Lame 2-pp "prefusion" stabilization (i.e., inserting two consecutive prolines in hinge region of S2) is not going to disrupt the heparin sulfate binding capacity of the vaccine spike constructs owing to the fact NTD, RBD, FCS and R815 S2 are all documented sites of interaction
This diagram shows the heparin sulfate binding sites in the non-NTD regions of the spike (shown in blue).
See highlighted text below indicating that heparin sulfates are able to bind to both open and closed states of the spike.
As for the NTD heparin sulfate binding site (Residues 245 to 246), here's a good citation
As it relates to the "updated" spike vaccine constructs they're planning, let's not forget that the variant spike mutations in all regions are evolving toward more positive overall charge in certain critical areas to enhance interaction w heparin sulfate
Shit show folks!

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More from @Undergroundcou1

14 Jan
Another study looking at cross-neutralization activity of serum collected from individuals w a known variant. This group also created an antigenic map to look at relationship of antigens (viruses) and sera.…
Again, another disappointing study that didn't look at neutralization capacity of omicron serum vs itself and all other variants. Interesting that infection w ancestral variant yields productive neutralization ability against most all yet still most signif reduction vs omicron Image
Here's the antigenic map ImageImage
Read 7 tweets
14 Jan
Substantial heterogeneity in the magnitude and breadth of responses after infection and mRNA vaccination and may support the addition of more conserved viral antigens to existing SARS-CoV-2 vaccines.…
Neutralizing capacity of convalescent serum collected from mild/moderate cases not very robust or durable especially to omicron Image
This was collected from ppl naturally infected early in the pandemic. I'd like to see robustness and durability of plasma collected from those infected w delta or omicron. I'd also love love love to see data from ppl 2x reinfected
Read 5 tweets
13 Jan
Again, the PRRARS FCS site in the WT spike protein is an entirely logical and reasonable one to insert into a spike protein from an engineering point of view. The known canonical sequence is R-X-[KR]-R↓.
MERS FCS has the PR start and RSV stop as bookends just like SARSCOV2. Image
While RmYN02 has the NSP start and ARXV as bookends Image
Read 11 tweets
13 Jan
Really important paper here, first ones to look at concentration dependence of ACE2, TMPRSS2 and Furin on fusogenic capacity of omicron spike…
They see increased affinity of omicron spike for ACE2 but decreased fusogenicity vs other variants. They also confirm decreased proteolytic processing by furin.
But under certain optimal circumstances omicron may in fact be as or more fusogenic (eg. High ACE2 [ppl w hypertension] and high furin/TMPRSS2) Image
Read 13 tweets
12 Jan
So much to say about this paper, but you need to read it yourself. Outcomes and demographics of lab-confirmed infections across 4 successive sarscov2 waves in South Africa…
South Africa had previously experienced three COVID-19 waves related to different SARS- CoV-2 variants (ancestral strain, Beta and Delta respectively), each more clinically severe than the previous one with substantial mortality Image
Prior waves resulted in extremely high seroprevalence of 70% due to natural immunity/exposure. Impt to consider the high seroprevalence w moderate vaccination coverage in SA (39% and 46% of adults fully vaccinated in SA and the Western Cape respectively by end December 2021)
Read 8 tweets
12 Jan
If omicron is unable to be as efficiently cleaved by furin/TMRPSS2 and replicates less efficiently in lung cells (due to less cell-cell fusion) then it's not going to cause uncontrolled complement activation and/or severe ARDS at the level of the lungs.
It also should be more susceptible to antibody-driven immunity (because little/no cell-cell fusion) and perturbation via endosomal trafficking/acidification drugs
Also, heparin may be a much more effective treatment in omicron infected individuals.
Read 4 tweets

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