Difference between revisions of "deLemus"

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='''<big>Update(27/12/2022)</big>'''=
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__NOTOC__
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''Dynamic Expedition of Leading Mutations in SARS-CoV-2 Spike Glycoproteins''
  
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<html><iframe width="1100" height="525" src="https://docs.google.com/spreadsheets/d/e/2PACX-1vT6heuYwqnms3FjO2IgXcJjcmk3vCTm6o4ZQvzpa7pM83sc3212WE48M2q-1TmZXSv3YScW7YonpiQO/pubhtml?gid=0&single=true"></iframe></html>
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</br>
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<img width="1100" height="525" src="https://drive.google.com/file/d/140NDKxSZ0YWKwDwfRe0fTYNif5aigtCk/view?usp=sharing"></img>
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The dynamic epidemiology of coronavirus disease 2019 (COVID-19) since its outbreak has been a result of the continuous evolution of its etiological agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Within the first 2 years of this pandemic, the World Health Organization (WHO) has already announced 4 variants of concern (VOC), namely alpha (B.1.1.7), beta (B.1.351), gamma (P.1), and delta (B.1.617.2), together with numerous variants of interest (VOI). The latest lineage to be designated a VOC would be omicron (B.1.1.529),<ref name="Karim" /> from which a diverse variant soup is generated.<ref>Callaway, E. COVID ‘variant soup’ is making winter surges hard to predict. ''Nature'' '''611,''' 213 (2022).</ref> From the original BA.1 strain of November 2021 to the most recent XBB and BQ.1 strains of late 2022,<ref name="Wang" /><ref name="European Centre" /> each omicron subvariant has successively proliferated and outcompeted its once dominant antecedent.<ref name="Del Rio" /> The emergence of all these variants has brought along many novel mutations that continue to fine-tune the fitness of the virus,<ref>Carabelli, A. M. ''et al.'' SARS-CoV-2 variant biology: Immune escape, transmission and fitness. ''Nat Rev Microbiol'' (2023). DOI: https://doi.org/10.1038/s41579-022-00841-7.</ref><ref>Witte, L. ''et al.'' Epistasis lowers the genetic barrier to SARS-CoV-2 neutralizing antibody escape. ''Nat Commun'' '''14,''' 302 (2023).</ref> leading to its persistent global circulation. Recent emerging variant (EV) data retrieved from GISAID, as of 17 January 2023, has revealed that the top 4 most rapidly spreading lineages are the BA.1.1.22, CH.1.1, XBB.1.5, and BQ.1.1 variants, among which XBB.1.5 has been found to be especially prevalent in the US,<ref>Callaway, E. Coronavirus variant XBB.1.5 rises in the United States — is it a global threat? ''Nature'' '''613,''' 222 (2023).</ref> making up of more than 40% of its sequence coverage in early January 2023.
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<img>[http://45.77.11.65:9080/i/2022/12/26/63a9b3883b363.png]</img>
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 +
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==Spike Glycoprotein==
 +
The spike glycoprotein of SARS-CoV-2 is a trimeric type I viral fusion protein that binds the virus to the angiotensin-converting enzyme 2 (ACE2) receptor of a host cell.<ref name="Jackson2021"/> It is composed of 2 subunits: the N-terminal subunit 1 (S1) and C-terminal subunit 2 (S2), within which multiple domains lie. The S1 region facilitates ACE2 binding and is made up of an N-terminal domain (NTD), a receptor-binding domain (RBD), and 2 C-terminal subdomains (CTD1 and CTD2), while the downstream S2 region is responsible for mediating virus-host cell membrane fusion.
  
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==Summary==
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<htmltag tagname="img" src="https://wiki.laviebay.hkust.edu.hk/deLemus/RESEARCH_TEAMS/images/PublishedPlot/Domains.png" alt="test for htmltag img" class="wikimg" style="display: block;width:70%;margin-left: auto;margin-right: auto;"></htmltag>
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<big>The deLemus website provides information about the leading mutations of in spikes glycoprotein of SARS-CoV-2. From the leading mutations, we can investigate the mutation patterns of the virus, allowing further research on their functions and possibly prediction of new variants in the future. Omicron, the latest SARS-CoV-2 lineage designated as a VOC by the WHO after being reported in South Africa in November 2021, has various subvariants, including BA.1 (the first subvariant of omicron), BA.2, BA.4, and BA.5. Omicron was spreading very quickly to many countries after its first report. Soon after the discovery of BA.1, BA.2 was detected and spread across the globe. In April 2022, BA.4 and BA.5 were monitored by the WHO after being found in multiple countries, and they showed a significant increase in growth advantage when compared to BA.2. These two variants became dominant in the UK, the US, and Germany in June 2022. In the meantime, BA.2.12.1 and BA.2.75 were also spreading in the US and India respectively in May 2022. In August 2022, XBB, a recombinant of BA.2.10.1 and BA.2.75, was found to have a small outbreak in various countries such as Singapore and Bangladesh. After that, in October 2022, BQ.1, which is a subvariant of BA.5 prevalent in France, was found.
+
=='''Update'''==
 +
The identified leading mutations in 2023 are listed as follows <ref name="deLemus" />:
 +
 
 +
<tabs>
 +
 
 +
<tab name="2023.12">
 +
<htmltag tagname="img" src="https://wiki.laviebay.hkust.edu.hk/deLemus/RESEARCH_TEAMS/images/PublishedPlot/2023-12.png" alt="test for htmltag img" class="wikimg" style="display: block;width:100%;margin-left: auto;margin-right: auto;"></htmltag>
 +
 
 +
===2023.12.01-2023.12.17===
 +
{| class="wikitable"
 +
|-
 +
! Outlined Mutations !! Confirmed in VOC/Emerging Variants
 +
|-
 +
| <span style="color:burlywood;">'''L455F'''</span> || EG.5.1.1
 +
|-
 +
| <span style="color:burlywood;">'''A475V'''</span> || EG.5.1.1
 +
|-
 +
| <span style="color:hotpink;">'''E654K'''</span> || HK.3
 +
|}
 +
 
 +
</tab>
 +
 
 +
<tab name="2023.11">
 +
<htmltag tagname="img" src="https://wiki.laviebay.hkust.edu.hk/deLemus/RESEARCH_TEAMS/images/PublishedPlot/2023-11.png" alt="test for htmltag img" class="wikimg" style="display: block;width:100%;margin-left: auto;margin-right: auto;"></htmltag>
 +
 
