**5. Pathogenesis**

The structural proteins of this virion has specific roles for virus adhesion and invasion. The S glycoprotein mediates the viral particle's entrance phases, which include adhesion to the host cell membrane and fusion. S protein is formed as a homotrimer and inserted in numerous copies into the virion membrane, giving it a crown-like appearance. Many viruses utilize these similar glycoproteins for host entry including HIV-1, Ebola virus, and avian influenza viruses. This is split into two subunits: extracellular and transmembrane in infected cells (that is, the cleavage happens before the virus is released from the cell that generates it). Similarly, some coronaviruses break their S protein into S1 and S2 subunits during biosynthesis in infected cells, whereas other coronaviruses cleave their S protein only when they reach the next host cell. SARS- CoV-2 and MERS- CoV, come under the first category: its S protein is cleaved in virus-producing cells by proprotein convertases such as furin [19, 20]. As a result, the mature virion's S protein is made up of two non-covalently linked subunits: the S1 subunit binds ACE2 and the S2 subunit fixes the S protein to

the membrane. The S2 subunit also contains a fusion peptide and other machinery required to promote membrane fusion during new cell infection.

Receptor interaction by viral entry glycoproteins, generally in conjunction with other triggers, causes substantial conformational changes in both subunits, bringing the viral and cellular membranes together and eventually forming a fusion hole that allows the viral DNA to access the cell cytoplasm. The cleavage of a second site internal to the S2 subunit, known as the 'S2′ site, 'is one such trigger for SARS-CoV-2. The virus exposes the S2′ location by engaging ACE2. Cleavage of the S2′ site by an enzyme called transmembrane protease, serine 2 (TMPRSS2) [21–23] at the cell surface or by cathepsin L in the endosomal compartment releases the fusion peptide, beginning fusion pore development. Because the viral genome requires access to the cytoplasm and can only do so when this hole develops and the viral and cell membranes merge perfectly, where each step of the procedure is essential.

### **6. Evolution of viral variants**

Viruses are complex molecular structures with simple-looking morphology. They are just single-cell microorganisms containing genetic material either DNA or RNA [1]. That genetic material is made up of molecules that can be represented as a series of deoxy-ribonucleotides in the form of A = T (DNA), A = U (RNA), and G = C. Each part of this code contains instructions for how to make one specific protein that allows the virus to function. A virus has one goal that is, to make more of itself. But because it's not so simple, it cannot do that on its own. So, it uses a host. Every time a virus infects a person, it uses its cells to make copies of itself replicating this complex code again and again [1, 24]. But eventually, it makes a mistake, sometimes it deletes or adds a letter. Sometimes it flips them around. This mistake is called a mutation, which changes the instructions for making a virus. This slightly altered virus is a variant. Since viruses are constantly going through this copying process, it's normal for them to change over time [2, 25]. Most of the time mutations are harmless or even make the virus weaker, and they quietly disappear without making any notable difference. But when a series of mutations occur it gives the virus a slight edge over us. If a particular set of mutations makes a variant more successful, it might become more prominent than others and that's when it gets noticed. That is how the scientists started to notice SARS CoV2, back in September of 2020 [3, 4]. oronaviruses are covered in spike proteins that they use to bind with and infect human cells. The thing is, that binding is not a perfect fit. So, it does not always get past the cell's defenses. But the B.1.1.7 variant, which scientists later renamed the "Alpha" variant, has multiple mutations on the spike protein: Mutations that make it easier for the virus to bind with cells [5, 6, 26],help make the virus more transmissible. Which led it to become a dominant strain in many places around the world. But SARS CoV2 has been mutating all along. It's important to remember that a virus does not make active decisions. It creates strategy within the cells [17]. Mutations are random errors. But the longer a virus is around, the more people it infects, the more it will change and the more those changes accumulate and the virus evolves into something more dangerous. Alpha, Beta, Gamma, Omicron, and Delta are five variants considered as "variants of concern" by the W.H.O. All have mutations on the spike protein [2–4]. Delta, the most recent addition to this list, has been referred to as a "double mutant," because, while it has many different mutations, it has two significant mutations (L452R & E484Q ). These two mutations seem to make the virus more transmissible. Variant strains of the

#### *Perspective Chapter: Tracking Trails of SARS CoV-2 – Variants to Therapy DOI: http://dx.doi.org/10.5772/intechopen.106472*

virus make it easier for the virus to re-infect people who have already had Covid-19, meaning that variants may have evolved to dodge natural immune responses [17, 27]. The Omicron variant of COVID-19 is spreading more rapidly in comparison to other strains because it has more mutations majority of them on the spike proteins. The new omicron variant BA-2 appears to be about 50% more transmissible in comparison to the original omicron BA-1 and causes same severity of disease [2, 3]. BA-1 strain of omicron is more infectious in younger people and according to reports several people have been infected with omicron BA-1 and within a month infection with omicron BA-2. It appeared that this version of omicron was either highly infectious that it could overcome vaccine load or previous infection immunity, or it can evade immunity due to the mutation that it has evolved with [5, 27]. It was also more contagious compared to the Delta variants, as it quickly became the dominant strain in the US. W.H.O said it expects that people can spread omicron even if they are vaccinated or do not have symptoms [3, 6, 26]. Viruses multiply by copying their genomes over and over, but as an old photocopier, these copies are not always perfect. Each of these imperfect copies is a variant. Normally the imperfections or mutations do not change how the virus behaves and they can often make it less successful than the original strain [25, 28]. But very rarely mutations can change the virus in some important ways. The more a virus is allowed to replicate unchecked, the more chance it has to accumulate these rare beneficial mutations [2, 18]. That can occur when viruses are allowed to spread quickly through a population, or if they encounter an immune compromised host.
