Lab chasing low hanging pebbles & shiny fruit #coronavirus #SARSCoV2 #SARS #COVID19 "We all work on COVID, I'm not special" *tweets are our own
Mar 12 • 7 tweets • 2 min read
A new preprint from our group about the importance of the SARS-CoV-2 spike furin cleavage site (FCS) for pathogenesis and possibly transmission.
tinyurl.com/2dya48ky
The SARS2 spike has 2 unusual features, the FCS in the S1/S2 loop & the extension of this loop (17AA vs 13AA in other sarbeCoVs). Our prior work showed deleting the FCS attenuated infection & pathogenesis by altering spike processing.
A thread (1/N)
While numerous studies have examined Omicron mutations, the major focus has been changes in the RBD that impact neutralization and confer immune escape.
Our interest in spike processing led us to the mutations adjacent to the furin cleavage site: H655Y, N679K, & P681H.
If you are at #KSRNAVirus22 you can talk to 1st author Bryan Johnson about it (probably wearing boots & maybe shorts).
A thread on the paper:
Bryan noticed several mutations in N at pos 203-204, notably a RG->KR found in alpha and omicron & R->M in delta.
The KR mutant in WA1 augmented replication in respiratory cells and disease in vivo.
R203M mutant had similar in vitro phenotype.
Dec 17, 2021 • 7 tweets • 4 min read
The furin cleavage site (FCS) has been linked to a nefarious origin for #SARSCoV2
Yet, our new manuscript shows the FCS alone is not sufficient to drive infection & pathogenesis.
Upstream QTQTN motif plays a critical role in SARS-CoV-2 virulence
a🧵
bit.ly/3q9cebx
An issue with #SARSCoV2 has been deletion of the FCS in stock titers. However, more common is deletion of the QTQTN motif upstream of the FCS.
Every variant we have generated has had this deletion varying from 10-100%.
We generated a dQTQTN mutant in WA1 to explore its role
Aug 19, 2021 • 12 tweets • 3 min read
After an hour of looking, have not found convincing data that booster are needed for the majority.
My worry, is that even with a booster, breakthrough will still happen, especially with #DeltaVariant .
Some musings on the need for #COVID19 vaccine boosters
1st, the data for for immune compromised patients is convincing. A third dose drives up the serum neutralizing antibody levels with most having very low to non detectable levels of protection after 2 doses.
Data not perfect, but is consistent and clear that a third dose helps.
Jul 26, 2021 • 9 tweets • 3 min read
Been getting lots of questions about the #COVID19 delta variant.
While the epi data makes it clear that this variant is more transmissible, the biology is a bit different than the other VOCs.
A thread of musings about delta and why there is concern (1/9)
Like the other alpha, beta, & gamma #COVID19 variants, most focus has been on mutations in the spike protein for delta.
While there are many additional backbone mutations, none have been clearly indicated to drive emergence of delta.
Still not enough known though. (2/9)
Jan 25, 2021 • 6 tweets • 4 min read
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
The proponents are not wrong. Herd immunity is the only way #COVID19 ends. Until then, this nightmare will continue.
Question comes down to exposure, multiplication, and what's acceptable.
There are 2 ways to herd immunity:
1) People get infected and survive 2) People get a working vaccine that induces immunity and are protected
That's pretty much it.
The herd immunity strategy says we're all getting it anyway & we should cause the vaccine takes too long.
Apr 12, 2020 • 7 tweets • 3 min read
Gotten questions about reactivation/reinfection with #SARSCoV2 & wanted to see some data
But since data isn't a requirement these days for #COVID19 speculation, I'll offer:
I doubt this is some kind of herpes virus like latency/reactivation
RNA positive PCR is not live virus
So what is happening? Here are possibilities
1) These people hadn't cleared the virus in the 1st place
2) The viral RNA remains in debris/damage after virus is cleared & pushes + test as it is repaired
3) #SARSCov2 evolved a complex latency/reactivation mechanism
Apr 5, 2020 • 19 tweets • 6 min read
Let’s talk immunity to #COVID19. I am on record saying immunity may only last 1-2 years based on serum neutralizing antibody (Ab) to MERS and common cold CoVs.
Does this mean we could go through this again in a few years? That I am less sure of.
First, while #SARS2 is a particularly successful pathogen, our immune system is fully capable of control.
The vast majority of people will survive because their innate immune system will limit initial damage and their adaptive immune system will provide sterilizing immunity.
There are many more cases than confirmed to this point and the low overall mortality rate is good...
but, both SARS/MERS have a long period between onset and median day of death (~12 days). Damage to lung is what kills and can take time
Keeping an eye on severe cases (13%). If they require ventilators, these are people likely to succumb. Even with numbers skewed toward severe cases, this is worrisome.
Even if these people survive, they may never regain lung function/capacity. Their lives won't be the same
Jan 21, 2020 • 5 tweets • 2 min read
So I'd be cautious with this interpretation. The paper (bit.ly/2vd7mJV) models the structural interactions between the spike of #nCoV2019 & human ACE2, the receptor for SARS. They conclude that it is likely the new virus can use hACE2. They haven't yet proven it, yet.
In our own structural modeling, we came to a similar conclusion. While not proven, hACE2 is the betting favorite for #nCoV2019 receptor.
Yeah, not good, especially considering the history of SARS-CoV.
The silver lining: the quality and location of ACE2 binding matters.
Jan 1, 2020 • 16 tweets • 5 min read
Been doing my best to avoid twittering over the break, but a rumored return of #SARS in 2020 caused me to dive into twitter and google translate for more information. Here are some random facts, thoughts, and speculation on what may or may not be happening with in Wuhan.
First, #SARS does not necessarily mean SARS-CoV, the virus that caused the 2002-03 worldwide outbreak. Instead, it could refer to many illnesses like bird flu bacterial pneumonias as in the past before id. However, the description of atypical viral pneumonia echoes of SARS-CoV.