 +
===2023.11.01-2023.11.17===
 +
{| class="wikitable"
 +
|-
 +
! Outlined Mutations !! Confirmed in VOC/Emerging Variants
 +
|-
 +
| <span style="color:yellowgreen;">'''N185D'''</span> || HK.3.2
 +
|-
 +
| <span style="color:burlywood;">'''L455F'''</span> || EG.5.1.1
 +
|-
 +
| <span style="color:burlywood;">'''A475V'''</span> || JF.1
 +
|-
 +
| <span style="color:hotpink;">'''T572I'''</span> || FY.2
 +
|-
 +
| <span style="color:hotpink;">'''Q613H'''</span> || XBB.1.16
 +
|-
 +
| <span style="color:cornflowerblue;">'''D1153Y'''</span> || HK.3
 +
|}
 +
 
 +
</tab>
 +
 
 +
<tab name="2023.10">
 +
<htmltag tagname="img" src="https://wiki.laviebay.hkust.edu.hk/deLemus/RESEARCH_TEAMS/images/PublishedPlot/2023-10.png" alt="test for htmltag img" class="wikimg" style="display: block;width:100%;margin-left: auto;margin-right: auto;"></htmltag>
 +
 
 +
===2023.10.06===
 +
{| class="wikitable"
 +
|-
 +
! Outlined Mutations !! Confirmed in VOC/Emerging Variants
 +
|-
 +
| <span style="color:burlywood;">'''L455F'''</span> || EG.5.1.1
 +
|-
 +
| <span style="color:burlywood;">'''A475V'''</span> || GK.1
 +
|}
 +
 
 +
</tab>
 +
 
 +
<tab name="2023.09">
 +
<htmltag tagname="img" src="https://wiki.laviebay.hkust.edu.hk/deLemus/RESEARCH_TEAMS/images/PublishedPlot/2023-09.png" alt="test for htmltag img" class="wikimg" style="display: block;width:100%;margin-left: auto;margin-right: auto;"></htmltag>
 +
 
 +
===2023.09.08-2023.09.28===
 +
{| class="wikitable"
 +
|-
 +
! Outlined Mutations !! Confirmed in VOC/Emerging Variants
 +
|-
 +
| <span style="color:burlywood;">'''R403K'''</span> || BA.2.86 (Pirola)
 +
|-
 +
| <span style="color:burlywood;">'''L455F'''</span> || EG.5.1.1
 +
|-
 +
| <span style="color:burlywood;">'''S494P'''</span> || EG.5.1.1
 +
|-
 +
| <span style="color:burlywood;">'''P521S'''</span> || XBB.1.16.15
 +
|-
 +
| <span style="color:hotpink;">'''E554K'''</span> || BA.2.86 (Pirola) & FE.1
 +
|-
 +
| <span style="color:hotpink;">'''Q613H'''</span> || BA.2.86 (Pirola)
 +
|-
 +
| <span style="color:hotpink;">'''P621S'''</span> || BA.2.86 (Pirola)
 +
|-
 +
| <span style="color:cornflowerblue;">'''T732I'''</span> || XBB.2.3 x XBB.1.5
 +
|-
 +
| <span style="color:cornflowerblue;">'''S939F'''</span> || BA.2.86 (Pirola)
 +
|-
 +
| <span style="color:cornflowerblue;">'''V1264L'''</span> || CK.1.1
 +
|}
 +
 
 +
</tab>
 +
 
 +
<tab name="2023.08">
 +
<htmltag tagname="img" src="https://wiki.laviebay.hkust.edu.hk/deLemus/RESEARCH_TEAMS/images/PublishedPlot/2023-08.png" alt="test for htmltag img" class="wikimg" style="display: block;width:100%;margin-left: auto;margin-right: auto;"></htmltag>
 +
 
 +
<big>Here are the recently confirmed leading mutations.</big>
 +
 
 +
===2023.08.04 - 2023.08.22===
 +
{| class="wikitable"
 +
|-
 +
! Outlined Mutations !! Confirmed in VOC/Emerging Variants
 +
|-
 +
| <span style="color:yellowgreen;">'''N185D'''</span> || XBB.1.5
 +
|-
 +
| <span style="color:yellowgreen;">'''L212S'''</span> || FY.4.2
 +
|-
 +
| <span style="color:burlywood;">'''V445A'''</span> || XBC.1.6
 +
|-
 +
| <span style="color:burlywood;">'''L455F'''</span> || EG.5.1.1
 +
|-
 +
| <span style="color:burlywood;">'''F456L'''</span> || EG.5.1 (Eris)
 +
|-
 +
| <span style="color:hotpink;">'''E554Q'''</span> || XBB.1.5.18
 +
|-
 +
| <span style="color:hotpink;">'''Q613H'''</span> || XBB.1.16
 +
|-
 +
| <span style="color:cornflowerblue;">'''T883I'''</span> || XBB.1.16
 +
|}
 +
''*The reported mutations of detected variants are from Cov-Lineages<ref name="Cov-Lineages" />''
 +
</br>
 +
===<big>RBD Mutation Profile of Latest VOIs.</big>===
 +
<htmltag tagname="img" src="https://wiki.laviebay.hkust.edu.hk/deLemus/RESEARCH_TEAMS/images/PublishedPlot/2023-08_VarRBD.png" alt="test for htmltag img" class="wikimg" style="display: block;width:65%;margin-left: auto;margin-right: auto;"></htmltag>
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 +
</tab>
 +
 
 +
<tab name="2023.07">
 +
<htmltag tagname="img" src="https://wiki.laviebay.hkust.edu.hk/deLemus/RESEARCH_TEAMS/images/PublishedPlot/2023-07.png" alt="test for htmltag img" class="wikimg" style="display: block;width:100%;margin-left: auto;margin-right: auto;"></htmltag>
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<html>
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 +
* Generated 3D structure of spike protein with highlighted leading mutations (AlphaFold2, colab version 2022).
 +
 
 +
<big>Here are the recently confirmed leading mutations.</big>
 +
 
 +
===2023.06.30 - 2023.07.05===
 +
{| class="wikitable"
 +
|-
 +
! Outlined Mutations !! Confirmed in VOC/Emerging Variants
 +
|-
 +
| <span style="color:yellowgreen;">'''H146K'''</span> || FL.2.3 (XBB.1.9.1.2.3)
 +
|-
 +
| <span style="color:burlywood;">'''S446N'''</span> || FL.19
 +
|-
 +
| <span style="color:burlywood;">'''F456L'''</span> || XBF
 +
|}
 +
 
