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Updated: Aug 16, 2026
11:43
Procedures for the Identification of SARS-CoV-2 Entry Inhibitors as Potential Antivirals using MLV-Based Pseudoviruses
Published on: February 27, 2026
Targeting host lipogenesis with a diarylamide inhibitor disrupts SARS-CoV-2 replication
Xintian Zhang1, Tingfu Du1, Yongjian Wang2
1State Key Laboratory of Respiratory Health and Multimorbidity, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, China.
Iscience
|August 15, 2026
Summary
A new molecule, compound 10, effectively inhibits SARS-CoV-2 by targeting host lipogenesis. This host-directed strategy shows promise for developing new antiviral therapies against resistant viruses.
Area of Science:
- Virology
- Molecular Biology
- Drug Discovery
Background:
- Direct-acting antivirals face resistance challenges.
- Host-directed strategies offer an alternative by targeting conserved cellular pathways.
- Identifying novel host-directed antiviral compounds is crucial.
Purpose of the Study:
- To identify and characterize a novel diarylamide molecule, compound 10, as a potential host-directed antiviral agent against SARS-CoV-2.
- To elucidate the mechanism of action of compound 10.
- To evaluate the in vivo efficacy of compound 10.
Main Methods:
- Synthesis and in vitro testing of compound 10.
- Mechanistic studies involving lipogenesis markers (FASN, SCD1) and fatty acid supplementation.
- Assessment of nuclear receptor coactivator 1 (NCOA1/SRC-1) binding and degradation.
- In vivo efficacy studies in SARS-CoV-2-infected hamsters via intranasal administration.
Main Results:
- Compound 10 demonstrated potent inhibition of SARS-CoV-2, exceeding that of clofoctol.
- It suppressed host lipogenesis by downregulating FASN and SCD1.
- Compound 10 promoted NCOA1/SRC-1 degradation, inhibiting lipogenic enzyme transcription.
- Intranasal administration of compound 10 reduced viral loads and lung pathology in hamsters.
Conclusions:
- Compound 10 is a promising antiviral candidate targeting SARS-CoV-2 replication through host lipogenesis.
- It disrupts viral replication by modulating host cellular pathways.
- Compound 10 provides a novel chemotype for developing host-directed antiviral therapies.
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