Since its discovery, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has undergone multiple changes, resulting in various virus variants. The Delta version is the most recent and well-known of them. In comparison to previous SARS-CoV-2 variants, it is more contagious and infectious. As a result, the World Health Organization (WHO) and the US Centers for Disease Control and Prevention have identified the Delta variant as one of the variants of concern (US-CDC).
To combat the pandemic, vaccines against coronavirus disease 2019 (COVID-19) began to be administered worldwide in January 2021.
The vaccine is currently available in four forms: complete SARS-CoV-2 virus, adenovirus, mRNA, and subunit recombinant protein. Except for the SARS-CoV-2 viral vaccine, the majority of these vaccines are based on the Spike (S) protein found on the viral envelope. The S protein has 16 subdomains, the most important of which is the receptor-binding domain (RBD), which interacts with the host’s angiotensin-converting enzyme 2 (ACE2).
Separate neutralizing antibodies (Abs) were also created to treat COVID-19 patients in addition to vaccinations. All four vaccinations have different modes of action. Nonetheless, they all produce neutralizing Abs that protect a person from SARS-CoV-2 infection and prevent the virus from spreading.
The sites of mutation in the RBD of the Delta variation, as well as other variants of worry and variants of alert and interest, were examined in a recent review report published in Immune Network. This would help to locate the essential mutation sites in the variants and study the pandemic’s current predicament.
SARS-CoV-2 Alpha variant
SARS-Alpha CoV-2’s form was first reported in the United Kingdom (UK). This variation was discovered to be 50 percent more infectious, hospitalized, and deadly than the original strain. The S gene in the alpha form has 13 mutations, three of which are in the RBD (E484K, S494P, and N501Y), and the rest are in the functionally uncharacterized domain.
SARS-CoV-2 Beta variant
South Africa was the first to report the Beta variant. The S gene was discovered to have 10 mutations. Five of these mutations were found in the N-terminal domain (NTD) of S (L241del, L242del, and A243del) and the RBD (E484K, K417N, and N501Y). The Beta variant’s nine mutations are all found in the spike protein’s S1 region and C-terminal S2.
SARS-CoV-2 Gamma variant
Brazil and Japan were the first countries to report the Gamma variety. The S gene contains a total of 11 mutations. Except for T1027I, which is in the S2 region, the majority of the mutations are found in the S1 region. Except for K417, where T is replaced by N, three mutations in RBD, K417T, E484K, and N501Y, are nearly identical to the Beta variant. Because it lacks any deletions in the NTD domain, the Gamma variation differs from the Alpha and Beta variants.
SARS-CoV-2 Delta variant
The SARS-CoV-2 Delta type was originally discovered in India, and it quickly became the most common in European countries. During the same time period, two more variants, Kappa and B.1.617.3, were reported in India and are the closest variants to Delta.
The Delta variant shares three mutation sites with the Kappa and B.1.617.3 variants: L452R, D614G, and P681R. The D614G mutation, on the other hand, has been found in all four variants of worry, as well as all six variants of curiosity and alarm.
When compared to the Alpha model, the P681 is replaced with H instead of R in the Delta variant. The L452R mutation was also discovered in SARS-CoV-2 and variants from the United States. E156del, R158G, and T478K were three mutation sites that were unique to Delta.
SARS-CoV-2 variants of interest and alert
Six SARS-CoV-2 variants of interest and alert, as well as four concert variants, have been described. ,,,,, and B.1.617.3 were the variants in question. Only four mutation sites have been reported in SARS-CoV-2 and, which is the smallest number of mutations documented in any of the variants. The E484K and D614G mutation sites are also present in the variation. The D614G mutation can be found in all of the variants, while the E484K mutation can be found in eight of them.
The UK and Nigerian SARS-CoV-2 (B.1.525) variation has eight mutation sites, three of which are in the NTD of the S1 region: H69del, V70del, and Y144del. E484K and D614G are two common mutation sites, and A67V, Q677H, and F888L are three distinct mutation sites. There are 14 mutation sites in the New York (B.1.526) variation. This variant had mixed mutations in nine mutation sites that are shared by numerous variants, whereas five mutation sites, L5F, D253G, S477N, T859N, and Q957R, were found to be unique.
