--- tags: viruses, SARS-CoV-2 --- [![hackmd-github-sync-badge](https://hackmd.io/GgVBkkl8QeudwZFfJRHvxA/badge)](https://hackmd.io/GgVBkkl8QeudwZFfJRHvxA) [TOC] __News collection__ Collection of news that might be transformed into new variant profiles if needed. * DESH ENA upload: https://www.ebi.ac.uk/ena/browser/view/PRJEB44987 * COG-UK mutation visuals and also antigenic potential: http://sars2.cvr.gla.ac.uk/cog-uk/ * nice dashboard: https://cov-spectrum.ethz.ch/ * 2021-05-04 updated and comprehensive list of VOC/VOI/VUI by the ECDC: https://www.ecdc.europa.eu/en/covid-19/variants-concern * Public virology code from ECDC bioinformatics, variant horizon scoring (__vocal-style?__) * https://github.com/erikalmecdc/ecdc_virology/blob/main/assigned_variants.csv * outbreak.info resources: * https://github.com/outbreak-info/outbreak.info/blob/master/web/src/assets/genomics/curated_mutations.json * "Sites in SARS-CoV-2 RBD where mutations reduce binding by antibodies / sera": https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/ * https://filogeneti.ca/CoVizu/ * cool viz of mutations and frequency compared among pangolin lineages: https://outbreak.info/compare-lineages?gene=S&gene=ORF1a&gene=ORF1b&threshold=75 * We would like to notify you of a cluster of SARS-CoV-2 infections in Lannion, Brittany, caused by a new variant under investigation in France. Available GISAID accession numbers: EPI_ISL_1118892, EPI_ISL_1111064 It concerns a variant of clade 20C, with 9 mutations in the spike protein: * S:H66D, S:G142V, S:D215G, S:V483A, S:D614G, S:H655Y, S:G669S, S:Q949R, S:N1187D * And the following deletions: ORF6:K23-, ORF6:V24-, ORF6:S25-, ORF6:I26-, ORF6:W27-, ORF6:N28-, ORF6:L29-, ORF6:D30-, ORF6:Y31-, S:Y144- The cluster, detected start of January 2021 in a geriatric unit of a hospital of 700 beds, includes 79 cases with symptoms suggestive of COVID-19 as of 13 March (patients and staff; 19 of the infected patients deceased). * 11.03.2021 erschien das neue PHE-Technical Briefing 7 zu den neuen Virusvarianten in UK * Die Liste der s.g. "Virus under inverstigation" (VUI) wird immer länger. Es sind nun insgesamt 4 VOC (B.1.1.7, B.1.1.7 + E484K, B.1.351, P.1.) und 5 VUI (P.2., A.23.1 with E484K, B.1.525, B.1.318, B.1.324.1) in diesem Bericht beschrieben. Darüber hinaus gibt es noch 4 "Variants in Monitoring": B.1.429 zuerst in Kalifornien entdeckt, B.1.526 zuerst in New York entdeckt, B.1.1.7 with S494P zuerst entdeckt in UK, A.27 erstmals in Mayotte entdeckt. * Erstmals wurde P.1. auch in UK nachgewiesen. * New article on recurrent deletions in the Spike protein and its effect on antigenicity. All recurrent deletions are in the NTD domain. They introduce the following nomenclature: Recurrent deletion region 1 (RDR1): ~67-69; RDR2: ~139-145; RDR3: ~210; RDR4: ~242-244. Not surprisingly, deletions in epitope regions cause resistance to antibodies targetting that domain. https://doi.org/10.1126/science.abf6950 * https://github.com/phe-genomics/variant_definitions * https://sarscoverage.org/ --> SARS-CoV-2 lineage dynamics * http://clingen.igib.res.in/esc/ , a comprehensive ressource of immune escape variants * We would like to inform you that we have observed in Portugal an increase in frequency of a SARS-CoV-2 variant carrying Spike D614G+L452R mutations (belonging to Nextstrain clade 20D and the recently classified C.16 Pango lineage). Sequencing data revealed that it increased from a relative frequency of <1% in November 2020 to 6.8 % in January 2021, showing geographic dispersion from 3 to 32 municipalities, respectively. Viruses with Spike L452R mutation have been shown to escape neutralization by some monoclonal antibodies (Li et al, 2020, Cell; https://www.sciencedirect.com/science/article/abs/pii/S0092867420308771; Liu et al, 2020, bioRxiv, https://www.biorxiv.org/content/10.1101/2020.11.06.372037v1). The L452R mutation has also recently emerged independently multiple times worldwide, being associated, for instance, with the B.1.429 lineage (Nextstrain 20C /S:452R) first identified in California (https://www.cdph.ca.gov/Programs/OPA/Pages/NR21-020.aspx). * WHO published definitions for variants of concern (VOC) and variants of interest (VUI): https://www.who.int/publications/m/item/covid-19-weekly-epidemiological-update * nice summaries and visuals! https://outbreak.info/situation-reports * Viral dynamics in B.1.117 vs. non B.1.117: Longer time of infectiousness/viral load above a random threshold. https://dash.harvard.edu/handle/1/37366884 * I found this pre-print on virus variants from the US with S:677 polymorphisms. They describe a few variants, might be interesting for the hackmd: Emergence in late 2020 of multiple lineages of SARS-CoV-2 Spike protein variants affecting amino acid position 677 https://www.medrxiv.org/content/10.1101/2021.02.12.21251658v1.full.pdf * Public Health England published yesterday a statement on 2 new VUI/VOC: https://www.gov.uk/government/news/phe-statement-on-variant-of-concern-and-new-variant-under-investigation * Both have the mutation E484K, one descending from the B.1.1.7 line. There is not much information, but at least they have a name now: * __VUI202102/01__ is characterised by the presence of the E484K spike protein mutation and a small number of other mutations. It is derived from lineage A.23, which is seen internationally, but the E484K additional mutation on this lineage has only been seen within the UK. It was first identified by Public Health England (PHE) on 10 January, while investigating a cluster of 5 cases linked to members of staff from a hospital in Liverpool. So far, 55 cases of this variant have been found. * __VOC202102/02__ is a specific cluster characterised by the presence of the E484K spike protein mutation on the VOC202012/01 SARS-CoV-2 B1.1.7 variant that was first detected in the UK at the end of 2020. Through genomic sequencing and enhanced contact tracing, PHE have so far identified 21 cases of VOC202102/02 across the UK, predominantly centred upon an outbreak in the South West of England. * Two papers describing case studies where mutations (especially deletions) occured in immuno-compromised patients with persistent infection. These cases may be major drivers of SARS-CoV-2 evolution and the emergence of VOCs https://www.nejm.org/doi/full/10.1056/NEJMc2031364?query=main_nav_lg and https://www.sciencedirect.com/science/article/pii/S0092867420314562?via%3Dihub * Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape https://science.sciencemag.org/content/early/2021/02/02/science.abf6950 * The chance of dying is around 35% higher for people who are confirmed to be infected with the new variant. The risk is most pronounced for older men. The chance of death for an 85-year-old man increases from about 17% to nearly 22% for those confirmed to be infected with the