Inhibitors of endosomal acidification suppress SARS-CoV-2 replication and relieve viral pneumonia in hACE2 transgenic mice

{ 'indexed': {'date-parts': [[2023, 6, 5]], 'date-time': '2023-06-05T18:29:44Z', 'timestamp': 1685989784052}, 'reference-count': 25, 'publisher': 'Springer Science and Business Media LLC', 'issue': '1', 'license': [ { 'start': { 'date-parts': [[2021, 2, 27]], 'date-time': '2021-02-27T00:00:00Z', 'timestamp': 1614384000000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'http://creativecommons.org/licenses/by/4.0/'}, { 'start': { 'date-parts': [[2021, 2, 27]], 'date-time': '2021-02-27T00:00:00Z', 'timestamp': 1614384000000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'http://creativecommons.org/licenses/by/4.0/'}], 'funder': [ { 'name': 'the New coronavirus pneumonia (NCP) epidemic prevention and control emergency ' 'scientific research project in Changchun City', 'award': ['Grant no. 20YF003']}, { 'name': 'the Key projects of science and technology boosting economy in 2020', 'award': ['Grant no. SQ2020YFF0417940']}], 'content-domain': {'domain': ['link.springer.com'], 'crossmark-restriction': False}, 'published-print': {'date-parts': [[2021, 12]]}, 'abstract': '<jats:title>Abstract</jats:title><jats:sec>\n' ' <jats:title>Background</jats:title>\n' ' <jats:p>Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2 and broke ' 'out as a global pandemic in late 2019. The acidic pH environment of endosomes is believed to ' 'be essential for SARS-CoV-2 to be able to enter cells and begin replication. However, the ' 'clinical use of endosomal acidification inhibitors, typically chloroquine, has been ' 'controversial with this respect.</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Methods</jats:title>\n' ' <jats:p>In this study, RT-qPCR method was used to detect the SARS-CoV-2N gene ' 'to evaluate viral replication. The CCK-8 assay was also used to evaluate the cytotoxic effect ' 'of SARS-CoV-2. In situ hybridization was used to examine the distribution of the SARS-CoV-2 ' 'gene in lung tissues. Hematoxylin and eosin staining was also used to evaluate ' 'virus-associated pathological changes in lung tissues.</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Results</jats:title>\n' ' <jats:p>In this study, analysis showed that endosomal acidification ' 'inhibitors, including chloroquine, bafilomycin A1 and NH<jats:sub>4</jats:sub>CL, ' 'significantly reduced the viral yields of SARS-CoV-2 in Vero E6, Huh-7 and 293T-ACE2 cells. ' 'Chloroquine and bafilomycin A1 also improved the viability and proliferation of Vero E6 cells ' 'after SARS-CoV-2 infection. Moreover, in the hACE2 transgenic mice model of SARS-CoV-2 ' 'infection, chloroquine and bafilomycin A1 reduced viral replication in lung tissues and ' 'alleviated viral pneumonia with reduced inflammatory exudation and infiltration in ' 'peribronchiolar and perivascular tissues, as well as improved structures of alveolar septum ' 'and pulmonary alveoli.</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Conclusions</jats:title>\n' ' <jats:p>Our research investigated the antiviral effects of endosomal ' 'acidification inhibitors against SARS-CoV-2 in several infection models and provides an ' 'experimental basis for further mechanistic studies and drug development.</jats:p>\n' ' </jats:sec>', 'DOI': '10.1186/s12985-021-01515-1', 'type': 'journal-article', 'created': {'date-parts': [[2021, 2, 27]], 'date-time': '2021-02-27T18:24:39Z', 'timestamp': 1614450279000}, 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 33, 'title': 'Inhibitors of endosomal acidification suppress SARS-CoV-2 replication and relieve viral ' 'pneumonia in hACE2 transgenic mice', 'prefix': '10.1186', 'volume': '18', 'author': [ {'given': 'Chao', 'family': 'Shang', 'sequence': 'first', 'affiliation': []}, {'given': 'Xinyu', 'family': 'Zhuang', 'sequence': 'additional', 'affiliation': []}, {'given': 'He', 'family': 'Zhang', 'sequence': 'additional', 'affiliation': []}, {'given': 'Yiquan', 'family': 'Li', 'sequence': 'additional', 'affiliation': []}, {'given': 'Yilong', 'family': 'Zhu', 'sequence': 'additional', 'affiliation': []}, {'given': 'Jing', 'family': 'Lu', 'sequence': 'additional', 'affiliation': []}, {'given': 'Chenchen', 'family': 'Ge', 'sequence': 'additional', 'affiliation': []}, {'given': 'Jianan', 'family': 'Cong', 'sequence': 'additional', 'affiliation': []}, {'given': 'Tingyu', 'family': 'Li', 'sequence': 'additional', 'affiliation': []}, {'given': 'Mingyao', 'family': 'Tian', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ningyi', 'family': 'Jin', 'sequence': 'additional', 'affiliation': []}, {'given': 'Xiao', 'family': 'Li', 'sequence': 'additional', 'affiliation': []}], 'member': '297', 'published-online': {'date-parts': [[2021, 2, 27]]}, 'reference': [ { 'key': '1515_CR1', 'doi-asserted-by': 'crossref', 'unstructured': 'Zhu N, Zhang D, Wang W, Li X, Tan W. 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The studies involving human participants were ' 'reviewed and approved by the Ethics Committee of the Chinese Academy of ' 'Military Medical Science (AMMS).', 'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Ethics approval and consent to participate'}}, { 'value': 'Not applicable.', 'order': 2, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Consent for publication'}}, { 'value': 'The authors declare no competing interests.', 'order': 3, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}], 'article-number': '46'}