The viruses then mutate to become the B117 variant which is common in the UK and it is a substitution between the N501Y, another variant is the B1351, the P1, and the Delta variants. In my next posts, I will explain these variants but it is important to know what causes these variants to be different. - (my previous post)
In my previous post, we started discussing the variants of the SARS-CoV2 virus, and I started talking about the D614G variant and explained its component, and replication. I explained that the S-protein is the primary protein of the virus. I mentioned that it is the concerning protein for vaccine creation, and builds immune response against it. The virus also has other materials which are the Envelope, Nucleo capsid, and single-stranded RNA. The Spike protein (S-protein) will bind to the ACE-2 protein which is a protein expressed in our alveoli. Besides the ACE-2 Protein is the TMPRSS2 which cleaves the viral protein allowing the virus gets into the cell through a receptor-mediated endocytosis. Inside the cell, the virus releases the single-stranded RNA into the cytoplasm, allowing it to interact with the ribosomes both free-moving ribosomes and the ones attached to the endoplasmic reticulum. Different genes on the RNA strands, interact with ribosomes to give proteins that will be needed to create new RNAs for the virus such as RNA Polymerases, Replicases, Proteases, envelope proteins, nucleocapsid proteins, hemaglutinin esterase proteins, and spike proteins. The SARS-CoV2 variants experience mutations in the Spike protein genes in the strand and this alters the look of the spike protein increasing the viral entry of the Virus into the cell as well as evading the immune system. When the proteins are made, they are transported to the Golgi Apparatus where they get into a vesicle where the virus starts to form. The Golgi membrane fuses with the cell membrane where the virus is released into the cell to infect other cells while destroying the cell.1, 2,3.
B.1.1.7 is a nutation of the SARS-CoV2 virus, and it is common in the UK, and becoming the dominant variant gradually. B.1.3.5.1 variant is another variant of the SARS-CoV2 Virus that is common in South Africa, so it can be regarded as the South African Variant, another variant is the P1 variant which originated in Brazil, the Delta Variant.
Looking at the B.1.1.7 variant, in the Spike Protein Gene mutation occurs in N501Y where there is a change in the spike protein which is made up of the S1, S2, and the Receptor binding domain.4 And in N501Y, there is a change in the receptor binding domain of the spike protein. This increases the entry binding and endocytosis of the virus into the cell from the ACE-2 protein. With increase in viral entry, then there will be more replication of the viruses already in the cell, increasing the infection of the virus in the cells where it is localized which is the lungs, and this means that there is more viral load, and the virus can be expelled from the host, to infect other people as the transmission of the virus is increased. This mutation os also present in the B.1.3.5.1 variant and the P.1 variant.5,6, 7 Another mutation in the Spike gene is in the deleting of the amino acid ΔH69-V70 which changes the S1 and S2 which would mean that previous antibodies that were able to attack previous strain will not be to attack the new variant as a result of the changes in the Spike protein. This will mean that the virus can evade neutralizing antibodies that would have neutralized previous strain but this doesn't mean they will be able to bypass the memory T-Cells if the patient has been vaccinated of the previous strain because the changes in the S1 and S2 isn't much to differ much from the previous strain.8, 9, 7.
At the 618th amino acid of the S protein there is a substitution between P and H (P618H). This mutation changes structure in the S1 and S2 peptide of the S protein which will the activity of cleavage with TMPRSS2 and the Spike protein (furin cleavage sites), thereby increasing viral entry into the cell. 10, 11 In the B.1.3.5.1 and the P.1 variant has the E484K mutation. There is a substition in the 484th amino acid which occurs at the receptor binding motif which is in the receptor binding domain. It increases the interacton of the ACE-2 protein, which will allow more entry into the cell, which will increase reproduction, the increase the viral load.12, 13
The B.1.1.7 is the Alpha variant, the B.1.3.5.1 is teh Beta variant, the P1 is the Gamma variant. In my next post, I will explain extensively the Delta variant, which is another mutation of the D614G variant. Then we will look at the vaccine efficacies.
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