Cholinergic α7 nAChR signaling suppresses SARS-CoV-2 infection and inflammation in lung epithelial cells
et al., Journal of Molecular Cell Biology, doi:10.1093/jmcb/mjad048, Jul 2023
HCQ for COVID-19
1st treatment shown to reduce risk in
March 2020, now with p < 0.00000000001 from 424 studies, used in 59 countries.
No treatment is 100% effective. Protocols
combine treatments.
6,300+ studies for
210+ treatments. c19early.org
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In vitro and mouse study showing that activating α7 nAChR with the agonist GTS-21 reduced oxidative stress and inflammation, and reduced live virus infection in lung epithelial cells.
The results provide some mechanistic insight into how HCQ may inhibit SARS-CoV-2 infection, by acting through the α7 nAChR pathway. Previous in silico studies predict HCQ blocks SARS-CoV-2 binding to both ACE2 and α7 nAChR. This study provides experimental evidence that activating α7 nAChR decreases ACE2 expression and reduces SARS-CoV-2 infection.
Activating the α7 nAChR pathway (with agonists) or protecting it from viral interference (with HCQ for example) could be viable therapeutic approaches against COVID-19.
39 preclinical studies support the efficacy of HCQ for COVID-19:
1.
Shang et al., Identification of Cathepsin L as the molecular target of hydroxychloroquine with chemical proteomics, Molecular & Cellular Proteomics, doi:10.1016/j.mcpro.2025.101314.
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8.
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9.
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10.
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11.
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12.
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13.
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14.
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16.
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17.
Wen et al., Cholinergic α7 nAChR signaling suppresses SARS-CoV-2 infection and inflammation in lung epithelial cells, Journal of Molecular Cell Biology, doi:10.1093/jmcb/mjad048.
18.
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19.
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20.
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21.
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22.
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23.
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24.
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25.
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26.
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34.
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Wen et al., 25 Jul 2023, peer-reviewed, 5 authors.
Contact: zhaojincun@gird.cn, xsu@ips.ac.cn.
Cholinergic α7 nAChR signaling suppresses SARS-CoV-2 infection and inflammation in lung epithelial cells
doi:10.1093/jmcb/mjad048/7231085
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced coronavirus disease 2019 (COVID-19) has caused more than 6 million deaths and poses a huge threat to the global economy and public health. SARS-CoV-2 enters lung epithelial cells depending on S protein binding with angiotensin converting enzyme 2 (ACE2). In-silico studies have shown that both SARS-CoV and SARS-CoV-2 S glycoproteins can interact with the extracellular domain of α7 nicotinic acetylcholine receptor (nAChR). Hydroxychloroquine, a known SARS-CoV-2 inhibitor, acts at the entry stage of SARS-CoV-2 by blocking the virus-binding sites on the two receptors, ACE2 and α7 nAChR (Navya and Hosur, 2021). Given that α7 nAChR possesses anti-inflammatory effects and could interact with the SARS-CoV-2 S protein,
References
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