infection.
- To identify potential therapeutic targets for COVID-19 by analyzing host-virus interactions.
Main Methods:
- Transcriptomics analysis to identify relevant host signaling pathways.
- Gene knockdown using small interfering RNAs (siRNAs) to assess the role of CREB and CBP.
- Antiviral assays to evaluate the efficacy of naphthol AS-E against SARS-CoV-2 wild-type and variants.
Main Results:
- The cAMP-PKA pathway and CREB/CBP interaction are implicated in SARS-CoV-2 infection.
- Knockdown of CREB and CBP significantly inhibited the replication of SARS-CoV-2 Delta and Omicron BA.5 variants.
- Naphthol AS-E demonstrated potent inhibition of SARS-CoV-2 WT, Delta, Omicron BA.2, and BA.5 infections, with favorable EC50 values.
Conclusions:
- The CREB/CBP interaction, induced by the cAMP-PKA pathway, plays a critical role in SARS-CoV-2 pathogenesis.
- Targeting the CREB/CBP interaction presents a novel therapeutic strategy for COVID-19 treatment, including against emerging variants.
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