Difference between revisions of "deLemus"

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== '''Deep Mutational Scanning Data''' ==
 
== '''Deep Mutational Scanning Data''' ==
 +
The RBD-ACE2 binding data showed that R346S, N354S, E484R and S494P are the mutations lead to increased binding affinity in all the 5 background sequence.
 
{| class="wikitable"
 
{| class="wikitable"
 
|+
 
|+
 
RBD-ACE2 binding affinity
 
RBD-ACE2 binding affinity
 
|'''Unique  Mutations'''
 
|'''Unique  Mutations'''
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|Date
 
|'''Wuhan'''
 
|'''Wuhan'''
 
|'''Alpha'''
 
|'''Alpha'''
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|-
 
|-
 
|'''R346S'''
 
|'''R346S'''
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|0.12
 
|0.12
 
|0.14
 
|0.14
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|0.03
 
|0.03
 
|0.11
 
|0.11
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|-
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|'''N354S'''
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|
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|0.03
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|0.01
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|0.04
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|0.32
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|0.02
 
|-
 
|-
 
|'''E484R'''
 
|'''E484R'''
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|0.06
 
|0.06
 
|0.04
 
|0.04
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|-
 
|'''S494P'''
 
|'''S494P'''
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|
 
|0.33
 
|0.33
 
|0.18
 
|0.18
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|0.14
 
|0.14
 
|0.06
 
|0.06
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|}
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{| class="wikitable"
 +
|+
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|'''Unique  Mutations'''
 +
|Date
 +
|'''Antybody1'''
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|'''Antybody2'''
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|'''Antybody3'''
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|'''Antybody4'''
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|'''Antybody5'''
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|-
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|'''R346S'''
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|
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|COV2-2082
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|COV2-2096
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|COV2-2479
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|COV2-2832
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|
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|-
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|'''V445A'''
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|
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|COV2-2050
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|COV2-2094
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|COV2-2479
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|COV2-2499
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|COV2-2677
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|-
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|'''G446I'''
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|
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|COV2-2096
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|COV2-2479
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|COV2-2499
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|
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|
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|-
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|'''E484R'''
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|
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|COV2-2050
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|COV2-2096
 +
|COV2-2479
 +
|COV2-2832
 +
|
 
|}
 
|}
  

Revision as of 14:52, 19 May 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]:

  • 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

*The reported mutations of detected variants are from GISAID[11]


  • 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

*The reported mutations of detected variants are from Cov-Lineages[12]

  • 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

  • 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


Deep Mutational Scanning Data

The RBD-ACE2 binding data showed that R346S, N354S, E484R and S494P are the mutations lead to increased binding affinity in all the 5 background sequence.

RBD-ACE2 binding affinity
Unique Mutations Date Wuhan Alpha Beta Eta Delta
R346S 0.12 0.14 0.07 0.03 0.11
N354S 0.03 0.01 0.04 0.32 0.02
E484R 0.06 0.04 - - 0.11
S494P 0.33 0.18 0.13 0.14 0.06
Unique Mutations Date Antybody1 Antybody2 Antybody3 Antybody4 Antybody5
R346S COV2-2082 COV2-2096 COV2-2479 COV2-2832
V445A COV2-2050 COV2-2094 COV2-2479 COV2-2499 COV2-2677
G446I COV2-2096 COV2-2479 COV2-2499
E484R COV2-2050 COV2-2096 COV2-2479 COV2-2832

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. ↑ GISAID https://gisaid.org/
  12. ↑ Cov-Lineages https://cov-lineages.org/


Map

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