variant. Researchers caution that the data are preliminary, and it is not clear whether the variant is deadlier than previous strains or is spreading to more people who are vulnerable to severe disease. https://doi.org/10.1101/2021.02.01.21250959 * New Variant indentified in the UK: B.1.1.7 with E484K mutation: "The COG-UK dataset (total sequences 214,159) was analysed on 26/01/2021. The spike protein mutation E484K (found in VOC 202012/02 B1.351 and VOC 202101/02 P1) has been detected in 11 B1.1.7 sequences. Preliminary information suggests more than one acquisition event" [Technical briefing (PHE, p.17)](https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/957504/Variant_of_Concern_VOC_202012_01_Technical_Briefing_5_England.pdf) * A recurrent SARS-CoV-2 Nsp-1 deletion variant identified in China that reduces the innate immunity interferon response * https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(21)00045-7 * 11aa deletion in Nsp-1 * Increased Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7 to Antibody Neutralization https://www.biorxiv.org/content/10.1101/2021.01.25.428137v2.full.pdf > B.1.1.7 is refractory to neutralization by most mAbs to the N-terminal domain (NTD) of spike and relatively resistant to a number of mAbs to the receptor-binding domain (RBD). It is modestly more resistant to convalescent plasma (~3 fold) and vaccinee sera (~2 fold). B.1.351 is not only refractory to neutralization by most NTD mAbs but also by multiple individual mAbs to the receptor-binding motif on RBD, largely due to an E484K mutation. Moreover, B.1.351 is markedly more resistant to neutralization by convalescent plasma (~11-33 fold) and vaccinee sera (~6.5-8.6 fold). * Neutralization of B.1.117 and B.1.351 by serum from Moderna (mRNA-1273) vaccinees (https://www.biorxiv.org/content/10.1101/2021.01.25.427948v1) > RBD mutations (K417N + E484K + N501Y + D614G) and full B.1.351 mutations (RBD + NTD) resulted in 2.7 and 6.4-fold reduced neutralization. On the other hand, B.1.17 does not confer resistance. * [mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants](https://www.biorxiv.org/content/10.1101/2021.01.15.426911v1) > However, activity against SARS-CoV-2 variants encoding E484K or N501Y or the K417N:E484K:N501Y combination was reduced by a small but significant margin. * Pfizer/BioNtech vaccince BNT162b2 still effective against B.1.1.7 pseudovirus with many Spike mutations (https://www.biorxiv.org/content/10.1101/2021.01.18.426984v1) > The immune sera had equivalent neutralizing titers to both variants. These data, together with the combined immunity involving humoral and cellular effectors induced by this vaccine, make it unlikely that the B.1.1.7 lineage will escape BNT162b2-mediated protection. * Worrying data from South Africa: " The blood samples from half the people we tested showed that all neutralizing activity was lost. This suggests that they may no longer be protected from re-infection." https://www.nicd.ac.za/can-i-be-re-infected-with-the-new-variant-if-ive-had-covid-19/ * and a variant (B.1.429) with L452R in the spike (and two other mutations) is seen more frequently around California since November (the variant is already known for a longer time, but becomes more frequently as it seems). https://www.cdph.ca.gov/Programs/OPA/Pages/NR21-020.aspx * Paper on: "mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants" outlining major resistance mutations (VOC list). https://doi.org/10.1101/2021.01.15.426911 # SARS-CoV-2 variant profiles __Private space__ --- __Disclaimer__ This is a regularly updated collection of publicly available information on important SARS-CoV-2 variants, their lineages & naming, mutations, and, if possible, some phenotypic information. Colleagues in the UK (mostly from the group of A. Rambaut) already maintain an excellent resource to live track the new lineages: https://cov-lineages.org/global_report.html. Another nice ressource to check for mutations globally: https://wan-bioinfo.shinyapps.io/GESS/ __This resource is continuously updating and not all information (such as nucleotide positions, phenotypes, ...) are immediately added and might change according to new findings!__ __Please add a comment if you observe some mistakes or if you want to report important findings. We will check the comments and integrate the information.__ --- __Overview & HowTo__ ![](https://wan-bioinfo.shinyapps.io/GESS/_w_7e34ccfa/Viral-structure-v3.jpg) > From [https://wan-bioinfo.shinyapps.io/GESS/](https://wan-bioinfo.shinyapps.io/GESS/). ![](https://i.imgur.com/HA4E7tl.jpg) > Importantly, the genome size of the SARS-CoV-2 varies from 29.8 kb to 29.9 kb and its genome structure followed the specific gene characteristics to known CoVs; the 5′ more than two-thirds of the genome comprises orf1ab encoding orf1abpolyproteins, while the 3′ one third consists of genes encoding structural proteins including surface (S), envelope (E), membrane (M), and nucleocapsid N proteins (Fig. 1 ). Additionally, the SARS-CoV-2 contains 6 accessory proteins, encoded by ORF3a, ORF6, ORF7a, ORF7b, and ORF8 genes. Source: [PMC7161481](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161481/) ![](https://i.imgur.com/T6hPflt.jpg) ![](https://i.imgur.com/GqQBqtJ.png) > Generated by MF1 and can be updated with further VOCs, ... __Variants Nomenclature__ - Variants are described by the string: `<gene>:<variant description>` for Amino acid variants and `<variant description>` for genomic variants - `<gene>` is the name of the protein (one of `{S, E, M, ORF1ab, ORF3a, ORF6a, ORF7a, ORF7b, ORF8, N, ORF10}`) - `<Variant description>` varies according to the type of variant (substitution, deletion, etc.). Those are described below. - **Substitution** variants: reported by providing the original amino acid, its position, and the 'new' amino acid (regular expression `[A-Z]\d+[A-Z]`). The character `*` denotes a stop codon. It is the same way for genomic positions (`[ACGT]\d+[ACGT]`) - `S:N501Y`: Amino acid change from N to Y at position 501 in the `S` protein - `A23063T`: The mutation above was due to a nucleotide change at position 23,063 from `A` to `T`. <!--- listed by the location of a mutation, e.g. in the spike protein (S:) - the letter after : indicates the original amino-acid, the number the position in the spike protein, and the last letter, the 'new' amino-acid. ---> - **Deletion** variants: the nomenclature is slightly different for amino acids or for genomic sequences: - For amino acids, first the string of Amino acid deleted, then the range of positions that are concerned by the deletion and finally `del` keyword (`[A-Z]+\d+-\d+del`)<br> `orf1ab:SGF3675-3677del`: the 3 amino acids `SGF` are deleted from `orf1ab`<br> `S:Y144-144del` : a 1 amino acid deletion in `S` - For genomic sequences, it starts with the `del` keyword followed by the first position of the deletion and finally the number of deleted characters <br> `del:11288:9`: 9 nucleotides deleted from position 11,288 - **Insertion** variants: None are documented until now, but a possible nomenclature could be to follow the nomenclature of deletionsand using the `ins` keyword - `HV69-70ins` - `ins:21767:6:ATGATC` Note that the first position of a sequence is 1. If possible, we report the Amino acids variant supplemented with its genomic position in an additional colum (using the Wuhan sequence as reference). <!