A single mutation at a critical site on the spike protein may have helped Delta variant spread like wild fire, found a team of researchers in the US, which included a researcher of Indian descent.
The findings published by researchers led by Pei-Yong Shi, a virologist at the University of Texas Medical Branch in Galveston in the US in a pre-print last week would probably explain why the hyper-infectious Delta variant replaced other circulating SARS-CoV2 strains in a short span of time.
Delta, first identified in India in October last year, has since then spread to 119 countries. In a span of three months, the prevalence of the Delta variant increased from 1.3 per cent to 94.4 per cent, displacing the previously predominant Alpha variant whose prevalence plummeted from 70 per cent to 2.4 per cent in the same period. In India too, most Covid-19 cases during the second wave were caused by the Delta mutant.
P681R in the spike protein
The study, to which Vineet D Menachery, a virologist of Indian descent, also contributed, identified that a single mutation called P681R in the spike protein – spike-shaped protein that helps the virus latch onto the human cells — is responsible for the enhanced transmissibility of the Delta strain. Studies have shown that Delta is nearly 40 per cent more infectious than the Alpha variant, hitherto considered to be the most highly transmissible mutant.
It is called P681R because of swapping of an amino acid called proline with another called arginine at position 681 on the spike protein. This change falls within an intensively studied region of the spike protein called the furin cleavage site. This single change mutation is capable of revving up Delta’s entry into the cells, the scientists showed through a series of experiments.
“Although key variants tend to have an eclectic combination of mutations, a single mutation in a key location can also make a big difference. We saw this with the ‘D614G’ mutation in mid-2020, although, as we predicted, it didn’t impact on vaccines,” said SS Vasan, Covid-19 project leader at Australia’s science agency CSIRO, who is unconnected with the current study.
“We have been following the P681R mutation with interest. Although it’s only a moderately conservative change of amino acid, it occurs at the right location known as the ‘furin cleavage site’, allowing the spike protein to be cut efficiently. Having said that, P681R is also present in other key variants such as Kappa, so it is premature to attribute Delta’s characteristics to just this single mutation even if it’s a critical one,” he added.