**5. Evolution and origin**

Most SARS-CoV strains are derived from bats. SARS-CoV bat is a probable progenitor for SARS – CoV that is contagious to humans and civets, and thus it is important to study ACE2 receptor for monitoring origins of SARS-CoV and avoiding and controlling the outbreak. Though palm civets were involved in SARS emergence, most early MERS index cases had contact with dromedary camels. Indeed, the MERS-CoV strains separated from camels were nearly matching to those from humans [7]. The virus shares 96% of its genetic material with a virus detected from a bat found in a cave in Yunnan in China. A persuasive argument that it comes from bats but there is a critical alteration. The coronaviral spike proteins have a unit called a receptor-binding domain that is essential to the successful entry of human cells. Especially powerful is the SARS-CoV-2 binding domain and it varies from the bat virus Yunnan which appears to not affect human. Another Complicating matter, a scaly anteater called the pangolin with a coronavirus which was almost similar to the human version with a receptor-binding domain. However, the majority of the coronavirus was genetically identical just 90%, and some researchers do not believe that pangolin was the intermediary. It is difficult to draw a family tree since both mutations and recombinations are involved [58–60]. An article identifies and uses a machine learning-based alignment-free approach to identify a COVID-19 intrinsic genomic signature for an ultra-fast, scalable, and extremely precise classification of all COVID-19 virus genomes. The technique presented incorporates supervised machine learning with MLDSP for genome analysis, improved by a machine learning component decision tree approach and a Spearman-leading correlation coefficient analysis of tests. These methods are used to examine a broad collection of more than 61.8 million bp, including the 29 COVID-19 virus sequences on 27 January 2020, with over 5,000 unique viral genomic sequences. The findings endorse a bat hypothesis and the COVID-19 virus is classed under Betacoronavirus as the Sarbecovirus. Without any advanced biological expertise, training or genome annotations, our method achieves a 100% precise classification of the COVID-19 virus sequences, and determines the most important relationships between more than 5000 genomes in minutes, from the beginning on, with the sole use of raw DNA sequence details [61]. In a recent research, they have developed a phylogenetic tree, including other members of coronaviridae including Bat coronavirus (BCoV) and extreme acute respiratory 2019 disease, taking advantage of all of the available genomic knowledge. The closest BCoV sequence, with a 96,2% sequence 2019 SARS-CoV2 identity, confirm that all available genomes of the sequence are of zoonotic origin. We have confirmed the high sequence similarity (> 99%) among all available genomes. Given the low 2019 SARS-CoV2 heterogeneity, at least two genomic hyper various hotspots were identified, including one of the Serine/Leucine variations in viral ORF8 Protein encoded, can be detected [62]. (**Figures 6** and **7**) In the study a Malayan pangolinisolated coronavirus showed 100%, 98.6%, 97.8% and 90.7% SARS-CoV-2 amino acid identity in genes E, M, N, and S respectively. Particularly in the S protein of

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

**Figure 6.**

*A coronavirus phylogenetic tree based on full-length genome sequences. Both complete coronavirus genome sequences have been obtained from RefSeq, the NCBI reference sequence database [5].*

Pangolin-CoV, the receptor-binding domain is nearly the same as the SARS-CoV-2 with vital one-amino acid alteration. Results of comparative genomic analysis indicate that SARS-CoV-2 may have been the result of a Pangolin-CoV-like virus recombination with a Bat-CoV-RaTG13 virus [63].
