- Structure of SARS-CoV-2
- Spike protein
- SARS-CoV-2 variants
- What Changes in Variants
- Research and countermeasures
The sources consulted for preparing this editorial content are the official sites of the WHO and the CDC and scientific articles published on private websites dedicated to scientific research, such as Nature.com and the National Center for Biotechnology Information (NCBI).
In the context of the current COVID-19 pandemic, the emergence and spread of the New SARS-CoV-2 Coronavirus variants have raised further concerns among people worldwide.
All viruses, especially RNA viruses like SARS-CoV-2, tend to continuously mutate their genetic material to form new variants. This behavior is justified because varying them could give them characteristics. That improve their survival, pathogenicity, transmissibility, or ability to circumvent the acquired immunity. Obtained from a previous infection or a vaccine.
Clearly, variants resulting from the tendency to change are not always functional; very often, the product of mutation does not bring any particular benefits.
This article seeks, in essence, to analyze the mutations that characterize the current variants of SARS-CoV-2. For a better understanding of the content, of course, it also includes a brief review of the New Coronavirus reference structure.
Did you know that…
The more a virus continues to circulate, the more likely it is to mutate.
To explore:
Coronavirus 2019-nCoV: How to Recognize First Symptoms And What To Do
Structure of SARS-CoV-2
As is done by SARS-CoV-2: Structure, Genome and Protein
SARS-CoV-2 is a positive single-filament RNA virus with pericapside (or envelope).
The pericapside is a kind of wrapping around the head of some viruses. it consists of phospholipids and glycoproteins.
SARS-CoV-2 has a genome of 29,881 nitrogen bases, which encodes for 9,860 amino acids.
This genome is divided into genes for structural proteins and genes for non-structural proteins.
The genes for structural proteins encode for spike protein (abbreviated in S), pericapside protein (abbreviated in E, enveloped), membrane protein (abbreviated in M), and nucleocapsid protein (abbreviated in N).
As the name suggests, structural proteins contribute to forming the structure of SARS-CoV-2.
Genes for non-structural proteins, on the other hand, encode for proteins, such as protease similar to 3-chymotrypsin, para pin-like protease, or RNA polymerase RNA-addict. Whose functions are regular and direct the process of replicating and assembling the virus.
Although all the elements listed above are important, this article merely reviews the characteristics and functioning of the spike protein, as it is the true protagonist of this theme, namely the SARS-CoV-2 variants.
Did you know that…
SARS-CoV-2 shares approximately 82% of its genome with the SARS-CoV coronaviruses (responsible for SARS) and MERS-CoV (responsible for Middle Eastern Respiratory Syndrome).
To explore:
SARS-CoV-2: Structure, Proteins and Pathogenesis of the New Coronavirus
Spike protein
Structure of SARS-CoV-2 Spike Protein
The spike protein (or S protein) of SARS-CoV-2 (and all known Coronaviruses) rugs the outer surface of the virus, forming those protuberances that give the New Coronavirus the appearance of a crown (the term “Coronavirus”).
The spike protein weighs 180-200 kDa (read kiloDalton) and comprises 1,273 amino acids.
Spike consists of two major amino acid components, called subunits S1 (14-685) and subunits S2 (686-1.273):
The subunit S1 hosts a sequence of amino acids known as RBD (the English acronym for “Receptor Binding Domain”, which binds to the receptor). Which is essential to bind the virus to the host cells (the human being).
The subunit S2, on the other hand, is the site of amino acid sequences (fusion peptides, HR1, HR2, a transmembrane domain, and cytoplasmic domain). The ultimate function is to facilitate the fusion and entry of the virus into the host cells.
In its native state (i.e., when the virus is not infecting anyone), the spike protein is in the form of an inactive precursor. But as the virus encounters a potential organism to infect, it immediately passes to an active state. The activation process is triggered by the protease of the target cells (so it is the host itself that activates it!), which “break” the spike and form subunits S1 and S2.
How SARS-CoV-2 Spike Protein Works
The SARS-CoV-2 spike protein is complex to operate; the article in question aims to simplify it as much as possible so that readers can understand it.
The spike protein is essential to initiate the host infection process; In other words, it’s the weapon the New Coronavirus uses to cause the infection known as COVID-19.
Spike’s infection process can break down into two moments:
- The link to the host cell. It’s the stage where the virus attacks and binds to the organism’s cells that will then infect.
- The fusion of the viral membrane (in essence the virus) with the host cell membrane. It’s the phase that allows the virus to penetrate the cells of the infected organism and spread its genome to it.
