Abstract | BACKGROUND: RESULTS: We used diverse cell lines (HK-2, Huh-7, HUVEC, Caco-2, and BEAS-2B) to analyze the effect of VPA and other HDAC inhibitors on the expression of the ACE-2 and NRP-1 receptors and their ability to inhibit infectivity, viral production, and the inflammatory response. Treatment with VPA significantly reduced expression of the ACE2 and NRP1 host proteins in all cell lines through a mechanism mediated by its HDAC inhibitory activity. The effect is maintained after SARS-CoV-2 infection. Consequently, the treatment of cells with VPA before infection impairs production of SARS-CoV-2 infectious viruses, but not that of other ACE2- and NRP1-independent viruses (VSV and HCoV-229E). Moreover, the addition of VPA 1 h post- infection with SARS-CoV-2 reduces the production of infectious viruses in a dose-dependent manner without significantly modifying the genomic and subgenomic messenger RNAs (gRNA and sg mRNAs) or protein levels of N protein. The production of inflammatory cytokines (TNF-α and IL-6) induced by TNF-α and SARS-CoV-2 infection is diminished in the presence of VPA. CONCLUSIONS: Our data showed that VPA blocks three essential processes determining the severity of COVID-19. It downregulates the expression of ACE2 and NRP1, reducing the infectivity of SARS-CoV-2; it decreases viral yields, probably because it affects virus budding or virions stability; and it dampens the triggered inflammatory response. Thus, administering VPA could be considered a safe treatment for COVID-19 patients until vaccines have been rolled out across the world.
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Authors | Maria Laura Saiz, Marta L DeDiego, Darío López-García, Viviana Corte-Iglesias, Aroa Baragaño Raneros, Ivan Astola, Victor Asensi, Carlos López-Larrea, Beatriz Suarez-Alvarez |
Journal | Clinical epigenetics
(Clin Epigenetics)
Vol. 13
Issue 1
Pg. 187
(10 11 2021)
ISSN: 1868-7083 [Electronic] Germany |
PMID | 34635175
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2021. The Author(s). |
Chemical References |
- Antiviral Agents
- Enzyme Inhibitors
- Receptors, Virus
- Neuropilin-1
- Valproic Acid
- Angiotensin-Converting Enzyme 2
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Topics |
- Angiotensin-Converting Enzyme 2
(drug effects, genetics)
- Antiviral Agents
(pharmacology)
- COVID-19
(prevention & control)
- Cells, Cultured
- Enzyme Inhibitors
(pharmacology)
- Epigenesis, Genetic
(genetics, physiology)
- Humans
- Neuropilin-1
(drug effects, genetics)
- Receptors, Virus
(drug effects)
- SARS-CoV-2
- Valproic Acid
(pharmacology)
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