Mutation under lens
A variant of a Sars-Cov-2 typically has multiple changes in its genome – or mutations – which change how the virus can behave. The B.1.617 lineage is split into three -- B.1.617.1, B.1.617.2 and B.1.617.3 -- that largely have the same set of mutations, except for some small variations.
Among these, two are common: L452R and P681R (these letters mean the amino acid at site 452 changed from leucine to arginine and at site 681 from proline to arginine). Except for B.1.617.2, the other two variants also have the E484Q mutation.
“...Mutations in these variants may result in increased ACE2 binding and rate of S1-S2 cleavage resulting in better transmissibility, and possibly capacity to escape binding and neutralization by some monoclonal antibodies. In a preliminary study on hamsters, infection with B.1.617.1 resulted in increased body weight loss, higher viral load in lungs and pronounced lung lesions as compared to B.1 variants (D614G),” WHO said.
Several studies released by scientists in recent days have shown that some of B.1.617 family of the virus are more transmissible, lead to more severe disease, and be somewhat resistant to some lab-grown antibodies, but it isn’t clear yet if they can make vaccines or immunity from a past infection redundant to any significant degree.
In one of the studies, published late on Sunday, on Biorxiv, the researchers zeroed in on the P681R, which has also been seen in the variant first spotted in UK. “We find that P681R is associated with enhanced capacity to induce cell-cell fusion and syncitia formation, and that P681R alone confers this ability on the B.1.617.1 spike with RBD mutations L452R and E484Q ,” said the team of researchers led by scientists from Cambridge.
Syncitia is a phenomenon where multiple cells fuse to create what are known as giant cells. The scientists explained that the P681R mutation occurs at a location of the virus that takes the shape of a spike to first latch onto human cells, before it splits – or cleaves – in order to enter the cell. This site is known as the polybasic cleavage site (PCBS). “Virus infectivity and fusogenicity mediated by the PBCS is a key determinant of pathogenicity and transmissibility and there are indications that giant cells/syncitia formation are associated with fatal disease,” the authors said.
Among the assessments they carried out was the case analysis of 33 staff members of a Delhi health facility who were infected by the coronavirus after having been vaccinated, most of whom had contracted the new variant, although none developed severe symptoms.
“The loss of neutralisation of B.1.617 (by vaccinated serum) has likely contributed to an epidemic wave in India where background infection to the Wuhan-1 D614G in 2020 was between 20-50%,” said the authors in the study, which is yet to be peer reviewed.
“What we found was a reduction in the ability of the antibodies to neutralise this variant, but they weren’t ineffective. There are infections reported in vaccinated individuals but all vaccines protect against severe disease,” said Dr Anurag Agarwal, one of the authors of the paper and director of Institute of Genomics and Integrative Biology. “Breakthroughs are being seen with both (all) vaccines though. Not rare anymore, clearly. In vast majority, but not all, disease is mild,” he added.