Difference between revisions of "deLemus"

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__NOTOC__
 
__NOTOC__
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Dynamic Expedition of Leading Mutations in SARS-CoV-2 Spike Glycoprotein
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''Dynamic Expedition of Leading Mutations in SARS-CoV-2 Spike Glycoproteins''
  
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='''<big>Spike Glycoprotein</big>'''=
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</br>
−
The spike glycoprotein is a trimeric type I viral fusion protein that binds the virus to the angiotensin-converting enzyme 2 (ACE2) receptor on a host cell.  
+
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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 +
==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.
  
−
The spike glycoprotein per se is composed of 2 subunits:  
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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>
−
the N-terminal subunit 1 (S1) and
+
=='''Update'''==
−
C-terminal subunit 2 (S2),
+
The identified leading mutations in 2023 are listed as follows <ref name="deLemus" />:
−
within which multiple domains lie.
 
  
−
The S1 region facilitates ACE2 binding, and is made up of:
+
<tabs>
−
N-terminal domain (NTD ~ 1 – 325 ),
 
−
Receptor-binding domain (RBD ~ 326 – 525 ), and
 
−
2 C-terminal subdomains (CTD1 and CTD2 ~ 526 – 688 ),
 
−
while the downstream S2 region is responsible for mediating virus-host cell membrane fusion.
 
  
 +
<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>
  
−
='''<big>Update (30/12/2022)</big>'''=
+
===2023.12.01-2023.12.17===
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<html><iframe width="1180" height="570" src="https://docs.google.com/spreadsheets/d/e/2PACX-1vT6heuYwqnms3FjO2IgXcJjcmk3vCTm6o4ZQvzpa7pM83sc3212WE48M2q-1TmZXSv3YScW7YonpiQO/pubhtml?gid=278397406&single=true"></iframe></html>
+
{| 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>
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 +
<tab name="2023.07">
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<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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 +
* 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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 +
* 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>
 +
* 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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 +
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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>
 +
 
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 +
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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>
 +
 
 +
===2023.01.31===
 +
{| 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>
 +
|}
 +
 
 +
== 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>
  
 
==Summary==
 
==Summary==
−
<big>Since the outbreak of COVID-19, there have been new variants emerging. In the first 2 years of the pandemic, WHO has announced 4 Variant of Concern (VOC) so far, namely alpha(B.1.1.7), beta(B.1.351), gamma(P.1), delta(B.1.617.2). Omicron, the latest lineage designated as a VOC by the WHO after being reported in South Africa in November 2021,<ref name="Karim"/> has various subvariants, including BA.1 (the first subvariant of omicron), BA.2,<ref name="Arora"/> BA.4, and BA.5.<ref name="Tegally"/> 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.<ref name="Yamasoba"/> 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.<ref name="Tegally"/> These two variants became dominant in the UK and the US in June 2022.<ref name="Callaway"/> In the meantime, BA.2.12.1 and BA.2.75 were also spreading in the US and India respectively in May 2022.<ref name="Del Rio"/><ref name="Shaheen"/> In August 2022, XBB, which is a recombinant of BA.2.10.1 and BA.2.75, was found to have a small outbreak in various countries such as Singapore.<ref name="Wang"/> After that, in October 2022, BQ.1, which is a subvariant of BA.5 starting to prevail in France, was found.<ref name="European Centre"/> deLemus can highlight the leading mutation in spikes glycoprotein of SARS-CoV-2. The leading mutations of deLemus not only capture the mutation signal from reported variants but also other mutations that potentially show up in the next variant.
+
<tabs>
−
<br /></big>
+
<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>
 +
<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>
  
−
===K356T ===
+
<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>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>
 
  
−
===F486P/I ===
+
<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>The next mutation is F486P/I. Mutation from Phenylalanine (F) to Proline (P) at site 486 shows up in the recent accelerated variant, XBB.1.5, which is currently showing substantial growth in the US.<ref name="CNBC XBB.1.5"/> This mutation renders higher hACE2-binding affinity compared to its ancestor (XBB.1), that is likely responsible for its high growth.<ref name="XBB.1.5"/> We also noticed another leading mutation on the same site, F486I, which could be a dangerous mutation in the coming time.<br /></big>
 