 +
 
 +
</tab>
 +
 
 +
<tab name="2023.06">
 +
<htmltag tagname="img" src="https://wiki.laviebay.hkust.edu.hk/deLemus/RESEARCH_TEAMS/images/PublishedPlot/2023-06.png" alt="test for htmltag img" class="wikimg" style="display: block;width:100%;margin-left: auto;margin-right: auto;"></htmltag>
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<html>
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 +
* Generated 3D structure of spike protein with highlighted leading mutations (AlphaFold2, colab version 2022).
 +
 
 +
<big>Here are the recently confirmed leading mutations.</big>
 +
 
 +
===2023.06.01 - 2023.06.13===
 +
{| class="wikitable"
 +
|-
 +
! Outlined Mutations !! Confirmed in VOC/Emerging Variants
 +
|-
 +
| <span style="color:burlywood;">'''F490P'''</span> || XBB.1.9.1
 +
|-
 +
| <span style="color:hotpink;">'''E554K'''</span> || XBB.1.9.1 (sublineage)
 +
|-
 +
| <span style="color:hotpink;">'''Q675K'''</span> || XBB.1.22.1
 +
|-
 +
| <span style="color:cornflowerblue;">'''L858I'''</span> || CH.1.1.1
 +
|}
 +
 
 +
 
 +
</tab>
 +
 
 +
<tab name="2023.05">
 +
<htmltag tagname="img" src="https://wiki.laviebay.hkust.edu.hk/deLemus/RESEARCH_TEAMS/images/PublishedPlot/2023-05.png" alt="test for htmltag img" class="wikimg" style="display: block;width:100%;margin-left: auto;margin-right: auto;"></htmltag>
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<html>
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        .molstar {
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    <link rel="stylesheet" type="text/css" href="https://molstar.org/viewer/molstar.css" />
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 +
* Generated 3D structure of spike protein with highlighted leading mutations (AlphaFold2, colab version 2022).
 +
 
 +
<big>Here are the recently confirmed leading mutations.</big>
 +
 
 +
===2023.05.01 - 2023.05.12===
 +
{| class="wikitable"
 +
|-
 +
! Outlined Mutations !! Confirmed in VOC/Emerging Variants
 +
|-
 +
| <span style="color:burlywood;">'''F456L'''</span> || FD.1.1 & EG.5.1 (2023.08)
 +
|-
 +
| <span style="color:burlywood;">'''S494P'''</span> || XBB.2.3 & XBB.1.1
 +
|-
 +
| <span style="color:hotpink;">'''T572I'''</span> || FY.1 ( XBB.1.22.1.1 )
 +
|}
 +
''*The reported mutations of detected variants are from GISAID''
 +
 
 +
 
 +
</tab>
 +
 
 +
<tab name="2023.04">
 +
<htmltag tagname="img" src="https://wiki.laviebay.hkust.edu.hk/deLemus/RESEARCH_TEAMS/images/PublishedPlot/2023-04.png" alt="test for htmltag img" class="wikimg" style="display: block;width:100%;margin-left: auto;margin-right: auto;"></htmltag>
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<html>
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        .molstar {
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 +
* Generated 3D structure of spike protein with highlighted leading mutations (AlphaFold2, colab version 2022).
 +
 
 +
<big>Here are the recently confirmed leading mutations.</big>
 +
 
 +
===2023.04.01 - 2023.04.21===
 +
{| class="wikitable"
 +
|-
 +
! Outlined Mutations !! Confirmed in VOC/Emerging Variants
 +
|-
 +
| <span style="color:yellowgreen;">'''H146K'''</span> || XBB.1.5 & XBB.1.16
 +
|-
 +
| <span style="color:yellowgreen;">'''M153I'''</span> || XBB.2.3.3
 +
|-
 +
| <span style="color:yellowgreen;">'''E180V'''</span> || XBB.1.16
 +
|-
 +
| <span style="color:burlywood;">'''K444R'''</span> || XBB.1.5
 +
|-
 +
| <span style="color:burlywood;">'''T478R'''</span> || XBB.1.16, XBB.1.5, CH.1.1.2 & XBB.2.3
 +
|-
 +
| <span style="color:burlywood;">'''F490P'''</span> || XBB.2.6
 +
|-
 +
| <span style="color:burlywood;">'''S494P'''</span> || XBB.1.5
 +
|-
 +
| <span style="color:hotpink;">'''Q613H'''</span> || XBB.1.16
 +
|-
 +
| <span style="color:hotpink;">'''P621S'''</span> || XBB.2.3
 +
|-
 +
| <span style="color:hotpink;">'''A688V'''</span> || XAY.1.1.1
 +
|}
 +
 
 +
</tab>
 +
 
 +
<tab name="2023.03">
 +
<htmltag tagname="img" src="https://wiki.laviebay.hkust.edu.hk/deLemus/RESEARCH_TEAMS/images/PublishedPlot/2023-03.png" alt="test for htmltag img" class="wikimg" style="display: block;width:100%;margin-left: auto;margin-right: auto;"></htmltag>
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<html>
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        .molstar {
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 +
* Generated 3D structure of spike protein with highlighted leading mutations (AlphaFold2, colab version 2022).
 +
 
 +
<big>Here are the recently confirmed leading mutations.</big>
 +
 
 +
===2023.03.01 - 2023.03.21===
 +
{| class="wikitable"
 +
|-
 +
! Outlined Mutations !! Confirmed in VOC/Emerging Variants
 +
|-
 +
| <span style="color:yellowgreen;">'''Y248S'''</span> || BQ.1
 +
|-
 +
| <span style="color:burlywood;">'''F490P'''</span> || XBB.1 & XBB.1.5
 +
|-
 +
| <span style="color:hotpink;">'''T547I'''</span> || XBB.1.16
 +
|-
 +
| <span style="color:hotpink;">'''Q613H'''</span> || DV.1, CH.1.1.1 & CH.1.1.17
 +
|-
 +
| <span style="color:hotpink;">'''I666V'''</span> || XBB.1.5
 +
|-
 +
| <span style="color:cornflowerblue;">'''V1264L'''</span> || CH.1.1
 +
|}
 +
 
 +
</tab>
 +
 
 +
<tab name="2023.02">
 +
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 +
* Generated 3D structure of spike protein with highlighted leading mutations (AlphaFold2, colab version 2022).
 +
 
