‘Double mutant, triple mutant, Bengal lineage’ — Covid variants driving India surge decoded

India has seen emergence of at least two unique mutations of SARS-CoV-2, but there are other infectious variants around the world that could be a factor too.

Representational Image | The novel coronavirus | Pixabay file photo

Bengaluru: As India reels under a surge of new Covid-19 cases and deaths, experts have theorised that the new wave of infections is driven by the ‘double mutant’ variant discovered in the country, the B.1.617.

While the evidence is still inconclusive owing to lack of sequencing infrastructure and power, the experts say the ‘double mutant’ is likely to become the dominant form of the SARS-CoV-2 virus in India and some countries abroad.

But the B.1.617 is not the only mutation driving the current surge; so far, over 7,000 individual mutations of the SARS-CoV-2 virus have been documented in India.

ThePrint takes a look at the ‘double mutant’, which some reports are incorrectly identifying as a ‘triple mutant’, and other key forms of the virus responsible for the second wave of Covid infections globally.

What are ‘variants’, ‘mutations’ and ‘lineages’?

All viruses mutate as they replicate, as a part of natural processes — a mutation occurs when there is an ‘error’ or change in the RNA sequence of the virus as it replicates. Some viruses mutate faster than others, such as the influenza virus.

Mutations are written down in the form of which nucleotide or amino acid is changing, and at what position in the sequence. For example, the E484Q mutation affects the spike protein of the SARS-CoV-2 virus in a way where the amino acid ‘E’ (glutamic acid) is replaced by the ‘Q’ (glutamine) at the 484th position.

As a virus mutates, it can sometimes retain some mutations while also giving rise to more along the way and retaining those. Multiple mutations that spread persistently give rise to a new ‘variant’ of the virus, such as the India variant or the UK variant, also called ‘lineages’.

Some of these variants carry mutations that can escape detection by the immune system and neutralising antibodies, or spread faster, or infect more, causing severe disease, or a combination of these three behaviours. When variants ‘under investigation or interest’ acquire mutations that demonstrate any of these behaviours, they are designated as ‘variants of concern’.

If a variant displays major consequences, such as completely escaping the effects of a vaccine or driving extremely high mortality, it can become designated as a ‘variant of high consequence’. So far, there aren’t any in this category.

Variants of concern

‘Double mutant’ B.1.617

The Indian ‘double mutant’ variant carries two important mutations: L452R and E484Q. Both these mutations have been associated with evading the immune system, while the L452R mutation has been associated with a rapid spread of cases. The variant is most likely to be the leading cause behind the sudden and staggering growth in numbers being witnessed in India.

The B.1.617 variant also carries another notable mutation, P681R, misidentified in some reports as P614R. However, the mutation is not new and has been a part of the variant for a while.
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The ‘triple mutant’ descriptor came along because of a mutation of interest, V383L, that is now present on the spike protein. It is found primarily in samples sequenced from Maharashtra. ​With available data from other countries where it has been detected before, it doesn’t seem to warrant much concern at the moment.
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​​​”There is no scientific term such as “double” or “triple” mutation of virus,” clarified a spokesperson for the science ministry on Friday. “The terms double or triple mutants are colloquial and these are used to emphasize features of a variant. Double or triple mutations as used recently in various media reports, were to signify the number of mutations which escape immunity (immune escape mutant). These variants otherwise harbour 15 lineage defining mutations.”

Additionally, all variants around the world carry multiple mutations — many more than three.

​B.1.617 was originally discovered in October, and has since been detected in multiple countries, including the UK, USA, Germany, Australia, New Zealand, South Korea, Turkey and Nigeria.

The other ‘Indian variant’ B.1.618

India is also seeing a new ‘variant of interest’, called the B.1.618, which is currently said to be spreading rapidly in West Bengal.

It carries a different set of mutations to the ‘double mutant’.

The B.1.618 is characterised by E484K (which virologists informally call ‘Eek’), a major immune-escape mutation. It also carries two ‘deletions’ in its spike protein, called H146del and Y145del. Both these have been associated with immune escape as well. The variant carries other modifications not associated with the spike protein too.

This lineage is characterized by a 6 nt deletion (H146del &Y145del) , apart from E484K and D614G in spike protein
Other variants are in the ORF1ab, ORF3a, ORF7a, ORF7b and N genes pic.twitter.com/fuY6lefta8

— Vinod Scaria (@vinodscaria) April 20, 2021

This variant has also been found in other countries like the USA, Switzerland, Singapore, and Finland, but not with the full suite of mutations found in India.

There is currently not enough evidence to indicate that the variant is driving the spread in West Bengal, and experts have clarified that investigation is needed into it to understand its behaviour.

‘UK variant’ B.1.1.7

This variant first emerged in the UK and has been associated with a 30-50 per cent increase in transmission. It also likely has an increased disease severity and higher viral load upon infection.

The variant does not demonstrate immune escape properties, and multiple vaccine manufacturers have assured the public that their products are effective against it. It now comprises over 95 per cent of all infections in the UK, and has been identified in at least 114 countries.

The most notable mutation the B.1.1.7 carries is the N501Y, which has been determined to enhance affinity to the ACE2 receptors in humans that the virus uses to latch on. Additionally, the P681H mutation could potentially affect cell infectivity and replication of the virus.

A sub-variant, nicknamed the Bristol variant, also seems to have evolved the E484K mutation, which has been shown to be immune-evasive.

‘South Africa variant’ B.1.351 (501.V2)

This variant emerged in South Africa and has been associated with both increased infectivity as well as immune escape.

It carries three notable mutations — E484K, N501Y, and K417N — and five others on the spike protein. It also carries multiple mutations in other regions. The variant has been most concerning on the vaccine front, with multiple trials reporting lower efficacy in neutralising this variant.

The B.1.351 has also been detected in other countries such as USA, Singapore, China, and in multiple African and European Union countries.

Brazilian variant P.1

This variant emerged in Manaus, Brazil, and drove the second wave of infections in the state of Amazonas. It is associated with immune escape and increased infectivity.

There are ten key mutations in the spike protein that make up this variant, including N501Y, E484K, and K417T, the last of which increases the virus’s ability to bind to human cells. It also has ‘insertion’ mutations away from the spike protein.

It is as yet unclear how effective vaccines are against this variant, but some have demonstrated neutralising ability while some have shown reduced efficacy.

The P.1 variant has also been detected in other countries in the EU and South America, as well as Japan, Turkey, UK, and India.

There is also a P.2 variant in Brazil, which carries only the immune escape E484K mutation but not the other two.

Other variants of interest or concern in more localised areas around the globe include B.1.429 and B.1.427 in the US, P.3 in Philippines, and B.1.525 in the UK and Nigeria that are currently under investigation.

(Edited by Shreyas Sharma)