Difference between revisions of "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]:

2023.122023.112023.102023.092023.082023.072023.062023.052023.042023.032023.022023.01

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/

[Karim-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).

[Wang-3] Wang, Q. et al. Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants. Cell 186, 279 (2023).

[European_Centre-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)

[Del_Rio-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).

[Jackson2021-9] 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).

[deLemus-10] Lemus team, Analysis of Leading Mutations in SARS-CoV-2 Spike Glycoproteins (in preparation, 2023).

[Cov-Lineages-11] Cov-Lineages https://cov-lineages.org/

[GISAID-12] GISAID https://gisaid.org/

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[6]

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[11]

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+|-
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+|-
+! 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
+|-
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+|-
+! Outlined Mutations !! Confirmed in VOC/Emerging Variants
+|-
+| <span style="color:burlywood;">'''L455F'''</span> || EG.5.1.1
+|-
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+{| 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
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 <big>Here are the recently confirmed leading mutations.</big>
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Difference between revisions of "deLemus"

Latest revision as of 10:25, 15 December 2023

Spike Glycoprotein

Update

2023.12.01-2023.12.17

2023.11.01-2023.11.17

2023.10.06

2023.09.08-2023.09.28

2023.08.04 - 2023.08.22

RBD Mutation Profile of Latest VOIs.

2023.06.30 - 2023.07.05

2023.06.01 - 2023.06.13

2023.05.01 - 2023.05.12

2023.04.01 - 2023.04.21

2023.03.01 - 2023.03.21

2023.02.03 - 2023.02.20

2023.01.31

2023.01.17 - 2023.01.25

References

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