Our study examining a furin-cleavage site deletion mutant in #COVID19 is now out @Nature

With a short thread (cause who has time to read beyond twitter) (1/6 https://go.nature.com/2MnGlfq 

First, thanks to our collaborations with @utmbhealth @WUSTLmed @ihii_utmb @bmb_utmb @SutharLab @UTMB_WRCEVA @DanieleSwetnam @AndrewRouth @KariDebbink @scottweaverutmb @VirusWhisperer @aguilar_pv and others.

Lots of effort from lots of people
2/6

- The furin cleavage site (FCS) is needed for replication in respiratory cells (Calu3) & for pathogenesis in mice & hamsters in #COVID19

- Loss of FCS shifts neutralization profiles to convalescent sera making the mutant virus less susceptible

3/6

- FCS loss has major advantage in VeroE6 cells vs WT & is a risk for tissue culture adaptation. FCS mutation occurring not question of if, but when

- Advantage diminished (but not lost) on VeroE6 expressing TMPRSS2. Based on spike processing, virions similar from these cell

4/6

-Loss of FCS changes virion clustering (based on EM) with deletion virus clumping in groups of >3 virions. Also alters the particle/PFU.

- FCS mutant protects from WT SARS-CoV-2 rechallenge and has potential as part of vaccine platform

5/6

As new variant work heats up, the status of FCS must be considered as it impacts infection, pathogenesis, and neutralization.

With each passage, the risk of FCS deletion increases.

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