Difference between revisions of "deLemus"
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__NOTOC__ | __NOTOC__ | ||
''Dynamic Expedition of Leading Mutations in SARS-CoV-2 Spike Glycoproteins'' | ''Dynamic Expedition of Leading Mutations in SARS-CoV-2 Spike Glycoproteins'' | ||
| + | |||
</br> | </br> | ||
| − | |||
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. | 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. | ||
| − | + | <!-- | |
| + | --> | ||
==Spike Glycoprotein== | ==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 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. | ||
<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> | <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> | ||
| − | |||
=='''Update'''== | =='''Update'''== | ||
The identified leading mutations in 2023 are listed as follows <ref name="deLemus" />: | The identified leading mutations in 2023 are listed as follows <ref name="deLemus" />: | ||
<tabs> | <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> | ||
| + | |||
| + | </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> | ||
| + | <html> | ||
| + | <style> | ||
| + | .molstar { | ||
| + | position: relative; | ||
| + | width: 80%; | ||
| + | padding-bottom: 56.25%; | ||
| + | } | ||
| + | </style> | ||
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| + | |||
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| + | <script type="text/javascript"> | ||
| + | molstar.Viewer.create('viewer-7', { | ||
| + | layoutIsExpanded: false, | ||
| + | layoutShowControls: false, | ||
| + | layoutShowRemoteState: false, | ||
| + | layoutShowSequence: true, | ||
| + | layoutShowLog: false, | ||
| + | layoutShowLeftPanel: true, | ||
| + | |||
| + | viewportShowExpand: true, | ||
| + | viewportShowSelectionMode: false, | ||
| + | viewportShowAnimation: false, | ||
| + | }).then(viewer => { | ||
| + | viewer.loadSnapshotFromUrl('https://wiki.laviebay.hkust.edu.hk/deLemus/RESEARCH_TEAMS/pdb/LM_2023_07.molx', 'molx'); | ||
| + | }); | ||
| + | </script> | ||
| + | </html> | ||
| + | * Generated 3D structure of spike protein with highlighted leading mutations (AlphaFold2, colab version 2022). | ||
| + | |||
| + | <big>Here are the recently confirmed leading mutations.</big> | ||
| + | |||
| + | ===2023.06.30 - 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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| + | <style> | ||
| + | .molstar { | ||
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| + | width: 80%; | ||
| + | padding-bottom: 56.25%; | ||
| + | } | ||
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| + | <link rel="stylesheet" type="text/css" href="https://molstar.org/viewer/molstar.css" /> | ||
| + | <script type="text/javascript" src="https://molstar.org/viewer/molstar.js"></script> | ||
| + | |||
| + | <div id="viewer-6" class="molstar" style="display: block; margin-left:auto; margin-right:auto; padding-bottom: 40%;"></div> | ||
| + | <script type="text/javascript"> | ||
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| + | layoutIsExpanded: false, | ||
| + | layoutShowControls: false, | ||
| + | layoutShowRemoteState: false, | ||
| + | layoutShowSequence: true, | ||
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| + | |||
| + | viewportShowExpand: true, | ||
| + | viewportShowSelectionMode: false, | ||
| + | viewportShowAnimation: false, | ||
| + | }).then(viewer => { | ||
| + | viewer.loadSnapshotFromUrl('https://wiki.laviebay.hkust.edu.hk/deLemus/RESEARCH_TEAMS/pdb/LM_2023_06.molx', 'molx'); | ||
| + | }); | ||
| + | </script> | ||
| + | </html> | ||
| + | * Generated 3D structure of spike protein with highlighted leading mutations (AlphaFold2, colab version 2022). | ||
| + | |||
| + | <big>Here are the recently confirmed leading mutations.</big> | ||
| + | |||
| + | ===2023.06.01 - 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"> | <tab name="2023.05"> | ||
| Line 56: | Line 276: | ||
! Outlined Mutations !! Confirmed in VOC/Emerging Variants | ! Outlined Mutations !! Confirmed in VOC/Emerging Variants | ||
|- | |- | ||
| − | | <span style="color:burlywood;">'''F456L'''</span> || FD.1.1 | + | | <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 | + | ''*The reported mutations of detected variants are from GISAID'' |
| Line 123: | Line 347: | ||
| <span style="color:hotpink;">'''A688V'''</span> || XAY.1.1.1 | | <span style="color:hotpink;">'''A688V'''</span> || XAY.1.1.1 | ||
|} | |} | ||
| − | |||
</tab> | </tab> | ||
| Line 238: | Line 461: | ||
| <span style="color:cornflowerblue;">'''P1162S'''</span> || XBK.1 | | <span style="color:cornflowerblue;">'''P1162S'''</span> || XBK.1 | ||
|} | |} | ||
| + | ''*The reported mutations of detected variants are from GISAID<ref name="GISAID" />'' | ||
</tab> | </tab> | ||
| Line 437: | Line 661: | ||
<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> | <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> | ||
| − | + | ||
== '''Deep Mutational Scanning Data''' == | == '''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> | <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> | ||
| Line 528: | Line 752: | ||
|} | |} | ||
<big>Overall, by the first half of this year, '''R346S''' and '''E484R''' are the most potential dangerous mutations we captured.</big> | <big>Overall, by the first half of this year, '''R346S''' and '''E484R''' are the most potential dangerous mutations we captured.</big> | ||
| + | --> | ||
==References== | ==References== | ||
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
- ↑ Karim, S. S. A. & Karim, Q. A. Omicron SARS-CoV-2 variant: A new chapter in the COVID-19 pandemic. Lancet 398, 2126 (2021).
- ↑ Callaway, E. COVID ‘variant soup’ is making winter surges hard to predict. Nature 611, 213 (2022).
- ↑ Wang, Q. et al. Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants. Cell 186, 279 (2023).
- ↑ 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)
- ↑ 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)
- ↑ 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.
- ↑ Witte, L. et al. Epistasis lowers the genetic barrier to SARS-CoV-2 neutralizing antibody escape. Nat Commun 14, 302 (2023).
- ↑ Callaway, E. Coronavirus variant XBB.1.5 rises in the United States — is it a global threat? Nature 613, 222 (2023).
- ↑ 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).
- ↑ deLemus team, Analysis of Leading Mutations in SARS-CoV-2 Spike Glycoproteins (in preparation, 2023).
- ↑ Cov-Lineages https://cov-lineages.org/
- ↑ GISAID https://gisaid.org/
