Difference between revisions of "deLemus"
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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. It is composed of 2 subunits: 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. | 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. It is composed of 2 subunits: 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. | ||
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Revision as of 10:58, 17 January 2023
Dynamic Expedition of Leading Mutations in SARS-CoV-2 Spike Glycoprotein
Spike Glycoprotein
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. It is composed of 2 subunits: 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.
Highlight
A new omicron sublineage, XBB.1.5, already surged up in the USA. This variant has shown significant growth since late December 2022.[1] Even though XBB.1.5 only harbor a single novel mutation, F486P, it is capable to enhance hACE2-binding up to 5-fold compared to its ancestor, XBB.1.[2] deLemus has captured this mutation since November 2022, together with other mutations in RBD (check figure below).
Update (30/12/2022)
Summary
Since the outbreak of COVID-19, there have been new variants emerging. In the first 2 years of the pandemic, WHO has announced many Variants of Concern (VOC) and Variants of Interest (VOI) 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,[3] has various subvariants.[4] 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.[5] In April 2022, BA.4 and BA.5 were monitored by the WHO after being found in multiple countries. They showed a significant increase in growth advantage when compared to BA.2.[4] These two variants became dominant in the UK and the US in June 2022.[6] In the meantime, BA.2.12.1 and BA.2.75 were also spreading in the US and India respectively in May 2022.[7][8] In August 2022, XBB, which is a recombinant of BA.2.10.1 and BA.2.75, was surged up in various countries as well.[9] After that, in October 2022, BQ.1, which is a subvariant of BA.5 starting to prevail in France, was found.[10] deLemus can highlight the leading mutation in spikes glycoprotein of SARS-CoV-2. The leading mutations of deLemus capture not only the mutation signal from reported variants but also other mutations that potentially show up in the next variant.
K356T
Among all the detected mutations in spikes protein, this site is worthy of being 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.
F486P/I
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.[11] This mutation renders higher hACE2-binding affinity compared to its ancestor (XBB.1), that is likely responsible for its high growth.[2] We also noticed another leading mutation on the same site, F486I, which could be a dangerous mutation in the coming time.
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.
R346S/I
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.[12]
N450D
N450D, the possible effects of which were not well studied in previous research, is a new potential mutation found by deLemus. This site was located at the β-sheet 1 (N450-F456) region, which was shown to be involved in the reinforcement of the binding between the spike protein and ACE2 in silico.[13]
References
- ↑ COVID Data Tracker: Variant Proportion https://covid.cdc.gov/covid-data-tracker/#variant-proportions (2023).
- ↑ 2.0 2.1 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).
- ↑ 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).
- ↑ 4.0 4.1 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).
- ↑ Yamasoba, D. et al. Virological characteristics of the SARS-CoV-2 Omicron BA.2 spike. Cell 185, 2103-2115.e19 (2022).
- ↑ Callaway, E. What Omicron’s BA.4 and BA.5 variants mean for the pandemic. Nature 606, 848–849 (2022).
- ↑ 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).
- ↑ 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).
- ↑ 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.
- ↑ 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).
- ↑ 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).
- ↑ Magnus. et al. Targeted Escape of SARS-CoV-2 in Vitro from Monoclonal Antibody S309, the Precursor of Sotrovimab. Front Immunol. 13, 966236 (2022).
- ↑ Cong, Y. et al. Anchor-Locker Binding Mechanism of the Coronavirus Spike Protein to Human ACE2: Insights from Computational Analysis. J Chem Inf Model. 61(7), 3529–3542 (2021).
