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Updated: Sep 3, 2025
In Vitro Selection of Aptamers to Differentiate Infectious from Non-Infectious Viruses
Published on: September 7, 2022
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.
Abstract:
The Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the biggest public health challenge the world has witnessed in the past decades. SARS-CoV-2 undergoes constant mutations and new variants of concerns (VOCs) with altered transmissibility, virulence, and/or susceptibility to vaccines and therapeutics continue to emerge. Detailed analysis of host factors involved in virus replication may help to identify novel treatment targets. In this study, we dissected the metabolome derived from COVID-19 patients to identify key host factors that are required for efficient SARS-CoV-2 replication. Through a series of metabolomic analyses, in vitro, and in vivo investigations, we identified ATP citrate lyase (ACLY) as a novel host factor required for efficient replication of SARS-CoV-2 wild-type and variants, including Omicron. ACLY should be further explored as a novel intervention target for COVID-19.
Insights
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.
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.