 +
<big>Here are the recently confirmed leading mutations.</big>
 +
 
 +
===2023.02.03 - 2023.02.20===
 +
{| class="wikitable"
 +
|-
 +
! Outlined Mutations !! Confirmed in VOC/Emerging Variants
 +
|-
 +
| <span style="color:yellowgreen;">'''K147I'''</span> || XBB.1.5.2.1
 +
|-
 +
| <span style="color:yellowgreen;">'''Y248S'''</span> || BQ.1.1.43
 +
|-
 +
| <span style="color:burlywood;">'''S494P'''</span> || XBB.1.5
 +
|-
 +
| <span style="color:hotpink;">'''Q613H'''</span> || XBB.1.9.2 & XBB.2.4
 +
|-
 +
| <span style="color:hotpink;">'''P612S'''</span> || XBF
 +
|-
 +
| <span style="color:hotpink;">'''T678I'''</span> || BA.2.75 x BA.5
 +
|-
 +
| <span style="color:hotpink;">'''N679R'''</span> || CH.1.1
 +
|-
 +
| <span style="color:cornflowerblue;">'''P1162S'''</span> || XBK.1
 +
|}
 +
''*The reported mutations of detected variants are from GISAID<ref name="GISAID" />''
 +
</tab>
 +
 
 +
<tab name="2023.01">
 +
<htmltag tagname="img" src="https://wiki.laviebay.hkust.edu.hk/deLemus/RESEARCH_TEAMS/images/PublishedPlot/2023-01.png" alt="test for htmltag img" class="wikimg" style="display: block;width:100%;margin-left: auto;margin-right: auto;"></htmltag>
 +
 
 +
<html>
 +
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 +
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 +
</html>
 +
* Generated 3D structure of spike protein with highlighted leading mutations (AlphaFold2, colab version 2022).
 +
 
 +
<big>Here are the recently confirmed leading mutations.</big>
 +
 
 +
===2023.01.31===
 +
{| class="wikitable"
 +
|-
 +
! Outlined Mutations !! Confirmed in VOC/Emerging Variants
 +
|-
 +
| <span style="color:burlywood;">'''V445A'''</span> || BQ.1.1
 +
|-
 +
| <span style="color:cornflowerblue;">'''T883I'''</span> || BQ.1.1
 +
|}
 +
===2023.01.17 - 2023.01.25===
 +
{| class="wikitable"
 +
|-
 +
! Outlined Mutations !! Confirmed in VOC/Emerging Variants
 +
|-
 +
| <span style="color:yellowgreen;">'''H146- / H146K'''</span> || BQ.1.1 / XBB.1.5
 +
|-
 +
| <span style="color:burlywood;">'''F486A'''</span> || BQ.1.1
 +
|-
 +
| <span style="color:hotpink;">'''E583D'''</span> || BQ.1.1
 +
|-
 +
| <span style="color:hotpink;">'''Q613H'''</span> ||  BQ.1.1
 +
|-
 +
| <span style="color:cornflowerblue;">'''S939F'''</span> || BQ.1.1
 +
|}
 +
 
 +
</tab>
 +
 
 +
</tabs>
 +
 
 +
 
 +
<!--
 +
===2023.01.31===
 +
{| class="wikitable"
 +
|-
 +
! Outlined Mutations !! Confirmed in VOC/Emerging Variants !! Conformation
 +
|-
 +
| V445A || BQ.1.1 || Amino acid site located at an RBD epitope<ref name="Weisblum_eLife"/> ; Mutation reduces neutralization by antibody <ref name="CellRep20220517"/>
 +
|}
 +
===2023.01.17 - 2023.01.25===
 +
{| class="wikitable"
 +
|-
 +
! Outlined Mutations !! Confirmed in VOC/Emerging Variants !! Conformation
 +
|-
 +
| H146-/K || BQ.1.1, XBB.1.5 || Amino acid site recognized by mAbs targeting NTD<ref name=":3"/>
 +
|-
 +
| E583D || BQ.1.1 || Viral functions to be confirmed by further investigation
 +
|-
 +
| Q613H ||  BQ.1.1 || Speculate to enhance replicative fitness and transmissibility due to close proximity to D614G ; Potential functions to be elucidated<ref name=":0"/><ref name="Bugembe"/>
 +
|-
 +
| S939F || BQ.1.1 || Destabilize both pre-fusion and post-fusion S2 conformation<ref name="Olivie"/> ; Capable to enhance infectivity and modulate T-cell immune response when combined with D614G<ref name="LiImpactCell"/><ref name="Donzelli"/>
 +
|}
 +
 
 +
<big>The following leading mutations call for special attention with respect to the upcoming variants.</big>
 +
==NTD==
 +
{| class="wikitable"
 +
|-
 +
! Outlined Mutations !! Conformation
 +
|-
 +
| A27P || An antigenic site targeted by the group 3 antibody C1717<ref name=":2" />
 +
|-
 +
| K147- || Involved in interacting with multiple monoclonal antibodies<ref name=":4" /> ; Mutation to threonine (K147T) at this site promotes immune evasion<ref name=":3" />
 +
|-
 +
| N164K || Functional impact to be confirmed in future investigation.
 +
|-
 +
| Q183G || Interactions with surface glycoconjugates mediate the viral attachment<ref name="Sun_Glycobio2021" /> ; Caused a loss of an amide group; May abrogate the hydrogen bond between the amino acid and the carboxylic group of surface sialosides<ref name="Buchanan" />
 +
|-
 +
| N185D || Functional impact to be confirmed in future investigation.
 +
|-
 +
|H245N
 +
|Located in the supersite loop of the NTD antigenic supersite for antibodies SLS28 and S2X333<ref name=":4" /><ref name=":3" /> ; Caused a loss of a positive charge ; Introduces an NXS sequon (<sub>245</sub>NRS<sub>247</sub>) for ''N''-glycosylation
 +
|-
 +
|G252V
 +
|Site is critical for the binding of human antibody COV2-3439<ref>Suryadevara N. ''et al.'' An antibody targeting the N-terminal domain of SARS-CoV-2 disrupts the spike trimer. ''J Clin Invest'' '''132,''' 159062 (2022).</ref>
 +
|-
 +
|G257D
 +
|Located in the supersite loop of the NTD antigenic supersite for antibodies SLS28 and S2X333<ref name=":4" /><ref name=":3" /> ; Caused a gain of negative charge
 +
|-
 +
|A262S
 +
|Enhance the utilization of ACE2 in numerous mammals<ref name="Wang_JMedVirol2022" /> ; May increase interspecies and intraspecies transmissibility
 +
|}
 +
 
