The COVID-19 pandemic highlighted the critical need for efficient drug screening methods against live pathogenic viruses requiring high biosafety levels (BSL-3). Ongoing threats like avian influenza, Monkeypox, and Nipah viruses underscore the importance of pandemic preparedness through versatile screening tools. Current FDA-approved COVID-19 treatments (Remdesivir, Paxlovid, Molnupiravir) have limitations, emphasizing the urgent need for safer and more effective therapeutics. David Perlin’s group at Hackensack Meridian Health Center for Discovery and Innovation developed a rapid, semi-automated drug screening platform using a nano-luciferase reporter SARS-CoV-2 virus and a highly permissive A549 cell line that enables accelerated low-, mid-, and high-throughput screening. The platform was validated and shown to provide a robust luminescence signal that correlates with immunofluorescence assays and can be used to screen compounds against SARS-CoV-2. The platform was used to screen a 240-compound library, identifying 48 hits that inhibited more than 50% of viral growth, with 3 of the most potent and least toxic compounds being previously unreported as antivirals. The speed, efficiency, scalability, and robustness of the method make it a valuable tool for rapidly identifying potential therapeutics. The successful screening of the 240-compound library and identifying novel hits underscore the platform's utility. While certain limitations exist, the adaptability of this platform to other viruses positions it as a crucial asset for future pandemic preparedness efforts.
Madani A, Alvarez N, Park S, Murugan M, Perlin DS. Rapid luminescence-based screening method for SARS- CoV-2 inhibitors discovery. SLAS Discov. 2025 Mar;31:100211. doi: 10.1016/j.slasd.2025.100211. Epub 2025 Jan 15. PMID: 39824441.
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