We've created an interactive website to visualize >100,000 experimental measurements of how mutations to #SARSCoV2 RBD affect binding by antibodies & sera: jbloomlab.github.io/SARS2_RBD_Ab_e… Explore it to examine a wealth of information about the antigenic effects of viral mutations. (1/n)
Over the last 9 months, the indefatigable @tylernstarr & @AllieGreaney have used deep mutational scanning to measure how the 2,304 RBD mutations tolerated for protein folding / ACE2 binding affect recognition by 50 antibodies / sera. Data scattered across multiple papers. (2/n)
We have consolidated these data so they can be explored to understand antigenic impacts of mutations observed during genomic surveillance. Best way to look at data is to explore the website at jbloomlab.github.io/SARS2_RBD_Ab_e…, but here are some static-image summaries: (3/n)
First, we used experimental measurements to organize antibodies in the space of "viral escape." This organization mostly concordant with structural classification scheme of @cobarnes27@bjorkmanlab; you can click on specific antibody to see its sites of escape mutations. (4/n)
For any subset of antibodies, you can visualize mean antigenic effect of mutations at each RBD site. It's striking how peaks in this plot include so many sites of emerging mutations: E484, L452, K417, R346, etc. (5/n)
You can also zoom in on sites of interest to see which antibodies/sera are affected by mutations there. For instance, @Tuliodna recently reported a new lineage with a mutation at R346: mutations there impact several class 3 antibodies such as C135. (6/n)
You can also select specific antibodies to see their binding escape mutations. For instance, LY-CoV555 (bamlanivimab) is unfortunately affected by mutations at E484 and L452, which is why US government recently halted distribution of this therapeutic antibody. (7/n)
You can also visualize sera binding-escape mutations. For instance, below shows mutations that reduce binding by convalescent sera from @HelenChuMD's HAARVI cohort are most similar to ones (eg, E484K) that affect class 2 antibodies. (8/n)
In new study led by @bblarsen1 in collab w @veeslerlab @VUMC_Vaccines we map functional & antigenic landscape of Nipah virus receptor binding protein (RBP)
Results elucidate constraints on RBP function & provide insight re protein’s evolutionary potentialbiorxiv.org/content/10.110…
Nipah is bat virus that sporadically infects humans w high (~70%) fatality rate. Has been limited human transmission
Like other paramyxoviruses, Nipah uses two proteins to enter cells: RBP binds receptor & then triggers fusion (F) protein by process that is not fully understood
RBP forms tetramer in which 4 constituent monomers (which are all identical in sequence) adopt 3 distinct conformations
RBP binds to two receptors, EFNB2 & EFNB3
RBP’s affinity for EFNB2 is very high (~0.1 nM, over an order of magnitude higher than SARSCoV2’s affinity for ACE2)
Over 4 yrs after being first to publicly release SARS-CoV-2 genome, Yong-Zhen Zhang just published large set of viral seqs from first stage of COVID-19 outbreak in China
Zhang recruited nearly all COVID-19 patients hospitalized at Shanghai Public Health Center in first 2/3 (Jan-Sep) of 2020.
The largest source of Shanghai patients in Jan/Feb 2020 was imported cases from Wuhan or elsewhere in Hubei, thereby providing window into Wuhan outbreak.
Overall, Zhang obtained 343 near-full-length SARS-CoV-2 sequences from 226 distinct patients, including 133 sequences from samples collected no later than Feb-15-2020.
A phylogenetic tree showing these sequences is below.
In new study led by Caleb Carr & @khdcrawford, we measure how all mutation to Lassa virus glycoprotein complex (GPC) affect cell entry & antibody escape
Results show how prospective assessment of effects of mutations can inform design of countermeasures biorxiv.org/content/10.110…
As background, Lassa virus causes of thousands of deaths each year, mostly from spillovers from its rodent host, but there is occasional human-to-human transmission.
Lassa is biosafety-level-4 priority pathogen, & efforts are underway to develop vaccines & antibody therapeutics.
We used pseudovirus deep mutational scanning to study effects of nearly all 9,820 amino-acid mutations to Lassa’s GPC at biosafety-level-2 by making genotype-phenotype linked libraries of lentiviral pseudotypes blog.addgene.org/viral-vectors-…
Here is my brief analysis of Dec-28-2019 SARSCoV2 submission to Genbank.
This analysis supports my conclusion to WSJ () that this submission does not tell origin of virus, but does show sequence known to Chinese Academy of Sciences weeks before released wsj.com/politics/natio…
Here is link to my full analysis:
See also images of the same posted below (although it's probably just easier to click on link above and read HTML). github.com/jbloom/SARS2_2…
I also don't think Genbank/NCBI could have reasonably known at time that this sequence was so valuable given that Chinese govt did not announce they had sequence or had submitted it, and Genbank receives vast numbers of submissions.
As background, human influenza constantly evolving. So people exposed to different strains, depending on their age & idiosyncratic history of infection/vaccination.
Different exposure histories cause people to make antibodies w different specificities