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Explained: Understanding an abundant, highly transmissible coronavirus mutation

Written by Tabassum Barnagarwala
| Mumbai |

Updated: October 1, 2020 10:08:20 am

RNA viruses such as SARS-CoV-2 mutate slowly as they require a host (human cell) in order to replicate. (File Photo/Representational)The coronavirus SARS-CoV-2 is constantly mutating, but one mutation in particular has caught the eye of researchers for its abundance. Named D614G, this mutation has been found more transmissible than most others.
What is D614G mutation?
All viruses mutate to adapt to the barriers that humans put up. RNA viruses such as SARS-CoV-2 mutate slowly as they require a host (human cell) in order to replicate.
Until now, 12,000 mutations have been documented in over 3.2 crore cases globally. One mutation has been found the most widespread. It was first noticed in China and Germany, but gained attention when it cropped up in several cases across Europe, and eventually in the US, Canada, Australia and India. In this mutation, glycine (G) replaces aspartic acid (D) in the 614th position in the amino acid. Hence the mutation came to be referred as ‘D614G’.
IND614G,G (glycin) replaces D (aspartic acid) in 614th position. (Korberet al/Cell)What makes this mutation unlike others?
To understand this, we must understand how SARS-CoV-2 enters a human cell. The amino acids where mutation occurs are located in the spike protein of the virus. The spike proteins binds with the ACE2 receptor on the human cell and gains entry.
Dr Rajesh Pandey, scientist in CSIR-Institute of Genomics and Integrative Biology, explained, “It is the peptides in the spike protein that lock with the ACE2 receptor. In D614G mutation, two of the three peptides open up, making chances of entry into human cell higher. Imagine a hand with three fingers. If only one finger opens, it has limited access to pick up objects, but if two fingers open, they can pick up more objects. The two peptides increase chances of the virus entering a human cell.”
Because its nature allows a better chance of entering a host cell than other mutated strains, D614G has a higher rate of transmission. GISAID, a global virus database that has documented all circulating strains of SARS-CoV2, shows that the mutated strain gained prominence from March onwards in Europe.
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What are the implications of this?
A virus mutates every time it replicates in the human cell to adapt and survive. This mutation is helping the virus do exactly that. Until early March, this mutation was rare but gaining dominance in Europe, GISAID data shows.
A paper in Cell observed: “Prior to March 1, 2020, it (D614G) was found in 10% of 997 global sequences; between March 1 and March 31, 2020, it represented 67% of 14,951 sequences; and between April 1 and May 18, 2020 it represented 78% of 12,194 sequences.”
A pre-print paper in Medrxiv found patients infected with this mutation “had significantly higher virus load in the nasopharynx on initial diagnosis”. The study sequenced genomes of 5,085 SARS-CoV-2 strains in Houston.
The strain has grown, transmitted fast because of the ease with which it gains entry into the cell. “That is what gave it hype,” said microbiologist Dr Jayanthi Shastri, from Kasturba Laboratory, Mumbai. Shastri said initial studies showed D614G could lead to more transmission and severe symptoms. “Initially we did see severe infectivity, but as time went by it has been seen in our samples that infectivity cannot be directly linked with mutation, other co-morbid factors also play a role,” she said. So far, there aren’t enough longitudinal studies to draw a direct link between D614G and increased mortality. “For that we need to do genome sequencing for several severe patients to check if this mutation is present,” Shastri said.
Also in Explained | New research: Calcium-rich nasal salts shown to reduce exhaled aerosol
Is it prevalent in India?
The Lancet published a pre-print of Covid-19 reinfection in four health workers in Mumbai. The study by Kasturba Hospital, International Centre for Genetic Engineering and Biotechnology, and CSIR- Institute of Genomics and Integrative Biology found D614G mutation in three of them. “In one doctor who got reinfected the second time, D614G mutation was present. He developed severe symptoms and required plasma therapy. But we cannot be sure to directly link D614G with severity of infection,” Shastri said.
In another doctor, D614G was present in the first infection but it did not lead to severe symptoms.
Whether the mutation can cause death, or can be tackled by vaccines is not fully known. Some studies have indicated it does not lead to severe infection in the lungs.

Is it a vaccination target?
Its abundance offers researchers a chance to study and target its mechanism. Pfizer is working on a vaccine candidate in which antibodies will block the receptor-binding domain in the virus. The vaccine’s German trial has shown promising results against the D614G strain.
A pre-print paper in Biorxiv on September 2 was optimistic that the mutation may not reduce a vaccine’s effectiveness against it.
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