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Updated: Jun 27, 2026
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Procedures for the Identification of SARS-CoV-2 Entry Inhibitors as Potential Antivirals using MLV-Based Pseudoviruses
Published on: February 27, 2026
Targeting SARS-CoV-2 Structural and Accessory Proteins: Emerging Opportunities for Small-Molecule Coronavirus
Exequiel O J Porta1, Dana F AlKharboush1,2, Lauren Jackson1
1UCL School of Pharmacy, University College London, London WC1N 1AX, UK.
Pharmaceutics
|June 26, 2026
Summary
Structural and accessory proteins of SARS-CoV-2 present new antiviral targets. Targeting these proteins, like M, E, N, and ORF3a, offers complementary strategies to combat SARS-CoV-2, enhancing pandemic preparedness.
Area of Science:
- Virology
- Drug Discovery
- Structural Biology
Background:
- Antiviral development for SARS-CoV-2 has primarily focused on replication inhibitors.
- Structural and accessory proteins regulate critical viral functions beyond replication, presenting alternative therapeutic targets.
Purpose of the Study:
- To critically evaluate the small-molecule tractability of SARS-CoV-2 structural and accessory proteins.
- To identify promising non-canonical targets for antiviral drug development.
Main Methods:
- Comprehensive review of the SARS-CoV-2 structural and accessory proteomes.
- Focus on small-molecule tractability, translational relevance, and druggability.
- Assessment of structural accessibility, assay systems, and in vivo activity.
Main Results:
- The membrane (M), envelope (E), and nucleocapsid (N) proteins, along with ORF3a, show high potential for direct-acting small-molecule intervention.
- Spike (S) and host-interacting accessory proteins (ORF6, ORF8, ORF9b, ORF10) represent earlier-stage targets requiring further validation.
Conclusions:
- Targeting structural and accessory proteins offers a complementary approach to replication-directed antivirals for SARS-CoV-2.
- These non-canonical targets can enhance antiviral strategies, improve robustness, and bolster pandemic preparedness.
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