June 23, 2021

expert comment on the ‘Delta plus’ variant (B.1.617.2 with the addition of K417N mutation)

There have been several reports of a ‘Delta plus’ variant causing concern in India and detected in the UK.

Prof David Robertson, Head of Viral Genomics and Bioinformatics, MRC-University of Glasgow Centre for Virus Research (CVR), University of Glasgow, said:

“We don’t know yet if AY.1 has any extra advantage over Delta, but it would seem unlikely as the difference is only the mutation K417N.  This change slightly reduces binding affinity to ACE2.  We already know Delta itself (the virus that is now dominant in the UK) seems to be definitely more transmissible and that would appear to be a big part of its fast spread.”

Prof Ravi Gupta, Professor of Clinical Microbiology, University of Cambridge, said:

“As yet there is no clear evidence that the AY.1 is more transmissible or immune evasive than the Delta Variant.  The K417N mutation has previously occurred on a background of Alpha variant, without significant increased expansion in cases, and now Delta; it likely has little effect on infectiousness of the virus and could have a small effect on antibody binding responses post vaccination.”

Prof Francois Balloux, Professor of Computational Systems Biology and Director, UCL Genetics Institute, UCL, said:

How worried should we be about this variant?

“At this stage there is no particular cause for concern. The delta+ variant, also referred to as AY.1 is the delta (B.1.617.2) strain carrying the K417N mutation in the spike protein. There have been ~160 strains sequenced to date globally. The first was observed on April 5th 2021 in India. It has been found in several countries but has remained at extremely low frequency, with the exception of Nepal where it has been estimated at ~4% (but based on a tiny sample size 3/70). Delta+ represents 0.00002% of all delta variants sequenced to date. There is no evidence the strain is currently expanding in any country.

How worried should we be about the number of cases in the UK?

“Cases of delta+ in the UK remain at a very low level. The first case was observed on April 28^th 2021. The lineage has remained at very low frequency since with no sign of expansion.

What do we know about this variant and it’s transmissibility/ vaccine evasion/ lethality?

“Given the tiny number of strains reported, nothing is known about the transmissibility, immune evasion or lethality of the delta+ strain. Though, given that it has remained at very low frequency everywhere where it has been identified strongly suggest it is not more transmissible than its delta progenitor.

The K417N mutation

“The K417N mutation has arisen independently in several viral lineages (at least twice in delta). It was observed on the 27 March 2020 in a strain found in Qatar. K417N is generally present in the beta variant (1.351). The mutation may contribute to immune escape, though its impact on transmissibility is not clear-cut. None of the lineages carrying it (with the exception of beta) have been particularly successful so far.

Parallel with alpha

“There were earlier similar concerns when the alpha variant (B.1.1.7) acquired the E484K immune escape mutation. This happened several times independently but none of those alpha lineages carrying E484K were particularly successful in the end.”

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/covid-19

Declared interests

None received.