Connect with us

Health

The Omicron spike N679K mutation functions as a loss-of-function mutation that attenuates SARS-CoV-2 in vitro and in vivo

The Omicron spike N679K mutation functions as a loss-of-function mutation that attenuates SARS-CoV-2 in vitro and in vivo

 


In a recent study published in Bio Rxiv*In a preprint server, researchers discovered that loss-of-function mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant spike protein.

Study: Omicron variant loss-of-function mutation reduces spike protein expression and mitigates SARS-CoV-2 infection. Image Credit: JuanGaertner/Shutterstock.comstudy: Loss-of-function mutations in Omicron variants reduce spike protein expression and attenuate SARS-CoV-2 infection. Image Credit: JuanGaertner/Shutterstock.com

*Important Notices: Bio Rxiv We publish a non-peer-reviewed, preliminary scientific report and should not be taken as conclusive, to guide clinical practice/health-related actions, or to be treated as established information.

Background

Since the beginning of the 2019 coronavirus disease (COVID-19) pandemic, several concerned SARS-CoV-2 variants (VOCs) have emerged with different spike protein mutations.

The spike (S) protein on virions is composed of three subunits known as trimers. These subunits are called S1 and S2. Omicron’s research is primarily focused on the receptor binding domain (RBD) and its impact on infection or vaccine-induced immunity due to the numerous mutations present in the spike protein.

Mutations near the S1/S2 and furin cleavage sites (FCS) are known to contribute to the evolution of SARS-CoV-2, but their effects on omicron have not been extensively studied.

About research

In this study, researchers evaluated how the Omicron C-terminus of the SARS-CoV-2 S1 subunit (CTS1) mutation affects SARS-CoV-2 pathogenesis and transmission.

A mutant SARS-CoV-2 with N679K, P681H, and H655Y mutations was created in the WA1 backbone (YKH). We evaluated spiking in purified virions from wild-type (WT) and YKH infections. The team hypothesized that N679K could influence SARS-CoV-2 infection.

To assess this, a SARS-CoV-2 mutant with only the N679K mutation in the WA1 backbone was created. In this study, a 3- to 4-week-old golden Syrian hamster was infected with her N679K and observed for weight loss and disease progression over a 7-day period.

The team identified the cause behind the loss of function seen in the N679K mutant. Given that N679K is located next to his FCS, we assessed the effect of his N679K on proteolytic spike processing. Spiking was examined by blotting purified virions from N679K, WT, and Omicron variant BA.1.

result

The YKH mutant produced smaller plaques than the WT strain. The YKH mutant showed no reduced stock titer or replication rate in Vero E6 cells compared to the SARS-CoV-2 WT strain.

YKH-associated endpoint titers were higher at 48 hours post-infection (hpi) of Calu-3 2B4 cells compared to WT, but replication was reduced at 24 hpi. This study shows that the three mutations affect the infection dynamics of her Omicron subspecies and may provide some benefit.

The YKH spike protein, like Omicron and Delta, received more processing than the WT spike protein. At 24 hpi, the ratio of S1/S2 cleavage ratio to full-length spike ratio in YKH spikes was approximately 2.4:1, whereas WT had similar levels of S1/S2 products as full-length.

YKH mutants containing H655Y, N679K, and P681H mutations conferred higher viral endpoint yields in human respiratory cells and played a role in improving Omicron spiking.

N679K plaque sizes were smaller compared to WT at 2 and 3 days post-infection (dpi), and initial characterization indicated negligible stock titers. The observed variability in plaque size and stock titer is consistent with previous findings for most Omicron strains.

The N679K mutant showed reduced replication in Calu-3 2B4 and Vero E6 cells at 24 hpi, in contrast to the minimal differences observed in YKH replication kinetics. In this study, we found that N679K virus titers recovered by 48 hpi. This mutation appears to be a replication loss of function in both cell lines.

Hamsters infected with N679K lost less weight than hamsters infected with WT. This study found that her N679K virus titers detected in lung samples were similar to wild-type he at 2 and 4 days dpi despite significant weight loss.

At 2 dpi, the N679K mutant virus showed virus titers similar to wild-type virus in nasal washes. However, at 4 dpi, mutant virus showed reduced replication compared to wild-type virus.

This study suggests that the N679K mutation contains a loss-of-function phenotype both in vitro and in vivo. The researchers hypothesize that the effects of the P681H and H655Y mutations may mitigate this loss of function.

