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Targeting ACLY efficiently inhibits SARS-CoV-2 replication.

Terrence Tsz-Tai Yuen1, Jasper Fuk-Woo Chan1,2,3,4,5,6, Bingpeng Yan1

  • 1State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, and Carol Yu Centre for Infection, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.

International Journal of Biological Sciences
|July 25, 2022
PubMed
Summary

Researchers identified ATP citrate lyase (ACLY) as a crucial host factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication. Targeting ACLY may offer a new strategy against COVID-19 and its variants.

Keywords:
ACLYCOVID-19DeltaOmicronSARS-CoV-2metabolomics

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Area of Science:

  • Virology
  • Metabolomics
  • Drug Discovery

Background:

  • The COVID-19 pandemic, caused by SARS-CoV-2, presents ongoing global health challenges.
  • Emerging SARS-CoV-2 variants necessitate the identification of new therapeutic targets.
  • Understanding host-pathogen interactions is key to developing effective treatments.

Purpose of the Study:

  • To identify host factors essential for SARS-CoV-2 replication by analyzing patient metabolomes.
  • To investigate the role of identified host factors in the replication of SARS-CoV-2 and its variants.

Main Methods:

  • Metabolomic analysis of COVID-19 patient samples.
  • In vitro and in vivo experiments to validate host factor involvement.
  • Assessment of viral replication in the presence and absence of the target factor.

Main Results:

  • ATP citrate lyase (ACLY) was identified as a critical host factor for SARS-CoV-2 replication.
  • ACLY is required for the efficient replication of both wild-type SARS-CoV-2 and variants like Omicron.
  • Metabolomic dissection revealed ACLY's role in supporting viral replication.

Conclusions:

  • ATP citrate lyase (ACLY) is a novel host factor essential for SARS-CoV-2 replication.
  • ACLY represents a promising therapeutic target for developing new COVID-19 interventions.
  • Further research into ACLY inhibition could lead to effective treatments against current and future SARS-CoV-2 variants.