-- __Some examples:__ * `S:N501Y` | `A23063T` * denotes an amino acid change from N to Y in the Spike protein at position 501 due to a nucleotide change at position 23,063 from A to T. --> --- ## VOC: United Kingdom: VOC 202012/01 (old VUI-202012/01, also B.1.1.7 or 20B/501Y.V1) __General__ * South East of England on 14 Dec 2020 ([COG-UK Report](https://www.cogconsortium.uk/news_item/update-on-new-sars-cov-2-variant-and-how-cog-uk-tracks-emerging-mutations/)) * "how long B.1.1.7 might have been spreading in the United States. Quick answer- since November for California and Florida" [Phylogenetic evidence that B.1.1.7 has been circulating in the United States since early- to mid-November](https://virological.org/t/phylogenetic-evidence-that-b-1-1-7-has-been-circulating-in-the-united-states-since-early-to-mid-november/598) * might be more deadly https://doi.org/10.1101/2021.02.01.21250959 __Important mutations__ * B.1.1.7 lineage (20B/501Y.V1) has 17 amino acid substitutions relative to the initial SARS-CoV-2 genome sequence [source](https://virological.org/t/detection-of-non-b-1-1-7-spike-69-70-sequences-b-1-375-in-the-united-states/587) * Mainly obtained from [https://cov-lineages.org/global_report_B.1.1.7.html](https://cov-lineages.org/global_report_B.1.1.7.html). * Matching nucleotide positions from [https://virological.org/t/preliminary-genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-the-uk-defined-by-a-novel-set-of-spike-mutations/563](https://virological.org/t/preliminary-genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-the-uk-defined-by-a-novel-set-of-spike-mutations/563) * does __not have__ the K417N/K417T and E484K mutation like known for SA B.1.351 and Brazil B.1.1.28 and P.1. * resistance to NTD binding antibodies [10]. | gene | amino acid | nucleotide | comment | | ---- | ---- | ---- | ---- | | ORF1ab | T1001I | C3267T | | | ORF1ab | A1708D | C5388A | | | ORF1ab | I2230T | T6954C | | | ORF1ab | SGF3675-3677del | del:11288:9 | _:9_ denotes the nucleotide length of the deletion. A deletion spanning 3 codons. [Also found in the SA B.1.351 and Brazil/Japan B.1.1.248 variant](https://twitter.com/richardneher/status/1348739384191946758/photo/1). Some thoughts from the same tweet: A. Rambaut: "Little is known about ns6 function I think, but it is transmembrane and the deletion is in an external loop." "Orf1 is a popular target in the RT-PCR tests. Would be interesting to see if the oligos annheal on that stretch. Any variant that escapes test detection will gain in fitness." "The deletion makes the largest outside loop of nsp6 shorter (nsp6 induces the double-membrane replication vesicles where the RNA is transcripted)". Also in Brazil P.1 | | S | HV69-70del | del:21765:6 | In-frame 6 nt deletion. As also seen in variants [S:N439K](https://github.com/hodcroftlab/covariants#sn439k) & [S:Y453F](https://github.com/hodcroftlab/covariants#sy453f). Recurrent del described in [Kemp et al 2020](https://www.biorxiv.org/content/10.1101/2020.12.14.422555v3). Also found in [US samples](https://virological.org/t/identification-of-a-novel-sars-cov-2-spike-69-70-deletion-lineage-circulating-in-the-united-states/577). | | S | Y144-144del | del:21991:3 | !!Mutation also associated with (NTD-targeting) AB escape!! [13] | | S | N501Y | A23063T | Mutation in RBD, needed for binding to ACE2. N501Y was also found in longitudinally-collected samples from an immunocompromised patient ([Choi et al. NEJM](https://www.nejm.org/doi/full/10.1056/NEJMc2031364?query=featured_coronavirus)). Mutation seems to increase ACE2 binding (in vitro) [3] and ?transmissibility?| | S | A570D | C23271A | | | S | D614G | A23403G | | | S | P681H | C23604A | Adjacent to the furin cleavage site. Also found in Nigeria lineage B.1.1.207 | | S | T716I | C23709T | | | S | S982A | T24506G | | | S | D1118H | G24914C | | | ORF8 | Q27* | C27972T | Becoming a stop codon, thus truncated ORF8. Deletion of ORF8 was previously associated with reduced clinical severity ([Young et al. Lancet](https://www.thelancet.com/article/S0140-6736(20)31757-8/fulltext)) | | ORF8 | R52I | G28048T | | | ORF8 | Y73C | A28111G | | | N | D3L | GAT28280CTA | | | N | S235F | C28977T | | [3] https://doi.org/10.1101/2021.01.06.425392 [13] https://doi.org/10.1126/science.abf6950 __Phenotype__ * ~50% higher transmissibility TODO LINK LITERATURE * Literature on neutralization by convalescent antibodies https://doi.org/10.1101/2021.01.18.427166 __Situation in Germany (Jan 25)__ * at least 51 cases in Germany * Berlin, Baden-Württemberg, Bayern, Hessen, Niedersachsen, Nordrhein-Westfalen, Sachsen und Schleswig-Holstein * 2/3 of DETECTED cases have exposure in a foreign county (!this information may be highly biased!) --- ## VOC: South Africa: 501.V2 (also B.1.351 or 20H/501Y.V2 (formerly 20C/501Y.V2)) __General__ * South Africa, announced in December 2020 ([Tegally et al., medRxiv](https://www.medrxiv.org/content/10.1101/2020.12.21.20248640v1)) __Important mutations__ * Mainly from [https://cov-lineages.org/global_report_B.1.351.html](https://cov-lineages.org/global_report_B.1.351.html). Details in [Tegally _et al._ 2020](https://www.medrxiv.org/content/10.1101/2020.12.21.20248640v1.full.pdf). * __does not have S:69/70del in spike like UK B.1.1.7!__ * [Scientists noted](https://www.who.int/docs/default-source/blue-print/who-com-statement_new-variant_rev1.pdf) that the variant contains several mutations that allow it to attach more easily to human cells because of the following three mutations in the receptor-binding domain (RBD) in the spike glycoprotein of the virus: N501Y, K417N, and E484K * [SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma](https://www.biorxiv.org/content/10.1101/2021.01.18.427166v1) * resistance to NTD and RBD binding antibodies * __Nucleotide positions here need double-check!__ (derived from a table of variants send internally for a SA case in Tuebingen, maybe shifted by one nt) | gene | amino acid | nucleotide | comment | | ---- | ---- | ---- | ---- | | ORF1ab | K1655N| G5230T | __is this part of orf1ab?