 +
==RBD==
 +
{| class="wikitable"
 +
|-
 +
! Outlined Mutations !! Conformation
 +
|-
 +
| R346I/S || Possibly lead to immune evasion due to the disruption of class 3 antibodies binding site<ref name="Gaebler"/> <ref name="WangQ_LancetID2022"/>
 +
|-
 +
| K444N/R || Escape mutations for covalescent plasma<ref name="Weisblum_eLife"/>
 +
|-
 +
| G446V || Substantially decreases the neutralization titers of plasma<ref name="Greaney"/>
 +
|-
 +
| N450D || Results in antibody resistance<ref name="Cong_CellHM2021"/>
 +
|-
 +
| E484R/S || A site of mutation being reported in multiple variants, mutation at this site could harbor escape mutations that impede the binding and neutralization ability of antibodies<ref name=":0"/> <ref name="Greaney"/>
 +
|-
 +
| F490P || Mutation at this site enables antibody escape over mAb COV2-2479, COV2-2050, COV2-2096 based on DMS study.<ref name="Greaney"/>
 +
|-
 +
| S494P || This mutation persistently shows up in an immunocompromised patient of COVID-19, which was treated various drugs and antibodies e.g. remdesivir, intravenous immunoglobulin, etc.<ref name="Choi"/>
 +
|}
 +
 
 +
==CTDs==
 +
{| class="wikitable"
 +
|-
 +
! Outlined Mutations !! Conformation
 +
|-
 +
| T547I || Functional impact to be confirmed in future investigation.
 +
|-
 +
| T572I || Functional impact to be confirmed in future investigation.
 +
|-
 +
| D574V || Located at the CTD1 region, substitution to an electrically neutral valine residue permits the endosomal entry efficiency and immune evasion ability of SARS-CoV-2.<ref name="Zhou_CellHM2020"/>
 +
|-
 +
| E619Q || Functional impact to be confirmed in future investigation.
 +
|-
 +
| E658S || Functional impact to be confirmed in future investigation.
 +
|-
 +
| I666V || Functional impact to be confirmed in future investigation.
 +
|-
 +
| S673G || Functional impact to be confirmed in future investigation.
 +
|-
 +
| P681Y || Located at the C-terminal of the CTD2, this substitution can diminish the cleavage efficiency of the S1/S2 interface because the bulky nature of tyrosine hinders the binding of furin to the cleavage loop.<ref name="Henrich"/><ref name="Tian_2009"/></big>
 +
|-
 +
| I688V || Functional impact to be confirmed in future investigation.
 +
|}
 +
==S2==
 +
{| class="wikitable"
 +
|-
 +
! Outlined Mutations !! Conformation
 +
|-
 +
| D796H || Located in S2 region, the single aspartic acid-to-histidine substitution was found to enhance the neutralization resistance of the spike glycoprotein in a chronical infection patient.<ref name="KempCIP" /></big>
 +
|}
  
−
The omicron variant is notorious for having a large number of mutations, some of which are known to be involved in escaping various antibodies. The deLemus website has captured many of these mutations, one of which is F486V in BA.4 and BA.5. It has been reported in some research showing that this loss of phenylalanine in the RBD of the spike protein is in a lot of binding sites of monoclonal antibodies (mAbs). S704L, a reported novel mutation in BA.2.12.1 in the post-RBD region of the spike, has also been captured by deLemus. The captured BA.2.75 mutations include K147E, I210V, and G257S, 3 mutations in the N-terminal domain (NTD), and N460K, an RBD mutation which is all reported. For BQ.1, deLemus captured a reported RBD mutation K444T. Two reported mutations, H146Q (NTD) and V445P (RBD), are detected by deLemus for XBB.<br /></big>
+
== References ==
 +
<references>
 +
<ref name="XBB.1.5">Yue, C. ''et al''. Enhanced transmissibility of XBB.1.5 is contributed by both strong ACE2 binding and antibody evasion. Preprint at https://www.biorxiv.org/content/10.1101/2023.01.03.522427v2 (2023).</ref>
 +
<ref name=":4">Cao, Y. ''et al.'' Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution. ''Nature'' (2022). DOI:10.1038/s41586-022-05644-7</ref>
 +
<ref name="Zahradník">Zahradník, J. ''et al.'' SARS-CoV-2 variant prediction and antiviral drug design are enabled by RBD in vitro evolution. ''Nat Microbiol'' '''6,''' 1188 (2021).</ref>
 +
<ref name="Makowski">Makowski, E. K., Schardt, J. S., Smith, M. D. & Tessier, P. M. Mutational analysis of SARS-CoV-2 variants of concern reveals key tradeoffs between receptor affinity and antibody escape. ''PLOS Comput Biol'' '''18,''' (2022).</ref>
 +
<ref name=":0">Qu, P. ''et al.'' Evasion of neutralizing antibody responses by the SARS-CoV-2 BA.2.75 variant. ''Cell Host Microbe'' '''30,''' 1518 (2022).</ref>
 +
<ref name=":2">Tamura, T. ''et al.'' Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two omicron subvariants. Preprint at https://www.biorxiv.org/content/10.1101/2022.12.27.521986v1 (2022).</ref>
 +
<ref name=":3">Wang, Q. ''et al.'' Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants. ''Cell'' '''186,''' 279 (2023).</ref>
 +
<ref name=":1">Qu, P. ''et al.'' Enhanced neutralization resistance of SARS-CoV-2 omicron subvariants BQ.1, BQ.1.1, BA.4.6, BF.7, and BA.2.75.2. ''Cell Host Microbe'' '''31,''' 9 (2023).</ref>
 +
<ref name="Tuekprakhon">Tuekprakhon, A. ''et al.'' Antibody escape of SARS-CoV-2 omicron BA.4 and BA.5 from Vaccine and BA.1 Serum. ''Cell'' '''185,''' 2422 (2022).</ref>
 +
<ref name="Wang">Wang, Q. ''et al.'' Antibody evasion by SARS-CoV-2 omicron subvariants BA.2.12.1, BA.4 and BA.5. ''Nature'' '''608,''' 603 (2022).</ref>
 +
</references>
  
