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All Studies   Meta Analysis       

Super-resolution imaging reveals the mechanism of endosomal acidification inhibitors against SARS-CoV-2 infection

Yan et al., ChemBioChem, doi:10.1002/cbic.202400404
Jun 2024  
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HCQ for COVID-19
1st treatment shown to reduce risk in March 2020, now with p < 0.00000000001 from 419 studies, recognized in 46 countries.
No treatment is 100% effective. Protocols combine treatments.
5,300+ studies for 115 treatments. c19hcq.org
In Vitro study showing that endosomal acidification inhibitors like HCQ minimize SARS-CoV-2 infection by blocking viral internalization and RNA release in cells expressing ACE2. Authors utilized super-resolution structured illumination microscopy (SIM) to analyze the effects of CQ, HCQ, Bafilomycin A1 (BafA1), and Dynasore on the endocytic processes of SARS-CoV-2. All four compounds inhibited the internalization and degradation of the RBD-ACE2 complex in living cells, with BafA1 showing the highest inhibition rate. The results confirm that endosomal acidification inhibitors can disrupt critical stages of SARS-CoV-2 infection within host cells.
See also Shang et al., an In Vitro and mouse study showing that endosomal acidification inhibitors CQ, bafilomycin A1, and NH4CL suppress SARS-CoV-2 replication and relieve viral pneumonia. Authors found that these compounds significantly reduced SARS-CoV-2 viral yields in Vero E6, Huh-7, and 293T-ACE2 cells. In hACE2 transgenic mice, CQ and bafilomycin A1 reduced viral replication in lung tissues and alleviated pneumonia with reduced inflammatory infiltration and improved alveolar structure.
38 preclinical studies support the efficacy of HCQ for COVID-19:
Yan et al., 14 Jun 2024, peer-reviewed, 7 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperHCQAll
DOI record: { "DOI": "10.1002/cbic.202400404", "ISSN": [ "1439-4227", "1439-7633" ], "URL": "http://dx.doi.org/10.1002/cbic.202400404", "abstract": "<jats:p>In this study, super‐resolution structured illumination microscope (SIM) was used to analyze molecular mechanism of endocytic acidification inhibitors in the SARS‐CoV‐2 pandemic, such as Chloroquine (CQ), Hydroxychloroquine (HCQ) and Bafilomycin A1 (BafA1). We fluorescently labeled the SARS‐CoV‐2 RBD and its receptor ACE2 protein with small molecule dyes. Utilizing SIM imaging, the real‐time impact of inhibitors (BafA1, CQ, HCQ, Dynasore) on the RBD‐ACE2 endocytotic process was dynamically tracked in living cells. Initially, the protein activity of RBD and ACE2 was ensured after being labeled. And then our findings revealed that these inhibitors could inhibit the internalization and degradation of RBD‐ACE2 to varying degrees. Among them, 100 nM BafA1 exhibited the most satisfactory endocytotic inhibition (~63.9%) and protein degradation inhibition (~97.7%). And it could inhibit the fusion between endocytic vesicles in the living cells. Additionally, Dynasore, a widely recognized dynein inhibitor, also demonstrated cell acidification inhibition effects. Together, these inhibitors collectively hinder SARS‐CoV‐2 infection by inhibiting both the viral internalization and RNA release. The comprehensive evaluation of pharmacological mechanisms through super‐resolution fluorescence imaging has laid a crucial theoretical foundation for the development of potential drugs to treat COVID‐19.</jats:p>", "alternative-id": [ "10.1002/cbic.202400404" ], "assertion": [ { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Received", "name": "received", "order": 0, "value": "2024-05-02" }, { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Accepted", "name": "accepted", "order": 1, "value": "2024-06-14" }, { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Published", "name": "published", "order": 2, "value": "2024-06-14" } ], "author": [ { "affiliation": [ { "name": "Dalian Institute of Chemical Physics department of biotechnology CHINA" } ], "family": "Yan", "given": "Chunyu", "sequence": "first" }, { "affiliation": [ { "name": "Dalian Institute of Chemical Physics department of biotechnology CHINA" } ], "family": "Zhou", "given": "Wei", "sequence": "additional" }, { "affiliation": [ { "name": "Dalian Institute of Chemical Physics department of biotechnology CHINA" } ], "family": "Zhang", "given": "Yan", "sequence": "additional" }, { "affiliation": [ { "name": "Dalian Institute of Chemical Physics department of biotechnology CHINA" } ], "family": "Zhou", "given": "Xuelian", "sequence": "additional" }, { "affiliation": [ { "name": "Dalian Institute of Chemical Physics department of biotechnology CHINA" } ], "family": "Qiao", "given": "Qinglong", "sequence": "additional" }, { "affiliation": [ { "name": "Dalian Institute of Chemical Physics department of biotechnology CHINA" } ], "family": "Miao", "given": "Lu", "sequence": "additional" }, { "affiliation": [ { "name": "Dalian Institute of Chemical Physics Department of Biotechnology Department of Biological Technology 457 Zhongshan Road 116023 Dalian CHINA" } ], "family": "Xu", "given": "Zhaochao", "sequence": "additional" } ], "container-title": "ChemBioChem", "container-title-short": "ChemBioChem", "content-domain": { "crossmark-restriction": true, "domain": [ "chemistry-europe.onlinelibrary.wiley.com" ] }, "created": { "date-parts": [ [ 2024, 6, 15 ] ], "date-time": "2024-06-15T03:10:25Z", "timestamp": 1718421025000 }, "deposited": { "date-parts": [ [ 2024, 6, 15 ] ], "date-time": "2024-06-15T03:10:27Z", "timestamp": 1718421027000 }, "indexed": { "date-parts": [ [ 2024, 6, 16 ] ], "date-time": "2024-06-16T00:19:30Z", "timestamp": 1718497170381 }, "is-referenced-by-count": 0, "issued": { "date-parts": [ [ 2024, 6, 14 ] ] }, "language": "en", "license": [ { "URL": "http://onlinelibrary.wiley.com/termsAndConditions#vor", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2024, 6, 14 ] ], "date-time": "2024-06-14T00:00:00Z", "timestamp": 1718323200000 } } ], "member": "311", "original-title": [], "prefix": "10.1002", "published": { "date-parts": [ [ 2024, 6, 14 ] ] }, "published-online": { "date-parts": [ [ 2024, 6, 14 ] ] }, "publisher": "Wiley", "reference-count": 0, "references-count": 0, "relation": {}, "resource": { "primary": { "URL": "https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cbic.202400404" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "Super‐resolution imaging reveals the mechanism of endosomal acidification inhibitors against SARS‐CoV‐2 infection", "type": "journal-article", "update-policy": "http://dx.doi.org/10.1002/crossmark_policy" }
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