__ | | ORF1ab | SGF3675-3677del | del:11288:9 | [Also found in the UK B.1.1.7 and Brazil/Japan P.1 lineage](https://twitter.com/richardneher/status/1348739384191946758/photo/1). See B.1.1.7 for details about this 3 codon deletion. Also found in Brazil P.1 | | S | L18F | C21614T | N-terminal domain; resistance to antibodies (Abs) | | S | D80A | C21801T | N-terminal domain; resistance to Abs | | S | D215G | C22206T | N-terminal domain; resistance to Abs | | S | R246I | ? | | | S | K417N | G22813T | RBD; Resistance to Abs | | S | E484K | G23012A | RBD. [Reinfection in Brasil](https://virological.org/t/spike-e484k-mutation-in-the-first-sars-cov-2-reinfection-case-confirmed-in-brazil-2020/584) also haboring S:E484K. Classical SARS-CoV-2 reinfection case with the emerging Brazilian lineage B.1.1.28(E484K); Resistance to Abs | | S | N501Y | A23063T | RBD; associated with fitness/transmissibility [3]| | S | D614G | A23403G | | | S | A701V | C23664T | loop 2 | | ORF3a | Q57H | G25563T | | | ORF3a | S171L | C25904T | | | E | P71L | C26456T | | | N | T205I | C28887T | | __Phenotype__ * putative resistance to vaccine-elicited or natural immunity caused by 'wildtype' infection * __Situation in Germany (Jan 25)__ * at least 19 cases in Germany * Baden-Württemberg, Hamburg, Hessen, Nordrhein-Westfalen und Sachsen * Most cases have exposure in South Africa, except one case (!this information may be highly biased!) --- ## VOC: Brazil, Manaus: P.1 __General__ * [2021-01-12, Genomic characterisation of an emergent SARS-CoV-2 lineage in Manaus: preliminary findings](https://virological.org/t/genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-manaus-preliminary-findings/586) * new lineage, named [P.1](https://cov-lineages.org/lineages/lineage_P.1.html) (descendent of Brazil [B.1.1.28](https://cov-lineages.org/lineages/lineage_B.1.1.28.html)) * from Manaus, northern Brazil, Amazonas * unique constellation of lineage defining mutations, including several mutations of known biological importance such as E484K, K417T, and N501Y * the same found in the Brazil travelers that were sequenced in Japan * P.1 lineage carries 17 unique amino acid changes, 3 deletions, and 4 synonymous mutations, and one 4nt insertion > The set of mutations/deletions shared between P.1, B.1.1.7, and the B.1.351 lineages appear to have arisen entirely independently. * resistance to NTD and RBD binding antibodies [10] * 2021-01-19: [SARS-CoV-2 reinfection by the new Variant of Concern (VOC) P.1 in Amazonas, Brazil](https://virological.org/t/sars-cov-2-reinfection-by-the-new-variant-of-concern-voc-p-1-in-amazonas-brazil/596) > This report describes the first confirmed case of reinfection with the P.1 lineage in a 29-years-old female resident in the Amazonas state, Brazil, previously infected with a B.1 lineage virus. __Important mutations__ | gene | amino acid | nucleotide | comment | | ---- | ---- | ---- | ---- | | ORF1ab | SGF3675-3677del | del:11288:9 | [Also found in the UK B.1.1.7 and SA B.1.351 variant](https://twitter.com/richardneher/status/1348739384191946758/photo/1). See B.1.1.7 for details about this 3 codon deletion| | S | L18F | C21614T| also in SA B.1.351 | | S | T20N | ?| | | S | P26S | ?| | | S | D138Y | ?| | | S | R190S | ?| | | S | K417T | A22812C| RBD. Like in SA B.1.351 but K417T instead of K417N. K417T also in Brazil travelers detected in Japan (makes sense bc/ they arrived from northern Brazil P.1). | | S | E484K | G23012A| RBD. Also known in South Africa B.1.351 and Brazil travelers arrived in Japan (B.1.1.248-like) strain. [Region that a number of antibodies seem to recognize](https://blogs.sciencemag.org/pipeline/archives/2020/12/22/the-new-mutations)| | S | N501Y | A23063T| RBD. Like in UK B.1.1.7 and SA B.1.351 variant| | S | D614G | ?| | | S | H655Y | ?| | | S | T1027I| ?| | | S | V1176F| ?| | | ORF8 | E92K | ?| | | ORF8 | | insertion28269-28273 | not in frame? 4nt | | N | P80R | ? | | __Phenotype__ * --- ## VOI: B.1.525 * Jan, 2021 A new variant arose in the UK, that aquired the 484K mutation. In Germany: 12 appearances until Feb. 16th in DESH data. * Another new lineage worth monitoring is B.1.525. Just designated: https://t.co/d05u4L72pC * spike mutations E484K, Q677H, F888L plus the 2 deletions seen in B.1.1.7 spike 69-70, 144 and the nsp6 deletion seen in B.1.1.7, B.1.351 and P.1. * how was this lineage defined in `pangolin`: https://github.com/cov-lineages/pango-designation/issues/4 | gene | amino acid | nucleotide | comment | | ---- | ---- | ---- | ---- | | S | E484K | | | | S | D614G | | | | S | Q677H | | | --- ## VOI: Californian Variants (B.1.427 & B.1.429; Cal.20C/S:452R) * variant detected in California; has mutation L452R __Mutations__ <!-- * also has spike:W152C orf1ab:D5584Y and N:T205I [see](https://cov-lineages.org/lineages/lineage_B.1.429.html) --> | gene | amino acid | nucleotide | comment | | ---- | ---- | ---- | ---- | | ORF1a| I4205V | ? | - | | ORF1b| D1183Y | ? | - | | S | S13I | ? | NTD - epitope | | S | W152C | ? | NTD -epitope | | S | L452R | ? | RBD; probably related to increased transmissibility; possible resistence to some monoclonal antibodies, but not to reconvalescent plasma [12] | __Phenotype__ * Probably more transmissible (strong evidence/prevalence increasing) [13] * Potentially more deadly (weak evidence/sample size limitation) [13] * closely related variant: B.1.428 * In this study, we demonstrate that two recently emerging mutations in the receptor binding domain of the SARS-CoV-2 spike protein, L452R (in B.1.427/429) and Y453F (in B.1.298), can escape from the HLA-24-restricted cellular immunity [14] * Not only the escape from the HLA-A24-restricted cellular immunity, these mutations also reinforce the affinity to viral receptor ACE2. And notably, the L452R mutation increases protein stability, viral infectivity, and potentially promotes viral replication [14] https://www.biorxiv.org/content/10.1101/2021.04.02.438288v1 https://doi.org/10.1001/jama.2021.1612 [13] __https://doi.org/10.1126/science.abh2101__ --- ## VOI: B.1.617.1/B.1.617.3 ("Indian" variant) * The [Guardian seems](https://www.theguardian.com/world/2021/apr/15/covid-variant-first-detected-india-found-uk) to be talking a fair bit about what they're calling an "Indian variant" * 8 in DESH (2021-04-17) * It has E484Q and not the very concerning E484K, And P681R instead of P681H known from B.1.1.7 (but yeah... same positions. that are affected). __Mutations__ | gene | amino acid | nucleotide | comment | | ---- | ---- | ---- | ---- | | S | L452R | | | | S | E484Q | | | | S | D614G | | | __Phenotype__ * --- ## VOI: B.1.617.2 ("Indian" variant) * The [Guardian seems](https://www.theguardian.com/world/2021/apr/15/covid-variant-first-detected-india-found-uk) to be talking a fair bit about what they're calling an "Indian variant" * 8 in DESH (2021-04-17) * It has E484Q and not the very concerning E484K, And P681R instead of P681H known from B.1.1.7 (but yeah... same positions. that are affected). __Mutations__ | gene | amino acid | nucleotide | comment | | ---- | ---- | ---- | ---- | | S | L452R | | | | S | T478K | | | | S | D614G | | | __Phenotype__ * --- ## VOI: B.1.620 >>>- Lithuania claimed they discovered a new lineage in their country probably originating in Africa, with additional sequences in Turkey and also Germany. They posted the following prototypic sequences: EPI_ISL_1540680, EPI_ISL_1404880 Sebastien: It is now an official pango lineage called B.1.620. I can give you more info about it as we are involved because we also detected this lineage last week in Central African Republic (we are also active there). We were about to push a post on virological to put a flag on it wen we realized that Baele and Dudas were probably reporting about the same thing - we now shared our sequences w/ them. This lineage is kind of a horror show (S477N, E484K, P681H and ALL deletions found in VOC/VOI) and it has apparently spread very fast in the last 2 months (detected in 7 countries in Europe, the US, Cameroon and CAR). __Mutations__ | gene | amino acid | nucleotide | comment | | ---- | ---- | ---- | ---- | | S | S477N | | | | S | E484K | | | | S | D614G | | | __Phenotype__ * --- ## VOI: B.1.621 __Mutations__ | gene | amino acid | nucleotide | comment | | ---- | ---- | ---- | ---- | | S | R346K | | | | S | E484K | | | | S | N501Y | | | | S | D614G | | | __Phenotype__ * --- ## VOI: P.3 | gene | amino acid | nucleotide | comment | | ---- | ---- | ---- | ---- | | S | E484K | | | | S | N501Y | | | | S | D614G | | | __Phenotype__ * --- ## VOI: B.1.616 (France) | gene | amino acid | nucleotide | comment | | ---- | ---- | ---- | ---- | | S | V482A | | | | S | D614G | | | | S | H655Y | | | | S | G669S | | | __Phenotype__ * --- ## VUM: Variant under monitoring: A.23.1+E484K (Uganda) And another one, which also immediately gets its lineage of concern report (https://cov-lineages.org/global_report_A.23.1.html). This time it is an A lineage, which became ultradominant in Uganda in a matter of weeks, has already started international spread and shares strikingly similar changes w/ the 3 main VOCs, incl. several aa changes in spike (one at pos 613 w/ effects that might be close to D614G) and changes in nsp6 (in the same zone where del 11288:9 is found) and ORF7,8 and 9. 10:35 https://www.medrxiv.org/content/10.1101/2021.02.08.21251393v1 * #SARSCoV2 lineage A #variant (A.23.1) with altered spike is dominating the current #Uganda epidemic. Preprint co-authored by EVBC members: https://www.medrxiv.org/content/10.1101/2021.02.08.21251393v2 * https://cov-lineages.org/global_report_A.23.1.html * International lineage with variants of biological significance F157L, V367F, Q613H and P681R, described fully in the preprent: Bugembe et al 2021. Q613H is predicted to be functionally equivalent to the D614G mutation that arose early in 2020. __Mutations__ | gene | amino acid | nucleotide | comment | | ---- | ---- | ---- | ---- | | S | F157L | | | | S | V367F | | | | S | E484K | | | | S | Q613H | | close to the wide-spread D614G | | S | P681R | | | __Phenotype__ * --- ## VUM: B.1.526 (New York) * another (potential?) VoC from New York. B.1.526 that increased in frequency over the last 3 months (https://www.medrxiv.org/content/10.1101/2021.02.23.21252259v1) __Mutations__ | gene | amino acid | nucleotide | comment | | ---- | ---- | ---- | ---- | | S | L5F | | | | S | T95I | | | | S | D253G | | | | S | E484K | | | | S | D614G | | | | S | A701V | | | __Phenotype__ * --- ## VUM: B.1.526.1 (New York) __Mutations__ | gene | amino acid | nucleotide | comment | | ---- | ---- | ---- | ---- | | S | L452R | | | | S | D614G | | | --- ## VUM: B.1.526.2 (New York) __Mutations__ | gene | amino acid | nucleotide | comment | | ---- | ---- | ---- | ---- | | S | S477N | | | | S | D614G | | | --- ## VUM: A.27 * emerging in France * we detected two sequences in recent RKI lab network sequencing data 2021-03-25 * 400 sequences in DESH, 2021-03-26 * almost all of them send from Baden-Wuerttemberg (border France) __Mutations__ | gene | amino acid | nucleotide | comment | | ---- | ---- | ---- | ---- | | S | L452R | | | | S | N501Y | A23063T | RBD | | S | H655Y | | | __Phenotype__ * --- ## VUM: A.28 __Mutations__ | gene | amino acid | nucleotide | comment | | ---- | ---- | ---- | ---- | | S | E484K | | | | S | N501T | | | | S | H655Y | | | __Phenotype__ * --- ## VUM: C.36+L452R (B.1.1.1.36) sub-variant For your information, a sub-variant of the C.36 (Pango Lineage alias for B.1.1.1.36) virus, with extensive additional substitutions in the spike protein, has been detected in a transmission cluster in Norway in March. The virus was imported with a traveler from Egypt. The virus possesses the following substitutions in the spike protein (example: EPI_ISL_1579173): S12F; W152R; D253Y; R346S; L452R; D614G; Q677H; A899S; ΔH69-V70. The deletion is found in the B.1.1.7 variant first seen in Kent and has been reported to be related to antigenic drift. W152R, R346S and L452R are in antibody recognition sites, and might be involved in antigenic drift. L452R is also the key change in the California-variant. A899S is involved in subunit oligomerisation. S12F is in the N-terminal domain and might also influence antigenicity. No further transmissions have been detected beyond this single cluster. A BLAST search in GISAID has revealed similar viruses elsewhere in Europe. The C.36 lineage otherwise seems to be more prevalent in Egypt. More information on variants in Norway can be fond in the weekly report https://www.fhi.no/en/publ/2020/weekly-reports-for-coronavirus-og-covid-19/ Risk Assessment Due to the specific mutations and number of changes in the spike-protein it is not unlikely that the virus has altered transmission abilities or can evade host immunity to some degree. As this virus also have been detected in some European countries it will be important to look out for these in the virological surveillance. Information from Egypt on the prevalence of this mutated variant of the C.36 virus is highly desired. We are looking forward to an updated risk assessment on VOCs from ECDC." __Mutations__ | gene | amino acid | nucleotide | comment | | ---- | ---- | ---- | ---- | | S | L452R | | | | S | D614G | | | __Phenotype__ * --- ## NEW VARIANT TEMPLATE * PLEASE MAKE A COPY OF THIS SECTION AND THEN UPDATE TO ENTER A NEW VARIANT __Mutations__ | gene | amino acid | nucleotide | comment | | ---- | ---- | ---- | ---- | | | | | | __Phenotype__ * # Variant cruft (not really monitorred or on any "official" VOC/VOI/VUM lists) --- ## Nigeria: B.1.1.207 __General__ * [first detected in August 2020](https://virological.org/t/detection-of-sars-cov-2-p681h-spike-protein-variant-in-nigeria/567) * two SARS-CoV-2 sequences that share one non-synonymous SNP in the spike protein in common with B.1.1.7, but none of the other unique lineage-defining mutations of B.1.1.7 * [B.1.1.207](https://cov-lineages.org/lineages/lineage_B.1.1.207.html) split from [South Africa lineage B.1.1.53](https://cov-lineages.org/lineages/lineage_B.1.1.53.html) __Important mutations__ * [none of the other 22 unique lineage-defining mutations shared with B.1.1.7](https://virological.org/t/detection-of-sars-cov-2-p681h-spike-protein-variant-in-nigeria/567) | gene | amino acid | nucleotide | comment | | ---- | ---- | ---- | ---- | | S | P681H | C23604A | [https://virological.org/t/detection-of-sars-cov-2-p681h-spike-protein-variant-in-nigeria/567](https://virological.org/t/detection-of-sars-cov-2-p681h-spike-protein-variant-in-nigeria/567). Shared in common with B.1.1.7. | __Phenotype__ * implications for transmission and virulence [are unclear](https://virological.org/t/detection-of-sars-cov-2-p681h-spike-protein-variant-in-nigeria/567) --- ## Japan/Tokyo: B.1.1.28(K417N/E484K/N501Y) (four travelers from northern Brazil, now named lineage P.1) __General__ * labeled __B.1.1.28(K417N/E484K/N501Y)__ according to a [post from 2021-01-11](https://virological.org/t/phylogenetic-relationship-of-sars-cov-2-sequences-from-amazonas-with-emerging-brazilian-variants-harboring-mutations-e484k-and-n501y-in-the-spike-protein/585) * belongs to the B.1.1.248 strain, separated from B.1.1.28 (Brazil) * B.1.1.248 was reassigned B.1.1.28 ([source](https://cov-lineages.org/lineages.html)) * later assigned to the Brazilian P.1 lineage * [detected in four travelers from Brazil’s Amazonas state](https://www.japantimes.co.jp/news/2021/01/11/national/science-health/new-coronavirus-variant-japan/) * the new variant has 12 mutations, one of which is also present in the variants found in the U.K. and South Africa (N501Y) * [share some of the mutations in common with those of concern for increased infectivity](https://www.niid.go.jp/niid/ja/diseases/ka/corona-virus/2019-ncov/10107-covid19-33.html). * In Brazil, there are reports of reinfection cases with mutant strains showing the E484K mutation of the B.1.1.248 strain (2021/01/06; reassigned B.1.1.28 ([sourve](https://cov-lineages.org/lineages.html))), but they are not the same as the new mutant strain according to [NIID](https://www.niid.go.jp/niid/ja/diseases/ka/corona-virus/2019-ncov/10107-covid19-33.html) __Important mutations__ * information obtained from [NIID](https://www.niid.go.jp/niid/ja/diseases/ka/corona-virus/2019-ncov/10107-covid19-33.html) and this [Figure](https://www.niid.go.jp/niid/images/epi/corona/covid19-33-fig.png) * __emerged from the Brazil B.1.1.28 lineage__ and has 12 mutations in the spike protein, the NIID said * __Nucleotide positions here need double-check!__ (derived from a table of variants send internally for a SA case in Tuebingen, maybe shifted by one nt) | gene | amino acid | nucleotide | comment | | ---- | ---- | ---- | ---- | | orf1ab | SGF3675-3677del | del:11288:9 | [Also found in the UK B.1.1.7 and SA B.1.351 variant](https://twitter.com/richardneher/status/1348739384191946758/photo/1). See B.1.1.7 for details about this 3 codon deletion. Also found in Brazil P.1 | | S | L18F | C21614T| resistance to Abs| | S | T20N | ?| | | S | P26S | ?| | | S | D138Y | ?| | | S | R190S | ?| | | S | K417T | A22812C| like in SA B.1.351 but K417T instead of K417N according to this [NIID figure](https://www.niid.go.jp/niid/images/epi/corona/covid19-33-fig.png); resistance to Abs | | S | E484K | G23012A| RBD. Like in SA B.1.351 and Brasil P.1 ([likely re-infection causing](https://virological.org/t/spike-e484k-mutation-in-the-first-sars-cov-2-reinfection-case-confirmed-in-brazil-2020/584)); Resistance to Abs| | S | N501Y | A23063T| RBD. Like in UK B.1.1.7 and SA B.1.351 variant| | S | D614G | A23403G| | | S | H655Y | ?| | | S | T1027I| ?| | | S | V1176F| ?| | __Phenotype__ * no clear evidence of the mutated viruses being associated with more severe disease outcomes --- ## Brazil: B.1.1.28 __General__ * [B.1.1.28 brasilian lineage](https://cov-lineages.org/lineages/lineage_B.1.1.28.html) * [Spike E484K mutation in the first SARS-CoV-2 reinfection case confirmed in Brazil, 2020](https://virological.org/t/spike-e484k-mutation-in-the-first-sars-cov-2-reinfection-case-confirmed-in-brazil-2020/584) __Important mutations__ * [no N501Y in the Brazil base lineage B.1.1.28](https://virological.org/t/genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-manaus-preliminary-findings/586) but now found in the Brazil P.1 (see below) | gene | amino acid | nucleotide | comment | | ---- | ---- | ---- | ---- | | S | E484K | G23012A | Also known in South Africa B.1.351 and P.1 (Brazil, seen in Japan from Brazilian travelers). [Region that a number of antibodies seem to recognize](https://blogs.sciencemag.org/pipeline/archives/2020/12/22/the-new-mutations)| __Phenotype__ * caused re-infection: "Whole-genome sequencing revealed that the two infections were caused, respectively, by the two most prevalent SARS-CoV-2 Brazilian lineages B.1.1.33 (primo-infection) and B.1.1.28 (reinfection)." --- ## Italy predecessor to B.1.1.7 "UK" variant __General__ * based on from Eric Topol [tweet](https://twitter.com/EricTopol/status/1349140550188888064) > A predecessor to the B.1.1.7 "UK" variant was seen in Italy in August in a 59-year-old man with persistent covid infection and accelerated viral evolution * see [Fiorentini _et al._ 2021 (The Lancet Infect Disease)](https://doi.org/10.1016/S1473-3099(21)00007-4) > It is worth noting that the N501T substitution was detected in both MB61-Nov and MB61-Aug SARS-CoV-2 isolates, highlighting that a mutation at the critical amino acid residue 501 was already present in Italy in August, 2020 > spike N501T variants emerged in early August (95% highest posterior density early July to end of August) in northern Italy (appendix), and therefore that SARS-CoV-2 strains harbouring a substitution at position 501 might have circulated unnoticed even before the end of September, 2020 __Important mutations__ | gene | amino acid | nucleotide | comment | | ---- | ---- | ---- | ---- | | S | N501T | ? | RBD. Not __Y__ like in UK B.1.1.7 and SA B.1.351 variant. | | S | Q493K | ? | RBD. "Differently from B.1.1.7, the MB61 variants showed a second mutation ... that, together with N501T, might alter the binding affinity of the spike protein to the ACE2 receptor | __Phenotype__ * --- ## US B.1.375 (20C/501Y.V2), non-B.1.1.7 Spike del69/70 __General__ * [Detection of non-B.1.1.7 Spike ∆69/70 sequences (B.1.375) in the United States](https://virological.org/t/detection-of-non-b-1-1-7-spike-69-70-sequences-b-1-375-in-the-united-states/587) __Mutations__ * contains S ∆69/70, but no other B.1.1.7 mutations [source](https://virological.org/t/detection-of-non-b-1-1-7-spike-69-70-sequences-b-1-375-in-the-united-states/587) | gene | amino acid | nucleotide | comment | | ---- | ---- | ---- | ---- | | ORF1a | T1828A | A5747G | | | ORF1b | E1264D | G17259T | | | ORF3a | T151I | C25884T | | | S | HV69-70del | del:21765:6 | In-frame 6 nt deletion. Also found in UK-found B.1.1.7. | | M | I48V | A26664G | | __Phenotype__ * --- ## Columbus Ohio: two novel clade 20C/G variants Isolate 1 __General__ * [Distinct Patterns of Emergence of SARS‐CoV‐2 Spike Variants including N501Y in Clinical Samples in Columbus Ohio](https://www.biorxiv.org/content/10.1101/2021.01.12.426407v1.full.pdf) * We report here the emergence in Columbus, Ohio in December 2020 of two novel SARS‐CoV‐2 clade 20C/G variants * COH/20G/501Y sample __Mutations__ Isolate 1: | gene | amino acid | nucleotide | comment | | ---- | ---- | ---- | ---- | | S | Q677H | G23593T | | | M | A85S | G26775T | | | N | D377Y | G29402T | | __Phenotype__ --- ## Columbus Ohio: two novel clade 20C/G variants Isolate 2 __General__ * [Distinct Patterns of Emergence of SARS‐CoV‐2 Spike Variants including N501Y in Clinical Samples in Columbus Ohio](https://www.biorxiv.org/content/10.1101/2021.01.12.426407v1.full.pdf) * We report here the emergence in Columbus, Ohio in December 2020 of two novel SARS‐CoV‐2 clade 20C/G variants * COH/20G/501Y sample __Mutations__ Isolate 2: two markers of the UK‐B.1.1.7 but lacks all other mutations | gene | amino acid | nucleotide | comment | | ---- | ---- | ---- | ---- | | S | N501Y | A23063T | RBD | | ORF8 | R52I | G28048T | | __Phenotype__ --- ## Garmisch-Partenkirchen Variant (B.1.1.134) * variant detected in Garmisch-Partenkirschen (Bavaria, Germany) does not have typical B.1.1.7 mutations such as N501Y, but has the same deletion del69/70 in the Spike like B.1.1.7. (https://www.zdf.de/nachrichten/panorama/coronavirus-mutation-garmisch-partenkirchen-100.html#xtor=CS5-62). * almost certain that this is __not__ a VOC, probably irrelevant observation, (del69/70 w/o N501Y, likely to be an N439K variant found as the reason of the so-called S-gene target failures in Germany) __Phenotype__ * __Situation in Germany__ * 3 cases so far --- ## B.1.1.33 (Brazil) * https://virological.org/t/identification-of-a-new-b-1-1-33-sars-cov-2-variant-of-interest-voi-circulating-in-brazil-with-mutation-e484k-and-multiple-deletions-in-the-amino-n-terminal-domain-of-the-spike-protein/675 * Identification of a new B.1.1.33 SARS-CoV-2 Variant of Interest (VOI) circulating in Brazil with mutation E484K and multiple deletions in the amino (N)-terminal domain of the Spike protein __Mutations__ | gene | amino acid | nucleotide | comment | | ---- | ---- | ---- | ---- | | ORF1ab | P822L | C5184T | | | ORF1ab | P108S | C10376T | | | | P132S | C10478T | | | ORF1ab | V149A | T11418C | | | S | P9L | C21588T | | | S | 141-144del | del:21984:12 | | | S | I210V | A22190G | | | S | 211del | del:22193:3 | | | S | L212I | T22196A | | | S | 256-258del | del:22327:9 | | | S | V445A | T22896C | | | S | E484K | G23012A | | | ORF7b | | del:27794:5 | frame-shifted and truncated | | N | Q70R | A28482G | | __Phenotype__ * --- ## A.VOI.V2 * This new VOI, temporarily designated A.VOI.V2, has 31 amino acid substitutions (11 in spike) and three deletions (all in spike) (Figure 1C & 1D). The spike mutations include three substitutions in the receptor-binding domain (R346K, T478R and E484K); five substitutions and three deletions in the N-terminal domain, some of which are within the antigenic supersite (Y144Δ, R246M, SYL247-249Δ and W258L)4; and two substitutions adjacent to the S1/S2 cleavage site (H655Y and P681H) (https://www.medrxiv.org/content/10.1101/2021.03.30.21254323v1.full) __Mutations__ | gene | amino acid | nucleotide | comment | | ---- | ---- | ---- | ---- | | | | | | __Phenotype__ * --- # Putative Antibody escape mutations Spike RBD binding antibodies The majority of patient-derived antibodies are RBD binding (68-80%) [2]. ?However, these ABs are less potent than NTD-binding ABs? Human neutralizing monoclonal antibodies to the SARS-CoV-2 RBD can be categorized as belonging to 4 different classes based on their target regions on the RBD. Class 1 and 2 antibodies are among the most potent and also the most abundant antibodies. These antibodies target epitopes that overlap or are closely associated with RBD residues K417, E484 and N501. They are frequently sensitive to mutation in these residues and select for K417N, E484K and N501Y mutations. **VOI alert region: 400-501: Nucleotides: 22760-23065** | gene | amino acid | nucleotide | comment | REF | | ---- | ---- | ---- |---- | ---- | | S | E406W | ? |therapeutic AB (REGN10933,REGN10987)|1 | | S | K417N | G22813T/G22813C |therapeutic AB (LY-CoV 016), Moderna vaccine (mRNA-1273) elicited AB-response| 1,9| | S | N439K | ? |therapeutic AB (RREGN10987)| 1| | S | N440D | ? |persistent infection| 1| | S | K444Q | ? |therapeutic AB (REGN10987)|1 | | S | K444-G446 | ? |therapeutic AB (REGN10987) contact region, serum derived AB|1,4,5 | | S | L452R | ? |serum antibodies |6 | | S | N460T | ? |therapeutic AB (LY-CoV 016)|1 | | S | A475V | ? |therapeutic AB (LY-CoV 016)|1,6 | | S | V483A | ? |serum RBD binding AB|6 | | S | E484K | ? |serum RBD binding AB; Moderna (mRNA-1273) elicited vaccine response|4,9 | | S | E484Q | ? |serum RBD binding AB; Moderna (mRNA-1273) elicited vaccine response|4,9 | | S | E484P | ? |serum RBD binding AB; Moderna (mRNA-1273) elicited vaccine response|4,9 | | S | F486K | ? |therapeutic AB (REGN10933)|1 | | S | F486I | ? |persistent Infection|1 | | S | Y489H | ? |persistent infection|1 | | S | F490L | ? |monoclonal antibody, serum derived|5, 6| | S | Q493K | ? |persistent Infection,therapeutic AB (REGN10933) |1 | | S | N501Y | ? |vaccine induced and serum RBD AB |7 | [1] https://doi.org/10.1126/science.abf9302 [2] https://doi.org/10.1101/2021.01.14.426475 [4] https://doi.org/10.1101/2020.12.31.425021 [5] https://doi.org/10.7554/elife.61312 [6] https://doi.org/10.1016/j.cell.2020.07.012 [7] https://doi.org/10.1101/2021.01.15.426911 * Literature on neutralization escape by RBD mutations K417N, E484K and N501Y https://doi.org/10.1101/2021.01.18.427166 # Putative Antibody escape mutations Spike NTD binding antibodies Some antibodies (AB) are N-terminal domain (NTD) binding (6-20%) [2]. ?These seem to be more potent than RBD bindings ABs?. Interpretation: If mutations occur in the AB binding domain, they may lead to partial resistance. **VOI alert regions**: | gene | amino acid | nucleotide | comment | REF | | ---- | ---- | ---- |---- | ---- | | S | 14-20 | 21602-21622 |B-cell derived AB|2 | | S | 140-158 | 21980-22036 |B-cell derived AB| 2| | S | 245-264 | 22295-22354 |B-cell derived AB| 2| Of particular concern: 144del [13]; N234Q [6]; mutation in 246 [2] https://doi.org/10.1101/2021.01.14.426475 [13] https://doi.org/10.1126/science.abf6950 # Summary Important mutations (VOC region) in Spike and putative phenotype | gene | amino acid | nucleotide | comment | | ---- | ---- | ---- |---- | | S | S13I | ? | NTD epitope; detected in the californian variant B.1.429 [11] | | S | L18F | C21614T |resistance to NTD binding antibodies [2] | | S | T20N | C21621A |resistance to NTD binding antibodies [2] | | S | P26S | C21638T |resistance to NTD binding antibodies [2] | | S | HV69-70del | del:21765:6 |Recurrent deletion region 1 (RDR1) [13]; S-target primer dropout | | S | D80A | C21801T |resistance to NTD binding antibodies [2] | | S | D138Y | G21974T |resistance to NTD binding antibodies [2] | | S | Y144-144del | del:21992:3 | Recurrent deletion region 2 (RDR2) [13] !!Mutation associated with NTD binding AB escape!! [2,10,13] | | S | W152C | ? | NTD epitope; detected in the californian variant B.1.429 [11] | | S | R190S | G22132C/G22132T |resistance to NTD binding antibodies [2] | | S | I210del | del:22189:3 |Recurrent deletion region 3 (RDR3) [13]| | S | LAL242-244del | del:22286:9 |Recurrent deletion region 4 (RDR4) [13]; resistance to NTD binding antibodies[10] | | S | R246I | G22299T |resistance to NTD binding antibodies[2,10] | | S | K417T | A22812C |resistance to RBD binding antibodies[1,9,10] | | S | K417N | G22813C/G22813T |resistance to RBD binding antibodies[1,9,10] | | S | L452R | ? | detected in the Californian variant B.1.429 [11]; probably related to increased transmissibility; in very close proximity to the mink (cluster 5) variant F453Y; possible resistence to some monoclonal antibodies, but not to reconvalescent plasma [12] | | S | A475V | C22986T | vaccine-elicited antibody resistance [8]| | S | S477N | G22992A | Mutation seems to increase ACE2 binding (in vitro) [3], also AB resistance [7]| | S | S477G | A22991G | Mutation seems to increase ACE2 binding (in vitro) [3], also AB resistance [7]| | S | E484K | G23012A |strong resistance to RBD binding AB [4,9,10] | S | E484Q | G23012C |strong resistance to RBD binding AB [4,9,10] | S | E484P | G23012C+A23013C |strong resistance to RBD binding AB [4,9,10] | S | E484K,N501Y | G23012A,A23063T | Combination seems to strongly increase ACE2 binding (in vitro), resistance to RBD ABs [3,4]| | S | E484K,R683G | G23012A,C23609G | !!Combination seems to cause insusceptibility to to vaccine elicited ABs!! [8]| | S | F486S | T23019C | strong resistance to RBD binding antibodies[7]| | S | Q493K | C23039A | resistance to RBD binding antibodies[1,8]| | S | Q493R | A23040G | resistance to RBD binding antibodies[1,8]| | S | N501Y | A23063T | Mutation seems to increase ACE2 binding (in vitro)[3], ?also partial resistance [8]?| [3] https://doi.org/10.1101/2021.01.06.425392 [7] https://doi.org/10.1101/2020.11.06.372037 [8] https://doi.org/10.1101/2021.01.15.426911 [9] https://doi.org/10.1101/2021.01.25.427948 [10] https://doi.org/10.1101/2021.01.25.428137 [11] https://doi.org/10.1001/jama.2021.1612 [12] https://doi.org/10.1016/j.cell.2020.07.012 [13] https://doi.org/10.1126/science.abf6950 --- # Positive selection A great ressource to check positively (and negatively) selected sites calculated based on GISAID data: * http://covid19.datamonkey.org/ * https://observablehq.com/@spond/revised-sars-cov-2-analytics-page * [deep mutational scanner](https://dms-view.github.io) Here, we also aim to collect interesting sites under selection pressure from literature and other resources. | gene | amino acid | nucleotide | date of detection | significance | comment | | ---- | ---- | ---- |---- | ---- | ---- | --- # Clades Based on https://virological.org/t/updated-nextstain-sars-cov-2-clade-naming-strategy/581 At this moment, major clades from 2020 onwards are: * 20A: basal pandemic lineage bearing S 614G that’s globally distributed * 20B: derived from 20A bearing N 203K, N204R and ORF14 50N, also globally distributed * 20C: derived from 20A bearing ORF3a 57H and ORF1a 265I, also globally distributed * 20D: derived from 20B bearing ORF1a 1246I and ORF1a 3278S, concentrated in South America, southern Europe and South Africa * 20E: derived from 20A bearing N 220V, ORF10 30L, ORF14 67F and S 222V, concentrated in Europe * 20F: derived from 20B bearing ORF1a 300F and S 477N, concentrated in Australia * 20G: derived from 20C bearing ORF1b 1653D, ORF3a 172V, N 67S and N 199L, concentrated in the United States * 20H/501Y.V2: derived from 20C bearing S 80A, S 215G, S 484K, S 501Y, S 701V, concentrated in South Africa * 20I/501Y.V1: derived from 20B bearing S 501Y, S 570D, S 681H, ORF8 27*, concentrated in the United Kingdom --- # Additional Sources * https://www.nytimes.com/interactive/2021/health/coronavirus-variant-tracker.html * [Genomic coordinates for B.1.1.7, P.1, and B.1.351, 0-based! (in my opinion, these are all shifted by one base)](https://gist.github.com/nekrut/cc588b67b22bc117d41bc9379d0e15ec) * [GisAID Tool to track VOCs](https://www.gisaid.org/hcov19-variants/) * [https://en.wikipedia.org/wiki/Variants_of_SARS-CoV-2](https://en.wikipedia.org/wiki/Variants_of_SARS-CoV-2) * [Genome and protein viewer (ensemble; Spike)](https://covid-19.ensembl.org/Sars_cov_2/Transcript/Sequence_cDNA?db=core;g=ENSSASG00005000004;r=MN908947.3:21563-25384;t=ENSSAST00005000004) * [Deep mutational scanner](https://dms-view.github.io) dms-view.github.io * [https://virological.org/](https://virological.org/) * Important and up-to-date ressource, early and updated blog posts * [https://github.com/hodcroftlab/covariants#20aeu1](https://github.com/hodcroftlab/covariants#20aeu1) * CoVariants: SARS-CoV-2 Mutations and Variants of Interest (https://covariants.org/) * really good overvie including protein 3d structures and information about phaenotypes, a lot of information above is extracted from here * [Mutations arising in SARS-CoV-2 spike on sustained human-to-human transmission and human-to-animal passage](https://virological.org/t/mutations-arising-in-sars-cov-2-spike-on-sustained-human-to-human-transmission-and-human-to-animal-passage/578) ![](https://i.imgur.com/Sr5NpdD.jpg) * [Naturally occurring indels in multiple coronavirus spikes](https://virological.org/t/naturally-occurring-indels-in-multiple-coronavirus-spikes/560) * [WHO: Variant analysis of SARS-CoV-2 genomes](https://www.who.int/bulletin/volumes/98/7/20-253591/en/) ![](https://i.imgur.com/j0xsPvl.jpg) --- # Martin Notes Needs to be integrated.. gosh... * Nice picture https://twitter.com/EricTopol/status/1371964594613198854?s=09 * recombination check: https://virological.org/t/recombinant-sars-cov-2-genomes-involving-lineage-b-1-1-7-in-the-uk/658 * Sergei Pond read: https://www.medrxiv.org/content/10.1101/2021.02.23.21252268v1 * B.1.258∆, a SARS-CoV-2 variant with ∆H69/∆V70 in the Spike protein circulating in the Czech Republic and Slovakia: https://virological.org/t/b-1-258-a-sars-cov-2-variant-with-h69-v70-in-the-spike-protein-circulating-in-the-czech-republic-and-slovakia/613 * P.3: https://github.com/cov-lineages/pango-designation/issues/27