“FLip” mutations of SARS-COV-2 may be evading immunity and leading to surge in COVID cases, suggest researchers

The omicron subvariant JN.1. is likely to soon become the dominant lineage of the SARS-CoV-2 virus worldwide, according to researchers at the University of Tokyo. The subvariant has a mutation in its spike protein, L455S, also called a “FLip” mutation.

Experts told Down to Earth that a dominant strain need not necessarily indicate that it is more dangerous, as it is the nature of the virus to mutate.

On December 18, 2023, JN.1, was designated a separate variant of interest (VOI) after a rapid surge in recent weeks. JN.1 is a descendant of the BA.2.86 lineage, which first emerged in August 2023. 

BA.2.86 carries more than 30 mutations in the spike protein. It is distinct from the other omicron XBB lineages, such as EG.5.1 and HK.3 currently in circulation.

JN.1 (BA.2.86.1.1) evolved out of BA.2.86 in late 2023. Besides L455S in its spike protein, JN.1 is identical to BA.2.86. Similarly, the EG.5 sublineage variant HK.3 acquired the L455F mutation.

L455S and L455F are called “FLip” mutations because they switch the positions of amino acids F and L on the spike protein, increasing their transmissibility. Another example of the “FLip” mutation is F456L, which was found in several XBB descendant strains developed this year, such as XBB.1.5.10, FE.1, and FD.1.1.

Researchers at Peking University in Beijing ascertained in The Lancet Infectious Diseases, “With just one additional receptor binding domain mutation (L455S) compared to its predecessor BA.2.86, the JN.1 variant rapidly became predominant in France, surpassing both BA.2.86 and the so-called FLip (L455F+F456L) strains.”

Towards the end of November 2023, JN.1 surpassed HK.3 in France and Spain. 

A single F456L or L455F substitution dampens the receptor binding capacity of angiotensin-converting enzyme 2 (ACE2). 

ACE2 is a protein found in the epithelial cells in different parts of the body, such as the lungs, heart, and kidneys. SARS-CoV-2 virus binds to ACE2 as an entry point through the virus’ spike-like protein on its surface. 

When either XBB.1.5+F456L or BA.2.86 + S: L455S are added, there is a much stronger binding to ACE2 and less protection against natural antibodies.

These results explain the evolution of recombinant sub-lineages of omicron such as XBB and BA.1, according to the study supervised by Yunlong Richard Cao, an assistant professor at the Biomedical Pioneering Innovation Center (BIOPIC), at Peking University.

The effective reproductive number (Re) of the omicron subvariant JN.1 in France, the United Kingdom and Spain is higher than other new variants (BA.2.86.1 and HK.3) with a growth advantage. Researchers at the University of Tokyo used a Bayesian multinomial logistic model to study the virology of the subvariant virus.

The Re refers to the number of potential new infections that could spread through an infectious individual in a population. It is an estimate used to gauge the transmissibility of a virus in an epidemic. 

It appears that the virus could potentially evade vaccination. Another study by BIOPIC studied individuals recovering after XBB infections. One cohort had 27 participants who experienced post-vaccination XBB breakthrough infections and another had patients reinfected with XBB after BA.5 or BF.7 breakthrough infections. Compared to BA.2.86, JN.1 displayed a significantly enhanced ability to evade immunity.

Closer home, INSACOG chief NK Arora told news agency ANI that there is no need for additional doses of vaccine at present. Only those aged 60 years or older, those with comorbidities and those taking drugs to suppress immunity, like cancer patients, have to exercise precautions.

With over 850,000 new cases and over 3000 new deaths, an increase of 52 per cent and a decrease of 8 per cent, respectively, were observed between November 20, 2023 and December 17, 2023 globally, according to the World Health Organization (WHO) on December 22, 2023. 

In the same period, India recorded 3,241 new cases and 21 deaths, the WHO said. The Southeast Asia Region reported over 9,200 new cases, a 388 per cent increase.

However, reported cases do not accurately represent infection rates due to the reduction in testing and reporting. COVID-19-specific reporting has integrated into respiratory disease surveillance testing and reporting globally.

The Union health ministry data updated at 8 am on December 23, 2023 showed 752 new coronavirus infections. Four deaths were reported, two from Kerala and one each in Rajasthan and Karnataka. 

The Centers for Disease Control and Prevention (CDC) in the United States said that for the two weeks ending on December 23, 2023, JN.1 is expected to account for 39-50 per cent of all SARS-CoV-2 variants. “That’s an increase from the projected prevalence two weeks ago of 15-29 per cent. We’re also seeing an increasing share of infections caused by JN.1 in travelers, wastewater, and most regions around the globe.”

“JN.1’s continued growth suggests that the variant is either more transmissible or better at evading our immune systems than other circulating variants. It is too early to know whether or to what extent JN.1 will cause an increase in infections or hospitalisations,” the CDC said.

Despite the upsurge, globally, EG.5 remains the most reported VOI  but has shown declining trends over the past few weeks. 

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