Link to host cells
The spike protein connects to the host cells through the RBD sequence of subunit S1.
Scientific studies have shown that the RBD sequence is linked to the host cells by interaction with the ACE2 receptor on the surface of the plasma membrane of the cells themselves.
ACE2 is an enzyme and is the equivalent of ACE, the protein used to convert angiotensin 1-9.
In human beings, ACE2 is found primarily on the surface of the plasma membrane of the cells of organs such as the lungs, intestines, hearts, and kidneys.
Once the subunit S1 is bound to ACE2, the protein S begins to change conformation; this event is intended to facilitate the fusion phase and introduce the virus into the host cell.
The link to ACE2 and the resulting conformational change are two key aspects for developing the SARS-CoV-2 vaccine and understanding the host’s antigenicity and immune response mechanisms.
However, one problem needs to be considered: changes to the S1 subunit and, in particular to the RBD sequence, could change the way the conformational change develops; as a result, this could affect the antigen characteristics and effectiveness of vaccines.
Merging of the Host Cells
The spike protein fuses the virus to the host cell through the amino acid sequences of subunit S2.
The virus melting process shall take place on the wave of the conformational change of the S-protein induced by the link between the RBD and the host ACE2 receptor: spike’s conformation changes, in fact, bring the viral membrane closer to the plasmatic membrane of the host cell, all the way through the interaction, the membrane fusion, and finally, the swallowing of the infected virus.
Once the viral genome is inside the host cell, the virus begins replication. The infection process can be considered complete.
SARS-CoV-2 variants
What are the SARS-CoV-2 Variants?
There are three variants of SARS-CoV-2 that are of most significant concern: the English variant, the Brazilian variant, and the South African variant.
Between January and February 2021, Italy (and other European countries) reported cases of each of the above variants.
To explore:
SARS-CoV-2 Coronavirus Variant: What Are They And What Do We Know?
SARS-CoV-2 English Variant
In mid-December 2020, the United Kingdom authorities reported to the WHO (World Health Organization) the isolation of a variant of SARS-Co-V-2. It was the one that now has the name of the English variant (SARS-CoV-2) but is known among experts as the abbreviations: B.1.1.7, VOC 202012/01 and 20I/501.V1.
According to early evidence, the English variant SARS-CoV-2 would show greater transmissibility (faster and more efficient transmission). But would not cause a more severe infection and would have no impact on the vaccine’s effectiveness (i.e., the vaccines available today would protect against this variant).
A very recent survey (February 2021), however, could contradict the above: It seems that B.1.1.7 has changed again.
In conclusion, it should be noted that some studies of the English variant have shown evidence to support its increased pathogenicity. In this respect, however, experts agree that further investigation is needed.
To explore:
English Variant SARS-CoV-2: why are you worried?
Brazilian Variant SARS-CoV-2
The Brazilian variant of SARS-CoV-2 is also known as P.1 or 20J/501Y.V3.
His first award dates back to December 2020, after routine checks carried out in Japan at Haneda airport in Tokyo on four travelers from Brazil (hence the term “Brazilian variant”).
The news of his discovery was given by the Japanese National Institute for INFECTIOUS Diseases (NIID).
Studies so far suggest that the Brazilian variant has greater transmissibility. Also, it appears that it also has a different antigen profile, which is causing great concern: This means that the antibodies produced from pre-P.1 infection or those generated after the currently available COVID-19 anti-vaccination vaccinations cannot recognize and neutralize the Brazilian variant.
Recent epidemiological research has shown that in a region in Brazil where a high percentage of people had already contracted SARS-CoV-2 in the months before December 2020. There has been a rather unusual increase in the number of cases towards the end of 2020.
This event had led experts to suspect that the Brazilian variant could re-infect individuals who had fallen ill with COVID-19 before P.1 appeared.
South African variant of SARS-CoV-2
The South African variant of SARS-CoV-2 is also known as B.1.351 or 20H/501Y.V2.
Its first identification dates from the beginning of October 2020 in South Africa (hence the name ‘South African variant’) in Nelson Mandela Bay. However, the WHO report is dated shortly after: December 2020.
Meanwhile, other countries in Africa and the world have said they have isolated similar variants of SARS-CoV-2.
Preliminary studies appear to indicate that the South African variant has a higher viral charge and greater transmissibility. It also appears to hurt the vaccine’s effectiveness: one of the mutations that characterize it would allow it to circumvent the antibody defenses generated by the vaccine (or following an earlier infection).
