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An ACAT inhibitor regulates SARS-CoV-2 replication and antiviral T cell activity (preprint)
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-333065
ABSTRACT
The severity of disease following infection with SARS-CoV-2 is determined by viral replication kinetics and host immunity, with early T cell responses and/or suppression of viraemia driving a favourable outcome. Recent studies have uncovered a role for cholesterol metabolism in the SARS-CoV-2 life cycle and in T cell function. Here we show that blockade of the enzyme Acyl-CoAcholesterol acyltransferase (ACAT) with Avasimibe inhibits SARS-CoV-2 entry and fusion independent of transmembrane protease serine 2 expression in multiple cell types. We also demonstrate a role for ACAT in regulating SARS-CoV-2 RNA replication in primary bronchial epithelial cells. Furthermore, Avasimibe boosts the expansion of functional SARS-CoV-2-specific T cells from the blood of patients sampled in the acute phase of infection. Thus, re-purposing of available ACAT inhibitors provides a compelling therapeutic strategy for the treatment of COVID-19 to achieve both antiviral and immunomodulatory effects.

Full text: Available Collection: Preprints Database: EuropePMC Language: English Year: 2022 Document Type: Preprint

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Full text: Available Collection: Preprints Database: EuropePMC Language: English Year: 2022 Document Type: Preprint