Evolution of the C.1 lineage in South Africa with multiple Spike mutations - pre-print at: medrxiv.org/content/10.110… - In this tweet thread, I highlight this lineage (assigned as C.1.2), the potential impact of the mutations, and the likelihood that this become a variant of concern
The C.1.2 has 14 mutations in Spike, including three mutations at the Receptor Binding Motif, the Y449H, E484K, and N501Y - two of the mutations have been found in three of the four variants of concern (Alpha, Beta, and Gamma).
In relationship to decrease neutralization, in addition to the E484K, there are also deletions at position 144 and positions 242-243, the 144 deletions are also seen in the Alpha and the 242-243 in the Beta, which associates with a decrease neutralization of antibodies
There is also the N679K, which is a mutation just upstream of the S1/S2 furin cleavage including Q675H/R, Q677H/P, N679K, and P681H/R have occurred independently in many SARS-CoV-2 global lineages.
In addition, there is also a mutation at 655 positions, the H655Y mutation, which in the 3-D structure of Spike it cluster very close to the S1/S2 furin. Around 8% (i.e. 7/95) of the sequences have also added the P681H found in the Alpha VOC.
The constellations of mutations worry us as they seem The C.1.2 end up adding multiple mutations that are similar to the Beta with extra mutations at S1/S2 and NTD. Now let me talk more about the C.1 lineages that emerged and persisted in southern Africa.
The C.1 was one of the lineages that dominated the first wave of the pandemic in South Africa. The emergence of this lineage is well described in the paper by Tegally et al. Nature Medicine 2021 - nature.com/articles/s4159…
The C.1 emerged in the centre of South Africa (probably Gauteng) and spread quickly to most of the provinces in South Africa during the first wave of infections in 2020.
The C.1 was also introduced in neighbouring countries and gave rise to a new clade, the C.1.1 in Mozambique, which added the S477N mutation at the RBM and A688S close to the S1/S2. The emergence of the C.1.1. is seen in a pan-Africa analysis pre-print medrxiv.org/content/10.110…
We now have the C.1.x persisting for over 1 year in South Africa and now evolving to C.1.2 further to add a dozen new mutations at Spike. We are now working with @sigallab & Penny Moore to describe the effect of the mutations in a live virus and pseudo virus system.
The reason why we decided to publish the preprint is that we see the C.1.2 persistence in South Africa and is now in another 10 countries. It is early days as only 95 genomes have been published at GISAID. However, we found that in this pandemic is share info quicker than later.
This is the work of dozens of scientists as part of the Network of Genomic Surveillance in South Africa (NGS-SA). The pre-print analysis was lead by @NICD and @krisp_news and it also involves a very bright and young women scientist, Catherine Scheepers, who is the first author.
Pre-print of C.1.2, which will be updated soon with neutralization results at: medrxiv.org/content/10.110…

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More from @Tuliodna

9 Sep
Because the pandemic is very fast-moving, we are updating every week the results of our pan-African collaboration published in Science today at: genomics.africa/sars-cov-2-das…
SARS-CoV-2 variants in lineages in African countries
This is the work of 100s of authors from 122 African organizations, see the author list and please credit their work! See: Wilkinson et al. Science 2021 - science.org/doi/10.1126/sc…
Read 5 tweets
9 Sep
'Although distorted by low sampling numbers and blind spots, the findings highlight that Africa must not be left behind in the global pandemic response, otherwise it could become a source for new variants'. science.org/doi/10.1126/sc…
So many people to thank! 100s of authors from Africa and funders to believe that we can do high-level science that influences public health response - Thanks, @RockefellerFdn @RickABright @fdesouza @illumina @thermofisher @stevensonmarkp @WHOAFRO @AfricaCDC @dsigovza
The most rewarding part of this collaboration was the holistic approach of trust and capacity building! What to say! African dream team working together @christian_happi @houzhou @Mittenavoig @EduanWilkinson @rjlessells
Read 4 tweets
23 Jul
Seems that the level4 restrictions in South Africa helped to control the third wave of #COVID19 - Reproductive number < 1 in the whole country and in most provinces.
The Western Cape and Eastern Cape seem to have peaked now, R =1
Gauteng #COVID19 cases are really in the downward path, R = 0.6
Read 5 tweets
30 Jun
NGS-SA worked hard to increase sequencing in South Africa. We know now that the explosive #COVID19 third wave is dominatedd by the Delta variant.

In this tweet thread, we present recent data (sampled up to 24 June in many provinces in SA, including Gauteng) - Tweet 1/8
This graph shows the distribution of the variants over time in the different provinces. 2/8
The third wave in Gauteng was caused by the Delta variant, thanks to @nicd_sa and @krisp_news who worked day and night on the weekend to increase genomics surveillance in Gauteng.
Graph shows Black line = Daily cases (7-day average), Yellow = Beta, Green = Delta. Tweet 3/8
Read 8 tweets
17 Jun
A Novel and Expanding SARS-CoV-2 Variant, B.1.1.318, dominates infections in Mauritius medrxiv.org/content/10.110…
Mauritius is an example of controlling #COVID19 in Africa, with 1,700 infections and only 18 deaths. However, one variant seems to have caused the great majority of all of the infections
Mauritius has stopped dozens of introductions of the Beta (501Y.V2/B.1.351) and Alpha (B.1.1.7) but the B.1.1.318, which has the 484K mutation (common to Beta) and the 681H mutation (common to Alpha) has caused all local transmitted cases.
Read 14 tweets
3 Jun
In this online pre-print, we present a case of persistent SARS-CoV-2 infection with accelerated intra-host evolution in a patient with advanced HIV and antiretroviral treatment failure in South Africa.

Paper deposited at medRxiv &available at: krisp.org.za/publications.p… @sigallab
SARS-CoV-2 RT-PCR was positive for 216 days (27 weeks). At all time-points between day 0 and day 216 there was a mean Ct ranging from 16.4 to 31.6. The patient had HIV drug resistance and was not responding to therapy.
Over 30 mutations accumulated over time, many of them changing aminoacids that are common of variants of concern.
Read 15 tweets

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