Evolutionary Perspective and Theories on the Possible Origin of SARS-CoV-2

Objective: From the currently available next-generation sequencing data, we have tried to analyze different theories on the origin of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and thereby to identify the origin of its intermediate host. Genome sequence-based phylogenetic analysis and multiple sequence alignment were performed. Methods: We used the Virus Pathogen Resource (ViPR) platform for phylogenetic analysis and the MUltiple Sequence Comparison by Log- Expectation (MUSCLE) algorithm for whole genome sequence alignment of SARS-CoV-2, severe acute respiratory syndrome coronavirus (SARS-CoV), BJ01, Middle East respiratory syndrome coronavirus (MERS-CoV), bat coronavirus RaTG13, and pangolin coronavirus. Results: From these two analyses, we have found that RaTG13 is the closest relative to SARS-CoV-2 and not the pangolin coronavirus in spite of having sequence homology-based similarity in the genes. Comparing the RNA-dependent RNA polymerase (RdRp) and interacting spike (S) protein that interacts directly with the host human angiotensin-converting enzyme 2 (hACE2), the bat coronavirus RaTG13 was found to be the closest relative to SARS-CoV-2. Through multiple sequence alignment of the amino acid sequences, we found the furin-like cleavage site RRARS only in SARS-CoV-2 at the junction of the two subunits S1/S2 of the spike protein. Conclusions: The possible zoonotic transfer that has happened in SARS-CoV-2 seems to not be from the pangolin, but RaTG13 remains closest relative to SARS-CoV-2. Further studies, such as systematic reviews of the literature and meta-analyses, are needed to reach a conclusion regarding the evolutionary trajectory of the SARS-CoV-2 outbreak.