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[Preprint]. 2022 Dec 20:2022.12.19.521044. [Version 1] doi: 10.1101/2022.12.19.521044

An approach to rapid distributed manufacturing of broad spectrum anti-viral griffithsin using cell-free systems to mitigate pandemics

Shayan G Borhani, Max Z Levine, Lauren H Krumpe, Jennifer Wilson, Curtis J Henrich, Barry R O’Keefe, Donald Lo, G Sitta Sittampalam, Alexander G Godfrey, R Dwayne Lunsford, Venkata Mangalampalli, Dingyin Tao, Christopher A LeClair, Aaron Thole, Douglas Frey, James Swartz, Govind Rao
PMCID: PMC9810220  PMID: 36597541

Abstract

This study describes the cell-free biomanufacturing of a broad-spectrum antiviral protein, griffithsin (GRFT) such that it can be produced with consistent purity and potency in less than 24 hours. We demonstrate GRFT production using two independent cell-free systems, one plant and one microbial. Griffithsin purity and quality were verified using standard regulatory metrics. Efficacy was demonstrated in vitro against SARS-CoV-2 and HIV-1 and was nearly identical to that of GRFT expressed in vivo . The proposed production process is efficient and can be readily scaled up and deployed anywhere in the world where a viral pathogen might emerge. The current emergence of viral variants has resulted in frequent updating of existing vaccines and loss of efficacy for front-line monoclonal antibody therapies. Proteins such as GRFT with its efficacious and broad virus neutralizing capability provide a compelling pandemic mitigation strategy to promptly suppress viral emergence at the source of an outbreak.

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