The Delta version is quite similar to the SARS-CoV-2 (B.1.617.1) and B.1.617.3 variants. T19R, G142D, L452R, D614G, and P681R are five mutation sites shared by these three variants. The D950N mutation is seen in both Delta and B.1.617.3, while the Q1071H mutation is specific to the variation. The mutant site E484Q of and B.1.617. Three variants are also found in the other variants, but with the letter K instead of the letter Q.
SARS-CoV-2 variations’ susceptibility to monoclonal antibody treatment
The FDA has issued an Emergency Use Authorization (EUA) for the use of unapproved monoclonal Abs against SARS-CoV-2 in an emergency situation. For the therapy of COVID-19, three monoclonal Abs are currently available: bamlanivimab plus etesevimab, sotrovimab, and casirivimab plus imdevimab.
The Alpha and Beta variants of SARS-CoV-2 were used to test the efficacy of the initial vaccine and the treatment with neutralizing Ab. Although there is some escape of these variants, the vaccination was proven to have protective benefits with adenovirus vector and mRNA vaccines. The Alpha version, on the other hand, demonstrated little or no resistance to monoclonal Abs. When bamlanivimab and etesevimab were used together, however, the Beta, Gamma, and variants showed a reduction in susceptibility.
On the usage of monoclonal Abs, the Delta, B.1.617.3, and variation showed a drop in neutralization. As a result, the office of the Assistant Secretary for Preparedness and Response halted the distribution of bamlanivimab and etesevimab as of June 25, 2021.
However, recent research demonstrated that bamlanivimab and etesevimab were effective against the majority of delta variant lineages. As a result of this data, they were given permission to utilize them again as of September 15, 2021.
The global impact of the delta variant
Understanding the features of each of the SARS-CoV-2 variants can help stop the COVID-19 pandemic from spreading. The S gene encodes the spike protein that binds with the host’s ACE-2 receptor and facilitates virus entrance into the host cell, according to the researchers. All vaccinations and neutralizing antibodies are directed against the S protein, and some treatments aim to stop the virus from replicating inside the host cell.
As of September 2021, the SARS-CoV-2 delta form had been reported in 162 countries on six continents. Vaccination and spontaneous infection are the most effective ways to combat the pandemic. In early 2021, vaccinations and a rigorous lockdown on international borders were implemented in the United States and the European Union.
Despite vaccination, a new wave of the delta variety spread over the world. This suggests that the new version may be immune to immunizations or antibodies that neutralize it.
The delta variant has a one-of-a-kind mutation.
SARS-CoV-2 and B.1.617.3, the two closest variants to delta, did not spread outside of India, despite being reported at the same time. A single unique mutation site, T478K, was discovered when the delta variant’s S gene mutation sites were compared to those of the other two variants. This mutation was discovered in the S gene’s crucial receptor binding motif (RBM). E156del and R158G are two further distinct mutations in the NTD of the S1 region found in the delta form.
The RBM amino acid sequences for the 10 SARS-CoV-2 variants that interacted directly with ACE-2 were aligned. Among the 21 possible contact sites, only six residues were discovered to have a common interaction site. In addition, the S gene’s ACE-2 binding residues were directly matched to the mutation sites of the variants.
The ACE-2 interacting residues and the ten variants showed a slight connection.
Conclusion
According to the current study, variations in the mutation sites of SARS-CoV-2 variants are to blame for the unique global outbreak of COVID-19. The delta form has an unique T478K mutation that may be responsible for its increased transmissibility, severity, and vaccination escape.
To avoid future outbreaks, a vaccine or neutralizing Ab against the delta variant must be produced.
Journal reference:
- Jhun, H. et al. (2021) “SARS-CoV-2 Delta (B.1.617.2) Variant: A Unique T478K Mutation in Receptor Binding Motif (RBM) of Spike Gene”, Immune Network, 21(5)
