An ACAT inhibitor suppresses SARS-CoV-2 replication and boosts antiviral T cell activity

• DOI: 10.1371/journal.ppat.1011323
• Publication Date: 2023-05-03T17:40:26Z
• Authors: Peter A. C. Wing; Nathalie M. Schmidt; Rory Peters; Maximilian Erdmann; Rachel Brown; Hao Wang; Leo Swadling; ; Joseph Newman; Nazia Thakur; Kaho Shionoya; Sophie B. Morgan; Timothy SC Hinks; Koichi Watashi; Dalan Bailey; Scott B. Hansen; Andrew D. Davidson; Mala K. Maini; Jane A. McKeating
• Keywords: Lipid raft

The severity of disease following infection with SARS-CoV-2 is determined by viral replication kinetics and host immunity, early T cell responses and/or suppression viraemia driving a favourable outcome. Recent studies uncovered role for cholesterol metabolism in the life cycle function. Here we show that blockade enzyme Acyl-CoA:cholesterol acyltransferase (ACAT) Avasimibe inhibits pseudoparticle disrupts association ACE2 GM1 lipid rafts on membrane, perturbing attachment. Imaging RNAs at single level using replicon model identifies capacity to limit establishment complexes required RNA replication. Genetic transiently silence or overexpress ACAT isoforms confirmed infection. Furthermore, boosts expansion functional SARS-CoV-2-specific cells from blood patients sampled during acute phase Thus, re-purposing inhibitors provides compelling therapeutic strategy treatment COVID-19 achieve both antiviral immunomodulatory effects. Trial registration : NCT04318314 .