N679K exhibited a 66% lower signal-to-noise ratio than WT, indicating a greater reduction in spike protein compared to that in purified virions. In this study, we found that his S/N ratio in Omicron was similarly reduced, suggesting that the phenotype was consistent despite all mutations in Omicron. The N679K mutation results in lower levels of Omicron spike protein than WT.

Conclusion

The results of this study showed that the Omicron N679K mutation leads to consistent loss-of-function of subvariants. The N679K mutation reduces viral potency both in vitro and in vivo by promoting spike disassembly.

The amplifying effects of other Omicron mutations such as H655Y and P681H on spiking and infection may offset the weakening effect of the N679K mutation.

Downregulation of spike protein by N679K may affect immunity from vaccines and infections. Further studies are needed to clarify the critical impact of Omicron CTS1 mutations on SARS-CoV-2 infection.

*Important Notices: Bio Rxiv We publish a non-peer-reviewed, preliminary scientific report and should not be taken as conclusive, to guide clinical practice/health-related actions, or to be treated as established information.

Sources

1/ https://Google.com/

2/ https://www.news-medical.net/news/20230420/Omicron-spike-N679K-mutation-acts-as-a-loss-of-function-mutation-attenuating-SARS-CoV-2-in-vitro-in-vivo.aspx

The mention sources can contact us to remove/changing this article

What Are The Main Benefits Of Comparing Car Insurance Quotes Online

LOS ANGELES, CA / ACCESSWIRE / June 24, 2020, / Compare-autoinsurance.Org has launched a new blog post that presents the main benefits of comparing multiple car insurance quotes. For more info and free online quotes, please visit https://compare-autoinsurance.Org/the-advantages-of-comparing-prices-with-car-insurance-quotes-online/ The modern society has numerous technological advantages. One important advantage is the speed at which information is sent and received. With the help of the internet, the shopping habits of many persons have drastically changed. The car insurance industry hasn't remained untouched by these changes. On the internet, drivers can compare insurance prices and find out which sellers have the best offers. View photos The advantages of comparing online car insurance quotes are the following: Online quotes can be obtained from anywhere and at any time. Unlike physical insurance agencies, websites don't have a specific schedule and they are available at any time. Drivers that have busy working schedules, can compare quotes from anywhere and at any time, even at midnight. Multiple choices. Almost all insurance providers, no matter if they are well-known brands or just local insurers, have an online presence. Online quotes will allow policyholders the chance to discover multiple insurance companies and check their prices. Drivers are no longer required to get quotes from just a few known insurance companies. Also, local and regional insurers can provide lower insurance rates for the same services. Accurate insurance estimates. Online quotes can only be accurate if the customers provide accurate and real info about their car models and driving history. Lying about past driving incidents can make the price estimates to be lower, but when dealing with an insurance company lying to them is useless. Usually, insurance companies will do research about a potential customer before granting him coverage. Online quotes can be sorted easily. Although drivers are recommended to not choose a policy just based on its price, drivers can easily sort quotes by insurance price. Using brokerage websites will allow drivers to get quotes from multiple insurers, thus making the comparison faster and easier. For additional info, money-saving tips, and free car insurance quotes, visit https://compare-autoinsurance.Org/ Compare-autoinsurance.Org is an online provider of life, home, health, and auto insurance quotes. This website is unique because it does not simply stick to one kind of insurance provider, but brings the clients the best deals from many different online insurance carriers. In this way, clients have access to offers from multiple carriers all in one place: this website. On this site, customers have access to quotes for insurance plans from various agencies, such as local or nationwide agencies, brand names insurance companies, etc. "Online quotes can easily help drivers obtain better car insurance deals. All they have to do is to complete an online form with accurate and real info, then compare prices", said Russell Rabichev, Marketing Director of Internet Marketing Company. CONTACT: Company Name: Internet Marketing CompanyPerson for contact Name: Gurgu CPhone Number: (818) 359-3898Email: [email protected]: https://compare-autoinsurance.Org/ SOURCE: Compare-autoinsurance.Org View source version on accesswire.Com:https://www.Accesswire.Com/595055/What-Are-The-Main-Benefits-Of-Comparing-Car-Insurance-Quotes-Online View photos

ExBUlletin

to request, modification Contact us at Here or [email protected]