**4. Mutations**

RNA viruses must establish an equilibrium between the adaptability to new environmental circumstances or the necessity to preserve the intact and replicative genome to ensure survival and propagation for the host cells. Various virus families with the biggest and most complex replicating RNA genomes identified, up to 32 kb of positive RNA, such as coronaviruses, can achieve these objectives. CoVs, including (MHV) and SARS-CoV, express 3 to 5′ of exoribonuclease (ExoN) activity in nsp14. The exoN genetic inactivation of alanine replacement with retained active DE-D Residues in Engineered SARS-CoV and MHV Genomes leads to viable mutants, which display 15 to 20 times higher mutation rates and up to 18 times higher than those endured for other RNA fidelity mutants. Nsp14-ExoN, therefore, is important for the fidelity of the replication and possibly acts as a direct mediator or regulator for a more complex RNA proof-reader, an exceptional process in RNA virus biology. The removal of nsp14-mediated proofreading mechanisms will have significant consequences for our interpretation of RNA virus evolution and will also provide a robust model to research the correlation between fidelity,



#### *SARS-CoV-2 and Coronavirus Ancestors under a Molecular Scope DOI: http://dx.doi.org/10.5772/intechopen.95102*

#### **Table 2.**

*Mutations of SARS-CoV-2 strains found throughout the whole genome. The number in the parentheses shows where amino acid is found in its protein [21].*

diversity and pathogenesis [48–52]. COVID-19 is very related to SARS-CoV Middle East Respiratory Syndrome (MERS). Yet another human attack by coronaviruses. A research attempted to explore potential changes/developments in the 'spike protein' element that enables the virus to bind to cell receptor(s) and in the silicon design and discovery of B epitopes in which antibody synthesis is used to neutralize and block this connection. The findings show that this protein varies constantly between

#### *Cell Interaction - Molecular and Immunological Basis for Disease Management*



#### *Cell Interaction - Molecular and Immunological Basis for Disease Management*



#### **Table 3.**

*Coding mutation list detected in SARS-CoV-2 genomes [57].*


#### **Table 4.**

*Non-coding mutation list detected in SARS-CoV-2 genomes [57].*

the sequences of proteins obtained worldwide. Some B epitopes (part of an antigen molecule to which an antibody attaches itself), 177-MDLEGKQGNFKNL-189-555- SNKKFLPF-562-656 -VNSYECDIPI-666, 1035- GQSKRVDFC-1043, from the Cons sequence constructed from global protein sequences released between 11 Feb and 06 April, have been found to meet most of the criteria required for real wet application [53]. SARS-CoV is well suited to cultural development and does not seem to be selected in humans. It was also assessed that, in late October 2002, the alleged root of the SARS outbreak was consistent with a previous report of case use from China. The higher structural and antigenic sequence divergence and significant deletions within 3 '– of much of the viral genome indicate that some selection pressures conflict along with the functional structure of these confirmed and suspected ORFs [54]. In three regions the SARS and SARSr of bats-CoVs are largely different: S, ORF8 and ORF3. SARSr-CoVs bats share high sequence with the SARS- COV in the S2 but are highly different in the S1 region. However, bat MERSr-CoVs bats and human and camel MERS-CoVs share similar genomics but are significantly different from their genomic sequences [7]. Comparison of COVID-19, SARS-CoV and MERS-CoV genome sequence showed that COVID-19 has better sequence similarity with SARS-CoV compared to MERS CoV. Nevertheless, the COVID-19 amino acid sequence differed from the other coronavirus in specific areas of 1ab polyprotein and surface glycoprotein or S-protein [31]. Considering the high rate of mutation that characterizes RNA viruses, it is clear that several more mutations will emerge in the viral genome to monitor the spread of SARS-CoV-2 knowing that also their mutations rate are lower than other RNA viruses due to their proofreading activity described above [55, 56](**Tables 2**–**4**).
