XBB.1.16.21 sublineage with ORF1a:G963D first detected in Utrecht, Netherlands (73 GISAID seqs as of 2023-09-23; UK, Switzerland, USA, Canada, Belgium, Netherlands, Italy, Germany, Ireland, Portugal)

[alurqu]

There may be a XBB.1.16.21 sublineage with ORF1a:G963D (G3153A; NSP3:G145D) first detected in Utrecht, Netherlands.

As of 2023-08-25, Cov-Spectrum reports 23 good-quality (24 total) XBB.1.16.21+ORF1a:963D sequences. Source: https://cov-spectrum.org/explore/World/AllSamples/AllTimes/variants?variantQuery=nextcladePangoLineage%3AXBB.1.16.21+%26+ORF1a%3AG963D&nextcladeQcOverallScoreTo=29&

This one may or may not grow significantly. XBB.1.16.21 is a relatively slow sublineage of XBB.1.16. And ORF1a:G963D is inconsistent between clades on whether it helps or hurts viral fitness (see Bloom and Neher fitness estimates by clade below. However, this lineage has grown by 33% from 24 to 32 in GISAID in the August 23, 24, and 25 submissions, and this lineage has been detected in 7 countries on two continents, so it may indeed have significant growth capability.

As of 2023-08-25, UShER shows all of the CoV-Spectrum samples are on a single subtree with evidence of additional branching: To visualize on UShER: https://nextstrain.org/fetch/github.com/alurqu/pango-designation-support-alurqu/raw/main/2023/08/subtreeAuspice1_genome_CoV-Spectrum_XBB.1.16.21%2BORF1a_963D.json?c=gt-ORF1ab_963&label=id%3Anode_6823993

GISAID query: Spike_E180V, Spike_T478R, Spike_F486P, NSP6_L260F, NSP14_D222Y, NSP8_V130I, NSP3_G145D

First GISAID sequence: Utrecht, Netherlands 2023-07-14

Most Recent GISAID sequence: Ontario, Canada 2023-08-16

A zip archive of GenBank-formatted and derived metadata and FASTA files plus CoV-Spectrum-derived UShER output files for these sequences is available at Support-XBB.1.16.21+ORF1a_963D.zip

A CoV-Spectrum list of GISAID EPI ISLs for good-quality sequences is available at gisaid-epi-isl+XBB.1.16.21+ORF1a_963D.txt

Potential effects of the non-synonymous mutation on viral relative fitness

Now to consider the clade-specific Bloom and Neher estimates (from https://github.com/jbloomlab/SARS2-mut-fitness/blob/main/results/aa_fitness/aamut_fitness_by_clade.csv) of the fitness effects of the non-synonymous mutations in their order on the UShER tree:

For ORF1a:G963D,

clade,gene,aa_mutation,delta_fitness 20A,ORF1ab,G963D,-0.84518 20B,ORF1ab,G963D,0.21044 20C,ORF1ab,G963D,-0.40835 20E,ORF1ab,G963D,-1.4323 20G,ORF1ab,G963D,-1.8166 20I,ORF1ab,G963D,0.19531 21C,ORF1ab,G963D,0.4628 21I,ORF1ab,G963D,-0.37634 21J,ORF1ab,G963D,-0.040515 21K,ORF1ab,G963D,0.29048 21L,ORF1ab,G963D,0.64288 22A,ORF1ab,G963D,0.51572 22B,ORF1ab,G963D,0.50179 22C,ORF1ab,G963D,0.47454 22D,ORF1ab,G963D,0.30342 22E,ORF1ab,G963D,0.89183 22F,ORF1ab,G963D,-0.30134 23A,ORF1ab,G963D,0.11896

ORF1a:G963D appears to be associated with a significant sign epistatis effect (reference Nielsen et al, “Host heterogeneity and epistasis explain punctuated evolution of SARS-CoV-2”, PLOS Computational Biology, https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1010896) between clades with Bloom and Neher delta_fitness values ranging from a negative -1.82 in clade 20G to a fairly positive +0.89 in clade 22E. The closer clades to this lineage for which estimates are available, 22F and 23A, show mixed but weak effects for this mutation. It is possible although definitely uncertain that ORF1a:G963D might be associated with a viral fitness advantage in XBB.1.16's clade 22B. So for this lineage, the Bloom and Neher analysis is inconclusive with the available data.

[alurqu]

This may be fizzling out. If it doesn't grow more soon then closure as not planned may be merited.

[FedeGueli]

73 now but only 4 samples in September i m closing it.