  
 +
<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>Other than confirmed mutation as described above, deLemus also highlight several leading mutations in spike glycoprotein. These mutations haven't been mentioned or reported in the circulating variant which is worth to be monitored further.<br /></big>
+
<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>
  
−
===R346S/I ===
+
== '''Deep Mutational Scanning Data''' ==
−
R346S, a potential mutation predicted by deLemus, was shown to be involved in the immune escape from the monoclonal antibody S309, a precursor of sotrovimab, in an in vitro experiment. This mutation locates on the epitope of the antibody. After treating the infected cells with S309, R346S (together with P337L) showed up in the spike protein of the virus, substantially lowering its affinity to the antibody without affecting its binding to ACE2.<ref>Magnus. et al. Targeted Escape of SARS-CoV-2 in Vitro from Monoclonal Antibody S309, the Precursor of Sotrovimab. Front Immunol. 13, 966236 (2022).</ref>
+
<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"
−
===V445A ===
+
|+
−
TEMP
+
RBD-ACE2 binding affinity
−
===N450D ===
+
|'''Unique  Mutations'''
−
TEMP
+
|'''Date'''
−
===E484R/S ===
+
|'''Wuhan'''
−
TEMP
+
|'''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>
 +
-->
  
 
==References==
 
==References==
 
<references>
 
<references>
−
<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, 2126–2128 (2021).</ref>
+
<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="Arora">Arora, P. et al. Comparable neutralisation evasion of SARS-CoV-2 omicron subvariants BA.1, BA.2, and BA.3. Lancet Infect. Dis. 22, 766–767 (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="Tegally">Tegally, H. et al. Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa. Nat. Med. 28, 1785–1790 (2022).</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="Yamasoba">Yamasoba, D. et al. Virological characteristics of the SARS-CoV-2 Omicron BA.2 spike. Cell 185, 2103-2115.e19 (2022).</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="Callaway">Callaway, E. What Omicron’s BA.4 and BA.5 variants mean for the pandemic. Nature 606, 848–849 (2022).</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="Del Rio">Del Rio, C. & Malani, P. N. COVID-19 in 2022 - The Beginning of the End or the End of the Beginning? JAMA - J. Am. Med. Assoc. 327, 2389–2390 (2022).</ref>
+
<ref name="deLemus">deLemus team, Analysis of Leading Mutations in SARS-CoV-2 Spike Glycoproteins (in preparation, 2023).</ref>
−
<ref name="Shaheen">Shaheen, N. et al. Could the New BA.2.75 Sub-Variant Cause the Emergence of a Global Epidemic of COVID-19? A Scoping Review. Infect. Drug Resist. 15, 6317–6330 (2022).</ref>
+
<ref name="GISAID">GISAID https://gisaid.org/</ref>
−
<ref name="Wang">Wang, Q. et al. Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants. Cell 1–8 (2022) doi:10.1016/j.cell.2022.12.018.</ref>
+
<ref name="Cov-Lineages">Cov-Lineages https://cov-lineages.org/</ref>
−
<ref name="European Centre">European Centre for Disease Prevention and Control: Spread of the SARS-CoV-2 Omicron variant sub-lineage BQ.1 in the EU/EEA https://www.ecdc.europa.eu/sites/default/files/documents/Epi-update-BQ1.pdf (2022).</ref>
 
−
<ref name="CNBC XBB.1.5">Highly immune evasive omicron XBB.1.5 variant is quickly becoming dominant in U.S. as it doubles weekly https://www.cnbc.com/2022/12/30/covid-news-omicron-xbbpoint1point5-is-highly-immune-evasive-and-binds-better-to-cells.html (2023).</ref>
 
−
<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. bioRxiv https://www.biorxiv.org/content/10.1101/2023.01.03.522427v1 (2023).</ref>
 
 
</references>
 
</references>
 +
  
 
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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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