Vineet Menachery, Virtual COVID-19 Symposium: November 04, 2020

Vineet Menachery, PhD, Assistant Professor, Department of Microbiology & Immunology, University of Texas Medical Branch, "Deletion of the Furin Cleavage Site Attenuates SARS-CoV-2 Pathogenesis"

Dr. Menachery presents his work on SARS furin motif S1 cleavage site, and how it may provide insight to infection pathogenesis and neutralization. Dr. Menachery’s group created SARS-Cov2- Furin Mutant (dPRRA), which has a larger plaque size than WT. dPRRA also had faster replication in Vero cells, and lost the S1 furan cleavage site, showing that dPRRA has minimal spike processing compared to WT SARS-CoV. In Calu3 respiratory cells, dPRRA attenuated, and loss of furin site also changed SARS2 spike processing, but showed different spike processing in Vero versus Calu3. In addition, dPRRA competition assay showed that dPRRA mutant dominates in Vero cells; yet, the addition of TMPRSS2 expression removes dPRRA advantage. These findings showed that efforts must be made to limit selection of dPRRA mutations.
In vivo studies were also conducted, which showed that dPRRA causes attenuated disease in hamsters, and protects them from WT challenge. Mouse model studies showed that dPRRA mutant attenuates in early lung replication and overall disease and damage. Dr. Menachery further discussed neutralization studies, and presented that dPRRA mutant virus is more resistant to neutralization than WT.

Видео Vineet Menachery, Virtual COVID-19 Symposium: November 04, 2020 канала Herbert Irving Comprehensive Cancer Center at Columbia