SARS-CoV-2 infects cells after viral entry via clathrin-mediated endocytosis

Bayati, Armin; Kumar, Rahul; Francis, Vincent; McPherson, Peter S.

doi:10.1016/j.jbc.2021.100306

Cited by 377 publications

(368 citation statements)

References 53 publications

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“…For instance, Ou et al identified the SAS-CoV-2 receptor, entry pathway and potential drug targets by using SARS-CoV-2 S protein pseudovirus system [ 52 ]. Bayati et al developed SARS-CoV-2 S protein pseudovirus to study the virus entry, which confirmed that SARS-CoV-2 used clathrin-mediated endocytosis to get into cells [ 53 ]. Besides, Wibmer et al employed pseudovirus model to evaluate the responses of therapeutically relevant antibodies to SARS-CoV-2 [ 54 ].…”

Section: Resultsmentioning

confidence: 98%

Macrophage biomimetic nanocarriers for anti-inflammation and targeted antiviral treatment in COVID-19

Tan

Meng

et al. 2021

J Nanobiotechnol

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Background The worldwide pandemic of COVID-19 remains a serious public health menace as the lack of efficacious treatments. Cytokine storm syndrome (CSS) characterized with elevated inflammation and multi-organs failure is closely correlated with the bad outcome of COVID-19. Hence, inhibit the process of CSS by controlling excessive inflammation is considered one of the most promising ways for COVID-19 treatment. Results Here, we developed a biomimetic nanocarrier based drug delivery system against COVID-19 via anti-inflammation and antiviral treatment simultaneously. Firstly, lopinavir (LPV) as model antiviral drug was loaded in the polymeric nanoparticles (PLGA-LPV NPs). Afterwards, macrophage membranes were coated on the PLGA-LPV NPs to constitute drugs loaded macrophage biomimetic nanocarriers (PLGA-LPV@M). In the study, PLGA-LPV@M could neutralize multiple proinflammatory cytokines and effectively suppress the activation of macrophages and neutrophils. Furthermore, the formation of NETs induced by COVID-19 patients serum could be reduced by PLGA-LPV@M as well. In a mouse model of coronavirus infection, PLGA-LPV@M exhibited significant targeted ability to inflammation sites, and superior therapeutic efficacy in inflammation alleviation and tissues viral loads reduction. Conclusion Collectively, such macrophage biomimetic nanocarriers based drug delivery system showed favorable anti-inflammation and targeted antiviral effects, which may possess a comprehensive therapeutic value in COVID-19 treatment.

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Section: Resultsmentioning

confidence: 98%

Macrophage biomimetic nanocarriers for anti-inflammation and targeted antiviral treatment in COVID-19

Tan

Meng

et al. 2021

J Nanobiotechnol

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“…Expression level of these proteases depends on cell type and hence their relative importance to support successful infection would hinge in part on their relative expression. Cathepsin is primarily found in late endosomes or lysosomes and requires low pH for optimal enzymatic activity; for these reasons it has been proposed that SARS-CoV-2 entry occurs from the endolysosomal compartment (32, 33). In contrast, TMPRSS2 is thought to be at the cell surface (34) and its optimal proteolytic activity is pH independent (35); hence it has been inferred that TMPRSS2 cleavage of spike S protein occurs on virions at the plasma membrane from which viral entry is then assumed to occur (1).…”

Section: Resultsmentioning

confidence: 99%

Synergistic block of SARS-CoV-2 infection by combined drug inhibition of the host entry factors PIKfyve kinase and TMPRSS2 protease

Kreutzberger

Sanyal

Ojha

et al. 2021

Preprint

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Repurposing FDA-approved inhibitors able to prevent infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could provide a rapid path to establish new therapeutic options to mitigate the effects of coronavirus disease 2019 (COVID-19). Proteolytic cleavages of the spike S protein of SARS-CoV-2, mediated by the host cell proteases cathepsin and TMPRSS2, alone or in combination, are key early activation steps required for efficient infection. The PIKfyve kinase inhibitor apilimod interferes with late endosomal viral traffic, and through an ill-defined mechanism prevents in vitro infection through late endosomes mediated by cathepsin. Similarly, inhibition of TMPRSS2 protease activity by camostat mesylate or nafamostat mesylate prevents infection mediated by the TMPRSS2-dependent and cathepsin-independent pathway. Here, we combined the use of apilimod with camostat mesylate or nafamostat mesylate and found an unexpected ~5-10 fold increase in their effectiveness to prevent SARS-CoV-2 infection in different cell types. Comparable synergism was observed using both, a chimeric vesicular stomatitis virus (VSV) containing S of SARS-CoV-2 (VSV-SARS-CoV-2) and SARS-CoV-2 virus. The substantial ~5 fold or more decrease of half maximal effective concentrations (EC50 values) suggests a plausible treatment strategy based on the combined use of these inhibitors.

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“…Here by using different chemical inhibitors and CRISPR/Cas9 targeting the major protein in clathrin coat formation, we demonstrated that SARS-CoV-2 entry also was dependent on clathrin. While we are preparing this manuscript, Bayati et al reported that the Spike protein of SARS-CoV-2 endocytosis is dependent on clathrin and S pseudovirus can be blocked by CHC siRNA treatment(42). Consistently, we also showed that SARS-CoV-2 pseudovirus enters cell via CME, in addition, we also showed that this process is independent of caveolae-mediated endocytosis, another common endocytosis pathway.…”

Section: Discussionmentioning

confidence: 99%

Cytoplasmic domain and enzymatic activity of ACE2 is not required for PI4KB dependent endocytosis entry of SARS-CoV-2 into host cells

Yang

Zhao

et al. 2021

Preprint

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The recent COVID-19 pandemic poses a global health emergency. Cellular entry of the causative agent SARS-CoV-2 is mediated by its spike protein interacting with cellular receptor- human angiotensin converting enzyme 2 (ACE2). Here, we used lentivirus based pseudotypes bearing spike protein to demonstrate that entry of SARS-CoV-2 into host cells is dependent on clathrin-mediated endocytosis, and phosphoinositides play essential role during this process. In addition, we showed that the intracellular domain and the catalytic activity of ACE2 is not required for efficient virus entry. These results provide new insights into SARS-CoV-2 cellular entry and present potential targets for drug development.

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SARS-CoV-2 infects cells after viral entry via clathrin-mediated endocytosis

Cited by 377 publications

References 53 publications

Macrophage biomimetic nanocarriers for anti-inflammation and targeted antiviral treatment in COVID-19

Macrophage biomimetic nanocarriers for anti-inflammation and targeted antiviral treatment in COVID-19

Synergistic block of SARS-CoV-2 infection by combined drug inhibition of the host entry factors PIKfyve kinase and TMPRSS2 protease

Cytoplasmic domain and enzymatic activity of ACE2 is not required for PI4KB dependent endocytosis entry of SARS-CoV-2 into host cells

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