DNA Explainer: Why Delta spreads so much faster than all other COVID-19 variants

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was the name given to the new virus on February 11, 2020, when last year the COVID-19 pandemic struck. This name was chosen because the virus is genetically related to the coronavirus responsible for the SARS outbreak of 2003.

Since the start of the pandemic, scientists have been developing a detailed understanding of how this SARS-CoV-2 infects cells. This will be helpful in preventing the spread of the virus and help in improved treatments and vaccines. Scientists are also trying to learn why the latest strains, such as the Delta variant, are more transmissible.

Understanding the virus

Many viruses have glycans covering their outer proteins, camouflaging them from the human immune system.

Rommie Amaro, a computational biophysical chemist at the University of California, San Diego did an experiment last year.

Amaro's laboratory group and collaborators created the most detailed visualisation yet of this coat, based on structural and genetic data and rendered atom-by-atom by a supercomputer.

On March 22, 2020, she posted the simulation on Twitter. A researcher questioned, what was the naked, uncoated loop sticking out of the top of the protein?

Though Amaro could not give a reply, structural biologist Jason McLellan at the University of Texas at Austin responded to the question. 

He said that the uncoated loop was a receptor-binding domain (RBD), one of three sections of the spike that bind to receptors on human cells.

In Amaro’s simulation, when the RBD lifted up above the glycan cloud, two glycans swooped in to lock it into place.

When Amaro mutated the glycans in the computer model, the RBD collapsed. McLellan's team built a way to try the same experiment in the lab.

By June 2020, the collaborators had reported that mutating the two glycans reduced the ability of the spike protein to bind to a human cell receptor1.

Full length SARS-CoV-2 spike protein with glycans running in MD shows vastly altered accessibility for small molecules and antibodies (aka #glycotime for the #COVID19 #demogorgon) @LCasalino88 (movie) @zied_gaieb @abbydommer @AmaroLab pic.twitter.com/uNtLvYDCRn

— Rommie Amaro (@RommieAmaro) March 22, 2020

Why does the virus spread so quickly?

Scientists have discovered key adaptations that help the virus to grab onto human cells with surprising strength and then hide once inside.

As it leaves cells, SARS-CoV-2 executes a crucial processing step to prepare its particles for infecting even more human cells.

These are some of the tools that have enabled the virus to spread so quickly and claim millions of lives.

Compared with SARS-CoV, SARS-CoV-2 binds to ACE2, an estimated 2 to 4 times more strongly, because several changes in the RBD stabilise its virus-binding hotspots.

Worrying variants of SARS-CoV-2 tend to have mutations in the S1 subunit of the spike protein, which hosts the RBDs and is responsible for binding to the ACE2 receptor.

How variants behave

The Alpha variant includes ten changes in the spike-protein sequence, which result in RBDs being more likely to stay in the 'up' position. 

The Delta, which is now fast spreading around the world and is a variant of concern, hosts multiple mutations in the S1 subunit.

This includes three in the receptor-binding domain (RBD) that seem to improve the RBD's ability to bind to ACE2 and evade the immune system.

Once the viral spikes bind to ACE2, other proteins on the host cell's surface initiate a process that leads to the merging of viral and cell membranes.

Why Delta variant spreads faster

The Delta variant, scientifically termed as B.1.617.2 of coronavirus, is a combination of two mutations that make it more transmissible and infectious than other variants.

The virus strain is known to spread faster than any other variant in the world and has become one of the most dominant strains in the United Kingdom.

At present more than 80% of new US COVID-19 cases are caused by the Delta variant, as per the Centre for Disease Control and Prevention (CDC).

The Delta variant carries the genetic code from two other mutations - E484Q and L452R, making it easier for it to break into the human immune system and invade the organs.

New variants tend to alter the structure of the spike protein and are more efficient in attaching themselves to the human host cells and multiply swiftly. This does more damage than the original strain.

Experts also believe that the B.1.617.2 lineage of coronavirus can dodge antibodies provided by vaccines as well as past COVID infections.

Delta variant has the ability to escape natural, as well as vaccine-induced immunity and that is a matter of grave concern.

According to a study by China's Guangdong Provincial Center of Disease Control and Prevention, people infected with the Delta variant had a high viral load. 

This is leading to the faster spread of the virus from one person to another and as a result, more serious symptoms and complications are seen.

The study indicates that the Delta variant replicates and multiplies at a faster rate than the original strain, making a person more prone to severe infection.