−
==Newly Reported Mutations==
+
==Summary==
−
<big>In the last 6 months, 3 omicron sublineages have been announced as Variant of Interest (VoI), which are BA.2.75, BQ.1, and XBB. These variants bring new mutable sites that are very important for the virus to improve its fitness.<br /></big>
+
<tabs>
−
===N460K===
+
<tab name="NTD"><htmltag tagname="img" src="https://wiki.laviebay.hkust.edu.hk/deLemus/RESEARCH_TEAMS/images/PublishedPlot/NTD.png" alt="test for htmltag img" class="wikimg" style="display: block;width:70%;margin-left: auto;margin-right: auto;"></htmltag></tab>
−
<big>N460K mutation is first reported in B.2.75, which became prevalent by July 2022. The mutation from Asparagine(N) to Arginine(R) at site 460 can increase the hACE2-binding affinity with the background of BA.2 mutation in the deep mutational study(DMS). Moreover, this mutation also grants immune evasive capability over monoclonal antibodies(mAbs). Not only in BA.2.75, but this mutation also shows up in the subsequent VoIs (BQ.1 and XBB). deLemus already outlined this mutation by February 2022, much earlier before it became prevalent.<br /></big>
+
<tab name="RBD"><htmltag tagname="img" src="https://wiki.laviebay.hkust.edu.hk/deLemus/RESEARCH_TEAMS/images/PublishedPlot/RBD.png" alt="test for htmltag img" class="wikimg" style="display: block;width:70%;margin-left: auto;margin-right: auto;"></htmltag></tab>
 +
<tab name="CTDs"><htmltag tagname="img" src="https://wiki.laviebay.hkust.edu.hk/deLemus/RESEARCH_TEAMS/images/PublishedPlot/CTDs.png" alt="test for htmltag img" class="wikimg" style="display:block;width:70%;margin-left: auto;margin-right: auto;"></htmltag></tab>
 +
<tab name="S2"><htmltag tagname="img" src="https://wiki.laviebay.hkust.edu.hk/deLemus/RESEARCH_TEAMS/images/PublishedPlot/S2.png" alt="test for htmltag img" class="wikimg" style="display: block;width:70%;margin-left: auto;margin-right: auto;"></htmltag></tab>
 +
</tabs>
  
−
===F486V/S, K444T===
+
<htmltag tagname="img" src="https://wiki.laviebay.hkust.edu.hk/deLemus/RESEARCH_TEAMS/images/PublishedPlot/NTD.png" alt="test for htmltag img" class="wikimg" style="display: block;width:70%;margin-left: auto;margin-right: auto;"></htmltag>
−
<big>F486V mutation previously showed up in BA.4&5 lineage. This mutation also shows up in BQ.1 lineage and exhibits polymorphism in the XBB lineage, with the mutation from Phenylalanine to Serin (F486S). This mutation facilitates the escape from class I and II mAbs and the DMS study also reveals the same immune evasive potential over COV2-2832 mAb. deLemus outlines the mutation activity in this site by March 2022. The mutation K444T is reported in BQ.1 as well. This mutation has been reported to abrogate the 2X324-neutralizing activity with various amino acids. deLemus also outlined the mutation in this site by the end of 2021.<br /></big>
 
  
−
===R346T, R368I, and V445P===
+
<htmltag tagname="img" src="https://wiki.laviebay.hkust.edu.hk/deLemus/RESEARCH_TEAMS/images/PublishedPlot/RBD.png" alt="test for htmltag img" class="wikimg" style="display: block;width:70%;margin-left: auto;margin-right: auto;"></htmltag>
−
<big>These three mutations have never been reported in the previous variants and currently, it shows up in the XBB variant. The mutation at site 346 was previously reported in the lambda variant, but with the amino acid Lysin(R346K) instead of Threonine(R346T) as in XBB. deLemus detected the mutation activity in this site by the end of 2021, which persistently exhibits high signal ever since. For site V445, deLemus also has detected the mutation signal in this site since April 2022. The DMS study reported an escape capability of this site over mAbs COV2-2449.<br /></big>
 
  
−
==Outlined Mutations==
+
<htmltag tagname="img" src="https://wiki.laviebay.hkust.edu.hk/deLemus/RESEARCH_TEAMS/images/PublishedPlot/CTDs.png" alt="test for htmltag img" class="wikimg" style="display:block;width:70%;margin-left: auto;margin-right: auto;"></htmltag>
−
<big>In addition, deLemus can reveal emerging sites that could potentially appear in future variants. By tracking and evaluating the mutation activity in the virus from the beginning of the pandemic, we have identified sites in different domains of the spike protein.<br /></big>
 
  
−
===K356T===
+
<htmltag tagname="img" src="https://wiki.laviebay.hkust.edu.hk/deLemus/RESEARCH_TEAMS/images/PublishedPlot/S2.png" alt="test for htmltag img" class="wikimg" style="display: block;width:70%;margin-left: auto;margin-right: auto;"></htmltag>
−
<big>Among all the detected mutations in spikes protein, this site is worthy to be monitored due to its persistent signal since April 2022. The mutation from Lysin(K) to Threonine(T) at site 356 enables N-X-T sequon, which is crucial for glycosylation, a defense mechanism for the virus to hide from immune surveillance, e.g., antibodies. Moreover, the emerging variant provided by GISAID also reveals that the R356T mutation shows up in the top 5 accelerating variants, the BN.1.4 variant.<br /></big>
 
  
 +
== '''Deep Mutational Scanning Data''' ==
 +
<big>The RBD-ACE2 binding data</big><ref>Greaney AJ, Starr TN, Gilchuk P, Zost SJ, Binshtein E, Loes AN, Hilton SK, Huddleston J, Eguia R, Crawford KHD, Dingens AS, Nargi RS, Sutton RE, Suryadevara N, Rothlauf PW, Liu Z, Whelan SPJ, Carnahan RH, Crowe JE Jr, Bloom JD. Complete Mapping of Mutations to the SARS-CoV-2 Spike Receptor-Binding Domain that Escape Antibody Recognition. Cell Host Microbe. 2021 Jan 13;29(1):44-57.e9. doi: 10.1016/j.chom.2020.11.007. Epub 2020 Nov 19. PMID: 33259788; PMCID: PMC7676316.</ref> <big>showed that R346S, N354S, E484R and S494P are the mutations lead to increased binding affinity in all the 5 background sequence.</big>
 +
{| class="wikitable"
 +
|+
 +
RBD-ACE2 binding affinity
 +
|'''Unique  Mutations'''
 +
|'''Date'''
 +
|'''Wuhan'''
 +
|'''Alpha'''
 +
|'''Beta'''
 +
|'''Eta'''
 +
|'''Delta'''
 +
|-
 +
|'''R346S'''
 +
|2023.01
 +
|0.12
 +
|0.14
 +
|0.07
 +
|0.03
 +
|0.11
 +
|-
 +
|'''N354S'''
 +
|2023.05
 +
|0.03
 +
|0.01
 +
|0.04
 +
|0.32
 +
|0.02
 +
|-
 +
|'''E484R'''
 +
|2023.01
 +
|0.06
 +
|0.04
 +
|  -
 +
|  -
 +
|0.11
 +
|-
 +
|'''S494P'''
 +
|2023.01
 +
|0.33
 +
|0.18
 +
|0.13
 +
|0.14
 +
|0.06
 +
|}
 +
<big>Immune escape data</big><ref>Tyler N. Starr., et al., Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution.''Science''377,420-424(2022).DOI:10.1126/science.abo7896</ref> <big>shows that the escape ability of R346S, V445A, G446I, and E484R against certain antibodies exceeds 90% mutations.</big>
 +
{| class="wikitable"
 +
|+
 +
Immune Escaping
 +
|'''Unique  Mutations'''
 +
|'''Date'''
 +
|'''Antybody1'''
 +
|'''Antybody2'''
 +
|'''Antybody3'''
 +
|'''Antybody4'''
 +
|'''Antybody5'''
 +
|-
 +
|'''R346S'''
 +
|2023.01
 +
|COV2-2082
 +
|COV2-2096
 +
|COV2-2479
 +
|COV2-2832
 +
|
 +
|-
 +
|'''V445A'''
 +
|2023.01
 +
|COV2-2050
 +
|COV2-2094
 +
|COV2-2479
 +
|COV2-2499
 +
|COV2-2677
 +
|-
 +
|'''G446I'''
 +
|2023.05
 +
|COV2-2096
 +
|COV2-2479
 +
|COV2-2499
 +
|
 +
|
 +
|-
 +
|'''E484R'''
 +
|2023.01
 +
|COV2-2050
 +
|COV2-2096
 +
|COV2-2479
 +
|COV2-2832
 +
|
 +
|}
 +
<big>Overall, by the first half of this year, '''R346S''' and '''E484R''' are the most potential dangerous mutations we captured.</big>
 +
-->
  
