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

Shang et al., Virology Journal, doi:10.1186/s12985-021-01515-1
Feb 2021  
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In Vitro study showing that endosomal acidification inhibitors including chloroquine reduce SARS-CoV-2 replication in Vero E6, Huh-7, and 293T-ACE2 cells.
Shang et al., 27 Feb 2021, peer-reviewed, 12 authors. Contact: (corresponding author),,
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
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Inhibitors of endosomal acidification suppress SARS-CoV-2 replication and relieve viral pneumonia in hACE2 transgenic mice
Chao Shang, Xinyu Zhuang, He Zhang, Yiquan Li, Yilong Zhu, Jing Lu, Chenchen Ge, Jianan Cong, Tingyu Li, Mingyao Tian, Ningyi Jin, Xiao Li
Virology Journal, doi:10.1186/s12985-021-01515-1
Background: 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. Methods: 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. Results: In this study, analysis showed that endosomal acidification inhibitors, including chloroquine, bafilomycin A1 and NH 4 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. Conclusions: 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.
Ethics approval and consent to participate The animal experimental protocols were approved by the Institutional Animal Care and Use Committee of the Academy of Military Medical Science (AMMS) and all efforts were made to minimize animal suffering and reduce the number of animals used for the experiments. The studies involving human participants were reviewed and approved by the Ethics Committee of the Chinese Academy of Military Medical Science (AMMS). Consent for publication Not applicable. Competing interests The authors declare no competing interests. • fast, convenient online submission • thorough peer review by experienced researchers in your field • rapid publication on acceptance • support for research data, including large and complex data types • gold Open Access which fosters wider collaboration and increased citations maximum visibility for your research: over 100M website views per year • At BMC, research is always in progress. Learn more Ready to submit your research Ready to submit your research ? Choose BMC and benefit from: ? Choose BMC and benefit from: Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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