What is the 'D614G mutation' in COVID-19?

The SARS-CoV-2 virus that causes the COVID-19 pandemic proliferation throughout the world also accumulates mutations. As per a paper published in the journal mBIO, the D614G mutation has become the dominant variant in the COVID-19 pandemic.

A study which was conducted over 5,000 COVID-19 patients revealed that the mutation is an outcome of the neutral drift and the response generated by our immune system against the virus. Here, the neutral drift refers to the random genetic changes in the virus. These changes neither account for any special benefit to the virus nor do they harm it. 

During the initial wave of the pandemic, around 71% of the positive cases in Houston had this mutation and after the second wave, this particular variant rose up to a staggering 99%, outnumbering the other mutations. 

Ilya Finkelstein, Associate Professor of Molecular Biosciences at The University of Texas and co-author of the study stated, "The virus is mutating due to a combination of neutral drift -- which just means random genetic changes that don't help or hurt the virus -- and pressure from our immune systems."

In July, a study published in the journal Cell, analysed around 28,000 viral genome sequences from across the world discovered that the D614G mutation was dominating at a global scale. The study revealed that during the initial wave of the pandemic, the D614G strain was not the dominating strain, but slowly it picked up and began dominating all other strains.

What is COVID-19 D614G Strain and Where it is found?

What is D614G mutation?

The D614G mutation occurred in the spike protein of the virus-- protein which helps the virus to bind to the ACE2 receptor present in our cells. 

In D614G mutation, the infection supplanted the aspartic acid (D) in the 614th position of the amino acid with glycine (G) and hence, the change is known as D614G. This mutation was first identified in China and afterwards in Europe which later spread to nations like the U.S., Canada, and eventually in India.

Impact of  D614G mutation on human cells

As mentioned above, the D614G mutation occurred in the spike protein of the virus which helps it in attaching more efficiently with the ACE2 receptor in the human host, thereby making it more successful in entering a human body than others. 

Dr. Lipi Thukral, Senior Scientist at CSIR-Institute of Genomics and Integrative Biology (IGIB) in an email to The Hindu stated, '“You can think of the spike protein as a massive ‘trimer’ assembly with three protein chains. Each protein chain has two sub-units (S1 and S2). The sub-unit S1 is the one that attaches to the host cells — Human ACE2 receptor. The S2 sub-unit mediates the fusion of the viral and human membranes. The D614G mutation is present in the sub-unit S1 of the protein and is also close to the S2 sub-unit. Therefore, it has an impact on the human cell’s interactions with both S1 and S2.” 

A preprint posted in medRxiv (yet to be peer-reviewed) revealed that the D614G mutation showed increased infectivity and also displayed greater ability at attaching itself to the cell walls inside an individual’s nose and throat, increasing the viral load.

How prevalent is this mutation in India?

Dr. Anu Raghunathan, Senior Principal Scientist at CSIR-National Chemical Laboratory in an email to The Hindu stated, "The D614G mutation, which is the defining mutation for clade A2 of the virus, is indeed, quite prevalent in India."

A preprint study posted on bioRxiv revealed that the D614G was one of the most prevalent spike mutations during the initial phase of the pandemic in India. The D614G mutation has increased over time to 70% and above in most of the states except Delhi. 

Samples of the positive patients of COVID-19 for this study were collected from various states including Delhi, Tamil Nadu, Maharashtra and Uttar Pradesh. 

Will the D614G mutation impact the research on the vaccine?

A paper in the journal, Nature, conducted a study on Hamsters concluded that the D614G mutation may not reduce the ability of vaccines in clinical preliminaries to protect against COVID-19 and the therapeutic antibodies should be tested against the circulating variant of the virus before clinical development.  

The paper, however, fails to establish any link between the D614G mutation and the increase in the severity of COVID-19 or its impact on the mortality of the patients. The patients infected with this mutation show variable reactions depending on certain factors such as age, exposure to other diseases, genetic constitution and so on. 

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