−
='''<big>Monthly Leading Sites</big>'''=
+
==References==
−
TEMP
+
<references>
 +
<ref name="Del Rio">Rössler, A. ''et al''. BA.2 and BA.5 Omicron Differ Immunologically from Both BA.1 Omicron and Pre-Omicron Variants. ''Nat Commun'' '''13''', 7701 (2022)</ref>
 +
<ref name="European Centre">Qu, P. ''et al''. Enhanced Neutralization Resistance of SARS-CoV-2 Omicron Subvariants BQ.1, BQ.1.1, BA.4.6, BF.7, and BA.2.75.2. ''Cell Host Microbe'' '''31''', 9 (2023)</ref>
 +
<ref name="Jackson2021">Jackson, C. B., Farzan, M., Chen, B. & Choe, H. Mechanisms of SARS-CoV-2 entry into cells. ''Nat Rev Mol Cell Biol'' '''23,''' 3 (2021).</ref>
 +
<ref name="Karim">Karim, S. S. A. & Karim, Q. A. Omicron SARS-CoV-2 variant: A new chapter in the COVID-19 pandemic. ''Lancet'' '''398,''' 2126 (2021).</ref>
 +
<ref name="Wang">Wang, Q. ''et al.'' Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants. ''Cell'' '''186,''' 279 (2023).</ref>
 +
<ref name="deLemus">deLemus team, Analysis of Leading Mutations in SARS-CoV-2 Spike Glycoproteins (in preparation, 2023).</ref>
 +
<ref name="GISAID">GISAID https://gisaid.org/</ref>
 +
<ref name="Cov-Lineages">Cov-Lineages https://cov-lineages.org/</ref>
 +
</references>
  
−
='''<big>Leading Mutation Map</big>'''=
 
−
TEMP
 
  
−
='''<big>Variant Distribution</big>'''=
+
<html><a href="https://www.revolvermaps.com/livestats/locations/57gzazn1dbb/"><img src="//rf.revolvermaps.com/h/m/a/0/ff0000/128/0/57gzazn1dbb.png" width="180" height="120" alt="Map" style="border:0;"></a></html>
−
TEMP
+
<html>
 +
<div id="sfc9pt5d2hy2d328lsrbbs6nlkm4sax62ug"></div>
 +
<script type="text/javascript" src="https://counter10.optistats.ovh/private/counter.js?c=9pt5d2hy2d328lsrbbs6nlkm4sax62ug&down=async" async></script>
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<noscript><a href="https://www.freecounterstat.com" title="free website counter"><img src="https://counter10.optistats.ovh/private/freecounterstat.php?c=9pt5d2hy2d328lsrbbs6nlkm4sax62ug" border="0" title="free website counter" alt="free website counter"></a></noscript>
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</html>
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[[Category:deLemus]]

Latest revision as of 10:25, 15 December 2023

Dynamic Expedition of Leading Mutations in SARS-CoV-2 Spike Glycoproteins


The dynamic epidemiology of coronavirus disease 2019 (COVID-19) since its outbreak has been a result of the continuous evolution of its etiological agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Within the first 2 years of this pandemic, the World Health Organization (WHO) has already announced 4 variants of concern (VOC), namely alpha (B.1.1.7), beta (B.1.351), gamma (P.1), and delta (B.1.617.2), together with numerous variants of interest (VOI). The latest lineage to be designated a VOC would be omicron (B.1.1.529),[1] from which a diverse variant soup is generated.[2] From the original BA.1 strain of November 2021 to the most recent XBB and BQ.1 strains of late 2022,[3][4] each omicron subvariant has successively proliferated and outcompeted its once dominant antecedent.[5] The emergence of all these variants has brought along many novel mutations that continue to fine-tune the fitness of the virus,[6][7] leading to its persistent global circulation. Recent emerging variant (EV) data retrieved from GISAID, as of 17 January 2023, has revealed that the top 4 most rapidly spreading lineages are the BA.1.1.22, CH.1.1, XBB.1.5, and BQ.1.1 variants, among which XBB.1.5 has been found to be especially prevalent in the US,[8] making up of more than 40% of its sequence coverage in early January 2023.

Spike Glycoprotein

The spike glycoprotein of SARS-CoV-2 is a trimeric type I viral fusion protein that binds the virus to the angiotensin-converting enzyme 2 (ACE2) receptor of a host cell.[9] It is composed of 2 subunits: the N-terminal subunit 1 (S1) and C-terminal subunit 2 (S2), within which multiple domains lie. The S1 region facilitates ACE2 binding and is made up of an N-terminal domain (NTD), a receptor-binding domain (RBD), and 2 C-terminal subdomains (CTD1 and CTD2), while the downstream S2 region is responsible for mediating virus-host cell membrane fusion.

