Omicron-L452R could be the most risky SARS CoV-2 variant

April 11, 2022 0 By Krishna Unni

The Omicron-L452R – a recombinant variant of Omicron with a mutation of Delta that enhances the ability of Omicron to infect lung tissues- –  not only rescued fusogenicity but also strengthened infectivity, observes the latest study published on Nature.com.

Even as the Omicron variant of SARS CoV-2 exhibited diminished fusogenicity and pathogenicity compared with the Delta variant and the parental virus, a recent study investigating the effect of L452R, a mutation seen in the Delta variant, on the fusogenicity of the Omicron variant demonstrated that the combination (Omicron-L452R) exerted markedly enhanced fusogenicity and thereby it could be one of the most riskier variants.  This is because the essential role of the L452R mutation in SARS-CoV-2 was fusogenicity and infectivity. 

In the new study, the infectivity of the Omicron-L452R variant was investigated in K18-hACE2 transgenic mice in vivo. The bioluminescence of infected mice was measured to indicate the pseudovirus infection severity. Consistent with live SARS-CoV-2 virus, the Delta variant has the highest infectivity. The Omicron variant modestly inhibited infectivity, whereas Omicron-L452R significantly enhanced infectivity. qRT-PCR was performed to detect the infected pseudovirus copies. Compared to mice infected with the parental virus, the virus copies in the Omicron-infected mouse lung tissues were reduced, while the virus copies in the Omicron-L452R variant-infected mouse lung tissues were markedly enhanced. Therefore, the Omicron-L452R variant enhanced the ability of Omicron to infect lung tissues in vivo, reads the Nature article. 

While the Omicron variant is typically characterised as less pathogenic and more transmissible than the parental and previous variants, which may be due to crystal structure changes caused by over 30 mutations in the Spike protein, the researchers found in this investigation that the further mutation of L452R in the Omicron variant not only rescued fusogenicity but also strengthened the high infectivity.

“Importantly, the Omicron-L452R variant enhanced the ability of Omicron to infect lung tissues of humanized mice. By dramatically enhancing the anaerobic glycolysis of host cells, the Omicron-L452R variant obtains enough energy and nucleotide material to replicate in human cells. Taken together, the L452R mutation dramatically increases the risk of the Omicron variant. Our data explain why the Omicron variant has decreased fusogenicity and suggest that whether the L452R mutation is present in the Omicron variant should be closely monitored, and specific therapeutic antibodies and vaccines that target the L452R mutation should be developed,” the researchers wrote.