SARS-CoV-2 | Strains, Variants, Mutants and Recombination

The genome of SARS-CoV-2 consists of an mRNA single strand, packed at the heart of the virus, is the primary construct for its replication. The sequence contains information necessary for constructing the viral machinery proteins by the process known as translation. Below is an image showing the several viral proteins coded by the genetic material that is present in the virus [ref].

 

The physical structure of the virus that is made by several proteins is shown in the image [ref]. These proteins make up the structural machinery of the protein. The remaining viral machinery are called non-structural proteins (NSP) that are necessary for functions such as polymerization, inhibition, proof reading and many other that allow the virus to infect and replicate in host organisms.

The use of the terms mutants, variants and strains have become quite frequent in the news that we hear today. These phenomenon occur due to the process called recombination. Simply put, recombination is the combination of different genetic material during the process of its replication. A mutation is any kind of change in the genetic material that arise due to a mistake during replication or environmental factors. These can occur at specific positions on the coding sequence or can alter significant regions of a sequence. When many mutations are brought together within a single region such as the sequence coding for a given protein, a new variant emerges. When a gene variant expresses a distinct change in its properties, the new variant is termed as a new strain.

A virus such as the SARS-CoV-2 is quite prone to mutations due to recombination that may occur naturally. However these genetic changes may not be in that portion of the sequence that is coding for essential proteins such as their viral machinery. For example, The spike protein binds to the ACE2 receptor in host organisms leading to host entry. The region where the spike protein binds to the host receptor is termed as the receptor binding domain (RBD). A mutation in this region of the protein sequence can alter the affinity or binding of the virus to a host cell which makes a new strain. Taking the gene of the virus that originated from Wuhan, China as a template/parent variant, the first interesting mutation was the D614G (The Aspartic acid (D) residue at position 614 in the protein sequence is mutated to a Glycine(G) residue) that was found to correspond to the spike protein region of the protein sequence [ref]. This variant was prevalent all over the world for a long duration of the year 2020.

The mutations in the virus are constantly being tracked by researchers across the globe. A current scenario of all the different mutation observed are represented in the following image [ref].

Track based on Mutants: Mutations that generally occur in the spike protein are very interesting since they play a vital role in the viral activity. However, the number of mutations are so vast that very few of them are interesting variants. Few of these variants make new strains that have altered properties.  

• D614G is the most common variant that has been found to be prevalent all across the globe. Most of the new vaccines that target the spike protein have been found to be effective against this mutant. 
• V483A and G476S are primarily observed in samples from the United States.  
• V367F is found in samples from Hong Kong, France and the Netherlands. The V367F and D364Y variants have been reported to enhance the structural stability of the spike protein facilitating more efficient binding to the ACE2 receptor.
  

Track based on geography: The term lineage is given to  any genetic information that is uni-parent-ally transmitted without recombination thereby exclusively generated due to mutation. Hence using a lineage it is more simple to track mutations in the virus. Several mutations can exist within the same lineage.  For example, the D614G mutant is commonly found in the B.1 lineage.

• In the United Kingdom (UK), a new variant of SARS-CoV-2 (known as 20I/501Y.V1, or B.1.1.7) emerged with a large number of mutations. This variant was reported in the US at the end of December 2020.
• In South Africa, another variant of SARS-CoV-2 (known as 20H/501Y.V2 or B.1.351) emerged. This variant was reported in the US at the end of January 2021. 
• In Brazil, a variant of SARS-CoV-2 (known as P.1) emerged. This variant has 17 unique mutations, including three in the receptor binding domain of the spike protein. This variant was detected in the US at the end of January 2021.
• In India, a "double variant" (known as B.1.617) is found to be common. 
• The B.1.526 variant is found in New York City.

Studying these variants and strains are important. They tell us a lot about the virus and its virulence. New strains can be identified due to alteration of several factors such as the variation in:

• transmission,
• susceptibility,
  
• mechanism of entry,
• severity of infection,
  
• primary/secondary symptoms.

These factors are also important in the study of effectiveness of medication and vaccines. For a graphical compilation of most of the variants and lineages browse this NYT post.