Update

The identified leading mutations in 2023 are listed as follows [10]:

2023.12.01-2023.12.17

Outlined Mutations Confirmed in VOC/Emerging Variants
L455F EG.5.1.1
A475V EG.5.1.1
E654K HK.3

2023.11.01-2023.11.17

Outlined Mutations Confirmed in VOC/Emerging Variants
N185D HK.3.2
L455F EG.5.1.1
A475V JF.1
T572I FY.2
Q613H XBB.1.16
D1153Y HK.3

2023.10.06

Outlined Mutations Confirmed in VOC/Emerging Variants
L455F EG.5.1.1
A475V GK.1

2023.09.08-2023.09.28

Outlined Mutations Confirmed in VOC/Emerging Variants
R403K BA.2.86 (Pirola)
L455F EG.5.1.1
S494P EG.5.1.1
P521S XBB.1.16.15
E554K BA.2.86 (Pirola) & FE.1
Q613H BA.2.86 (Pirola)
P621S BA.2.86 (Pirola)
T732I XBB.2.3 x XBB.1.5
S939F BA.2.86 (Pirola)
V1264L CK.1.1

Here are the recently confirmed leading mutations.

2023.08.04 - 2023.08.22

Outlined Mutations Confirmed in VOC/Emerging Variants
N185D XBB.1.5
L212S FY.4.2
V445A XBC.1.6
L455F EG.5.1.1
F456L EG.5.1 (Eris)
E554Q XBB.1.5.18
Q613H XBB.1.16
T883I XBB.1.16

*The reported mutations of detected variants are from Cov-Lineages[11]

RBD Mutation Profile of Latest VOIs.

  • Generated 3D structure of spike protein with highlighted leading mutations (AlphaFold2, colab version 2022).

Here are the recently confirmed leading mutations.

2023.06.30 - 2023.07.05

Outlined Mutations Confirmed in VOC/Emerging Variants
H146K FL.2.3 (XBB.1.9.1.2.3)
S446N FL.19
F456L XBF


  • Generated 3D structure of spike protein with highlighted leading mutations (AlphaFold2, colab version 2022).

Here are the recently confirmed leading mutations.

2023.06.01 - 2023.06.13

Outlined Mutations Confirmed in VOC/Emerging Variants
F490P XBB.1.9.1
E554K XBB.1.9.1 (sublineage)
Q675K XBB.1.22.1
L858I CH.1.1.1


  • Generated 3D structure of spike protein with highlighted leading mutations (AlphaFold2, colab version 2022).

Here are the recently confirmed leading mutations.

2023.05.01 - 2023.05.12

Outlined Mutations Confirmed in VOC/Emerging Variants
F456L FD.1.1 & EG.5.1 (2023.08)
S494P XBB.2.3 & XBB.1.1
T572I FY.1 ( XBB.1.22.1.1 )

*The reported mutations of detected variants are from GISAID


  • Generated 3D structure of spike protein with highlighted leading mutations (AlphaFold2, colab version 2022).

Here are the recently confirmed leading mutations.

2023.04.01 - 2023.04.21

Outlined Mutations Confirmed in VOC/Emerging Variants
H146K XBB.1.5 & XBB.1.16
M153I XBB.2.3.3
E180V XBB.1.16
K444R XBB.1.5
T478R XBB.1.16, XBB.1.5, CH.1.1.2 & XBB.2.3
F490P XBB.2.6
S494P XBB.1.5
Q613H XBB.1.16
P621S XBB.2.3
A688V XAY.1.1.1

  • Generated 3D structure of spike protein with highlighted leading mutations (AlphaFold2, colab version 2022).

Here are the recently confirmed leading mutations.

2023.03.01 - 2023.03.21

Outlined Mutations Confirmed in VOC/Emerging Variants
Y248S BQ.1
F490P XBB.1 & XBB.1.5
T547I XBB.1.16
Q613H DV.1, CH.1.1.1 & CH.1.1.17
I666V XBB.1.5
V1264L CH.1.1

  • Generated 3D structure of spike protein with highlighted leading mutations (AlphaFold2, colab version 2022).

Here are the recently confirmed leading mutations.

2023.02.03 - 2023.02.20

Outlined Mutations Confirmed in VOC/Emerging Variants
K147I XBB.1.5.2.1
Y248S BQ.1.1.43
S494P XBB.1.5
Q613H XBB.1.9.2 & XBB.2.4
P612S XBF
T678I BA.2.75 x BA.5
N679R CH.1.1
P1162S XBK.1

*The reported mutations of detected variants are from GISAID[12]

  • Generated 3D structure of spike protein with highlighted leading mutations (AlphaFold2, colab version 2022).

Here are the recently confirmed leading mutations.

2023.01.31

Outlined Mutations Confirmed in VOC/Emerging Variants
V445A BQ.1.1
T883I BQ.1.1

2023.01.17 - 2023.01.25

Outlined Mutations Confirmed in VOC/Emerging Variants
H146- / H146K BQ.1.1 / XBB.1.5
F486A BQ.1.1
E583D BQ.1.1
Q613H BQ.1.1
S939F BQ.1.1


References

  1. ↑ Karim, S. S. A. & Karim, Q. A. Omicron SARS-CoV-2 variant: A new chapter in the COVID-19 pandemic. Lancet 398, 2126 (2021).
  2. ↑ Callaway, E. COVID ‘variant soup’ is making winter surges hard to predict. Nature 611, 213 (2022).
  3. ↑ Wang, Q. et al. Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants. Cell 186, 279 (2023).
  4. ↑ Qu, P. et al. Enhanced Neutralization Resistance of SARS-CoV-2 Omicron Subvariants BQ.1, BQ.1.1, BA.4.6, BF.7, and BA.2.75.2. Cell Host Microbe 31, 9 (2023)
  5. ↑ Rössler, A. et al. BA.2 and BA.5 Omicron Differ Immunologically from Both BA.1 Omicron and Pre-Omicron Variants. Nat Commun 13, 7701 (2022)
  6. ↑ Carabelli, A. M. et al. SARS-CoV-2 variant biology: Immune escape, transmission and fitness. Nat Rev Microbiol (2023). DOI: https://doi.org/10.1038/s41579-022-00841-7.
  7. ↑ Witte, L. et al. Epistasis lowers the genetic barrier to SARS-CoV-2 neutralizing antibody escape. Nat Commun 14, 302 (2023).
  8. ↑ Callaway, E. Coronavirus variant XBB.1.5 rises in the United States — is it a global threat? Nature 613, 222 (2023).
  9. ↑ Jackson, C. B., Farzan, M., Chen, B. & Choe, H. Mechanisms of SARS-CoV-2 entry into cells. Nat Rev Mol Cell Biol 23, 3 (2021).
  10. ↑ deLemus team, Analysis of Leading Mutations in SARS-CoV-2 Spike Glycoproteins (in preparation, 2023).
  11. ↑ Cov-Lineages https://cov-lineages.org/
  12. ↑ GISAID https://gisaid.org/


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