deLemus

From
Revision as of 14:37, 8 February 2023 by Admin (talk | contribs)
Jump to navigation Jump to search

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


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.[9]

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.[10] 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 ~ 1 – 325), a 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.

Update (03/02/2023)

The identified leading mutations are listed as follows Cite error: Closing </ref> missing for <ref> tag |- |G257D |Located in the supersite loop of the NTD antigenic supersite for antibodies SLS28 and S2X333[11][12] ; Caused a gain of negative charge |- |A262S |Enhance the utilization of ACE2 in numerous mammals[13] ; May increase interspecies and intraspecies transmissibility |}

RBD

Outlined Mutations Conformation
R346I/S Possibly lead to immune evasion due to the disruption of class 3 antibodies binding site[14] [15]
K444N/R Escape mutations for covalescent plasma[16]
G446V Substantially decreases the neutralization titers of plasma[17]
N450D Results in antibody resistance[18]
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[19] [17]
F490P Mutation at this site enables antibody escape over mAb COV2-2479, COV2-2050, COV2-2096 based on DMS study.[17]
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.[20]

CTDs

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.[21]
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.[22][23]
I688V Functional impact to be confirmed in future investigation.

S2

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.[24]

-->

Summary

References

  1. ↑ Karim, S. S. A. & Karim, Q. A. Omicron SARS-CoV-2 variant: A new chapter in the COVID-19 pandemic. Lancet 398, 2126–2128 (2021).
  2. ↑ Callaway, E. COVID ‘variant soup’ is making winter surges hard to predict. Nature 611, 213–214 (2022).
  3. ↑ Wang, Q. et al. Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants. Cell 186, (2023).
  4. ↑ 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).
  5. ↑ Del Rio, C. & Malani, P. N. COVID-19 in 2022 - The Beginning of the End or the End of the Beginning? JAMA 327, 2389–2390 (2022).
  6. ↑ Carabelli, A. M. et al. SARS-CoV-2 variant biology: Immune escape, transmission and fitness. Nat Rev Microbiol (2023).
  7. ↑ Witte, L. et al. Epistasis lowers the genetic barrier to SARS-CoV-2 neutralizing antibody escape. Nat Commun 14, (2023).
  8. ↑ Callaway, E. Coronavirus variant XBB.1.5 rises in the United States — is it a global threat? Nature 613, 222–223 (2023).
  9. ↑ 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).
  10. ↑ Jackson, C. B., Farzan, M., Chen, B. & Choe, H. Mechanisms of SARS-CoV-2 entry into cells. Nat Rev Mol Cell Biol 23, 3–20 (2021).
  11. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named :4
  12. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named :3
  13. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named Wang_JMedVirol2022
  14. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named Gaebler
  15. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named WangQ_LancetID2022
  16. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named Weisblum_eLife
  17. ↑ 17.0 17.1 17.2 Cite error: Invalid <ref> tag; no text was provided for refs named Greaney
  18. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named Cong_CellHM2021
  19. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named :0
  20. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named Choi
  21. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named Zhou_CellHM2020
  22. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named Henrich
  23. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named Tian_2009
  24. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named KempCIP

Cite error: <ref> tag with name "deLemus" defined in <references> is not used in prior text.


Map

Retrieved from "https://wiki.laviebay.hkust.edu.hk/deLemus/index.php?title=deLemus&oldid=1591"