The data collected so far are insufficient to establish whether the South African variant causes more serious disease.
What Changes in Variants
What are the Mutations of the New Coronavirus Variants?
All three of the most feared variants of SARS-CoV-2 currently in circulation are mainly characterized by spike protein mutations; here’s the previous review of this important viral protein.
By mutation of a protein, it can be understood as:
- The replacement of one or more amino acids.
- The deletion of one or more amino acids.
- The addition of one or more amino acids.
More precisely, the mutations concern the subunit S1, where RBD also resides, which is the portion of amino acids fundamental to the virus’s link to the host cells.
Within the spike protein, subunit S1 ranges from amino acid 14 to amino acid 685; RBD, which is included in this sequence, occupies the amino acid section 319-541.
For the central dogma of biology, the alterations in the amino acid sequence of a protein depend on mutations of the genetic material (whether DNA or RNA).
Mutations of the SARS-CoV-2 English Variant
Initially, the English variant SARS-CoV-2 had two mutations: position 501 and the other in position 681, and one in positions 69 and 70.
Then, in February 2021, some surveys found that some strains of the same variant have acquired a further mutation in position 484.
Here are the details of these changes:
In position 501, within the RBD sequence, thyroxine replaced an as particulate acid.
This mutational event is reported by the acronym N501Y, where N is the abbreviation for particulate acid and Y for thyroxin. In contrast, 501 says the position of the mutation within the SARS-CoV-2 genome.
The deletion of amino acids 69 and 70 (before the start of the RBD sequence) is often observed in the coronavirus spike protein.
It provides variability in the conformational exchange process that follows the link between the RBD and the host’s cellular receptor.
In position 681, after the RBD sequence (but still within subunit S1), a histidine replaced a proline.
This mutational event is described by the acronym P681H, where P is the abbreviation proline and H of histidine, and 681 indicates the mutation within the viral genome.
Position 681 is extremely variable in all Coronaviruses.
In position 484, in full RBD sequence, a lysine replaced a glutamic acid.
This mutation is referred to more briefly as E484K, where E is the abbreviation for glutamic acid and K for lysine. At the same time, 484 indicates the position of the mutation within the viral genome.
To understand…
In abbreviations describing the mutation of amino acid, the letter preceding the number indicates the original amino acid (the one replaced), the number indicates the position of the mutation, and the letter following the number points to the new amino acid.
Mutations of the Brazilian Variant of SARS-CoV-2
The Brazilian variant of SARS-CoV-2 has three mutations, all in the RBD sequence:
- In position 417, where a thyroxine replaced a lysine (K417T);
- In position 484, where a lysine replaced a glutamic acid (E484K);
- In position 501, where thyroxine has replaced a particulate acid (N501Y).
Mutation of the South African SARS-CoV-2 Variant
The South African variant of SARS-CoV-2 also has three mutations within the RBD sequence:
- In position 417, whereas particulate acid replaced a lysine (K417T);
- In position 484, where a lysine replaced a glutamic acid (E484K);
- In position 501, where thyroxine has replaced an as particulate acid (N501Y).
Spike E484K mutation: effects
According to early evidence, mutation of spike protein in position 484, by switching from glutamic acid to lysine, would interfere with the ability of antibodies produced following a vaccine (or previous infection) to recognize and neutralize the variant virus.
Simplifying, it appears that the mutation in question affects the effects of the currently available COVID-19 vaccines and is responsible for reinfection (the duration of immunization against COVID-19 infection is not yet known at this time).
It is no coincidence that experts define the E484K mutation as an “escape mutation”, meaning that it allows SARS-CoV-2 to elude the immune system and infect the host, even if vaccinated or already infected by an earlier version of the virus.
Research and countermeasures
SARS-CoV-2 variants: The objectives of Scientific Research
Currently, in collaboration with the WHO, national research groups are studying the different variants of SARS-CoV-2 in order to better understand:
- transmissibility;
- The potential for reinfection;
- Effects on vaccination;
- The severity of the disease caused;
- The effectiveness of diagnostic tests.
Also in cooperation with the WHO, the various national authorities are trying to understand the circulation of the different SARS-CoV-2 variants and their evolution.
SARS-CoV-2 variants: What countermeasures are being taken?
Countermeasures to prevent and spread the different variants of SARS-CoV-2 are the same as those adopted for the previous version of the virus, namely:
- Social distance;
- Hygiene of hands;
- Use of the mask;
- Good ventilation of enclosed areas;
- Avoid assemblies.