The emergence of the Omicron variant has once again put the world on high alert, and for good reason. With over 50 mutations in its spike protein alone, the virus is causing concern among experts about its potential to evade immunity and cause severe disease. But amidst the worry, there may be a glimmer of hope. Recent research has revealed that one of the mutations present in Omicron, called N679K, may actually diminish the virus’s ability to infect cells. In this article, we’ll take a closer look at this intriguing discovery and what it could mean for our fight against COVID-19.
According to a recent study posted on the preprint server bioRxiv, a loss-of-function mutation in the SARS-CoV-2 Omicron variant reduces the expression of the spike protein and attenuates the virus’s infection. The spike protein on virions comprises three subunits, known as a trimer, and Omicron studies have mainly concentrated on the receptor-binding domain (RBD) and its effect on infection- or vaccine-induced immunity due to the numerous mutations present in the spike protein.
The research aimed to assess how the SARS-CoV-2 Omicron C-terminus of the S1 subunit (CTS1) mutations impact SARS-CoV-2 pathogenesis and infection. A mutant SARS-CoV-2 with N679K, P681H, and H655Y mutations was created in the WA1 backbone (YKH). The study involved infecting three to four weeks old golden Syrian hamsters with N679K and noting weight loss and disease progression for seven days.
The YKH mutant produced smaller plaques than the wild-type (WT) strain, but no reduction in stock titers or replication kinetics within Vero E6 cells compared to the SARS-CoV-2 WT strain. The study indicated that the three mutations might influence the Omicron variant’s infection dynamics, potentially providing some benefits. The YKH spike protein underwent more processing, similar to Omicron and Delta. The YKH mutant, which contains the H655Y, N679K, and P681H mutations, led to higher viral endpoint yields within human respiratory cells and played a role in the improved spike processing of Omicron.
The N679K mutation leads to a consistent loss of function in subvariants and reduced the virus’s strength both in vitro and in vivo by enhancing spike degradation. The amplifying effects of other Omicron mutations, such as H655Y and P681H on spike processing and infection may offset the N679K mutation’s weakening effect. The reduced spike protein expression caused by N679K could impact immunity resulting from vaccines and infection.
Further research is needed to clarify the significant impact of the Omicron CTS1 mutations on SARS-CoV-2 infection. It should be noted that bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive or guide clinical practice/health-related behavior or treated as established information.
Overall, the discovery of the N679K mutation within the Omicron variant of SARS-CoV-2 is a promising development for the ongoing fight against COVID-19. The mutation’s apparent loss-of-function effect on the virus means it may be less potent than previous variants. While further studies are necessary to fully understand the implications of the N679K mutation, there is hope that it could ultimately lead to milder cases of COVID-19 in infected individuals. As we continue to monitor the spread of COVID-19 and its many variants, the medical community will undoubtedly remain vigilant in its efforts to develop effective treatments and vaccines to combat this devastating disease.
