Neither double mutant, nor do we know what effect it has


Ignacio López-Goñi



The variant B.1.617 was first detected in India in October 2020, but the fact that it was described for the first time in that country does not mean that this is its origin. To date, it has already been detected in 21 countries. It is listed, for the moment, as a variant under investigation.

It has 13 mutations that result in amino acid changes. It has been described as a “double mutant”To refer to two specific mutations in protein S (E484Q and L452R), but it is a term that should be avoided because it has many more mutations.

Of all the mutations, those of concern are those found at positions 484, 452, and 681 of protein S. The first two are in the receptor-binding zone (RBD), while the third is located near the protein furin cleavage site. That is why it is believed that they could affect the interaction of the virus with the cell.

The E484Q mutation it involves a substitution of the glutamic amino acid -E- for glutamine -Q- at position 484. It is in the same position as the E484K mutation described in variants B.1.351 (“South African”) and P.1. (“Brazilian”) and others.

The L452R mutation it involves a substitution of the amino acid leucine -L- for arginine -R- at position 452. It is a mutation that is also present in the California variant B.1.429 / 427.

The P681R mutation involves the substitution of a proline -P- for an arginine -R- at position 681. In variant B.1.1.7 (“British”) there is also a mutation at that position, but in this case it is P681H.

These mutations in other variants have been experimentally related to an increase in the affinity of the virus protein for the human ACE2 receptor. This could facilitate entry into the cell and increase infectivity. It has also been suggested that, in some cases, antibodies in the plasma of convalescent patients had a lower neutralizing power against these variants, suggesting that these variants of the virus with these mutations could escape the antibodies of the immune system.

This, however, It does not mean that these variants will necessarily escape the control of vaccines. At this time we do not know. More evidence is needed to understand how this combination of mutations may affect the biology of the B.1.617 variant.

A variant with three lineages

The latest sequencing data show that there are actually three lineages of this variant, named B.1.617.1, B.1.617.2, and B.1.617.3, with small differences and different geographic distributions.

In March, the Indian Ministry of Health published a report stating that this variant B.1.617 was predominant in India, already present in 60% of isolates. At the same time we are seeing a dramatic increase in cases in that country. Is the new variant the cause of such an explosion of Covid-19 in India? At the moment we do not know.

We do not know how many isolates are being sequenced or if the rate of sequencing has increased. We cannot rule out that more cases are now being detected, simply because more is being sequenced. As the number of sequences available is still low in relation to the number of cases in India we must be very cautious. If we have for example 1,000 sequences of the Indian isolates in more than 4 million cases, what we are seeing is not representative.

We do not know if there are more cases because the variants are more infective or if more cases of this variant are detected because transmission has increased for other reasons. India has more than 1,400 million inhabitants: lots of people, close together and moving, best for aerosol transmission of a respiratory virus. It does not appear that strict measures of confinement, hygiene, social distancing and the use of masks have been implemented in India.

What’s more, India has only vaccinated 2% of its population. The safe health system that has major structural deficiencies. And, although the virus can infect anyone, the most disadvantaged sectors are always much more vulnerable.

However, due to the increase in the number of cases in India and that variant B.1.617 is the predominant, regardless of the fact that other more transmissible variants are circulating, we must be vigilant.

All this also shows that the problem of the pandemic is global and that what happens in a place as far away as India could affect us directly. Vaccines must go everywhere. And two more lessons: you have to sequence the largest number of isolates and you have to vaccinate in a hurry.

Ignacio López-Goñi. Professor of Microbiology, University of Navarra.

This article was originally published on The Conversation.

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