Exocyst Complex Component 2 (EXOC2) Is An Important Host Factor In SARS-CoV-2 Infections


Researchers from Kyoto University – Japan and AMED-CREST, Japan Agency for Medical Research and Development (AMED)- Japan have in a news study found that Exocyst Complex Component 2 (EXOC2) is an important host factor in SARS-CoV-2 infections.

The study findings were published in the peer reviewed journal: iScience.

Here we demonstrated that EXOC2 is necessary for SARS-CoV-2 infection.

CRISPRi-based and siRNA-based EXOC2 knockdown decreased the infection efficiency of SARS-CoV-2 in human iPS cells and AO, respectively.

EXOC2 knockdown also increased the expression level of IFNW1, which has antiviral effects against SARS-CoV-2 and is one of the reasons for the antiviral effect mediated by EXOC2 knockdown.

We also found that the F-actin inhibitor Cytochalasin D significantly decreased the SARS-CoV-2 infection efficiency. These findings highlight that EXOC2 is a potential target for clinical therapeutics; especially, pharmacological EXOC2 inhibitors may prevent or reduce the impact of SARS-CoV-2 infection.

EXOC2/Sec5 is one of the subunits of the exocyst complex. It is also known as an effector for small GTPases in the Ras subfamily, RalA and RalB, which are involved in multiple cellular events, such as cell polarization, migration, apoptosis, cytokinesis, autophagy, host defense, tumorigenesis, and metastasis 26,31,32.

However, it is still not clear whether the exocyst complex or other exocyst subunits are necessary for cellular homeostasis. Because cell viability was slightly reduced by EXOC2 knockdown, it is necessary to carefully consider toxicity of this knockdown when conducting drug discovery focusing on EXOC2.

Tunneling nanotubes (TNTs), which are different from other known protrusions (filopodia, microvilli, and dendritic spines), are mainly composed of F-actin and regulated by EXOC2/Sec5 28. TNTs have been found particularly in immune cells and neurons cell lines 33,34 and were proven to associate with many pathogens, especially viruses, such as HIV, herpesviruses, and influenza A.

Importantly, viruses can hijack TNTs to facilitate viral entry, virus trafficking, cell-to-cell spread, and their protection from immune surveillance 35,36.

However, the signaling pathways that control TNT formation seem context-dependence, and several EXOC2-independent pathways, such as the Rab35-ACAP2-ARF6-EHD1 cascade in neuron cells 37 and the MAPK pathway in squamous cancer cells 38, have been reported to control TNT formation. Hence, the potency of drugs targeting TNTs should be investigated in other somatic cells.


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