Abstract

SARS-COV2 is originated from a closely related bat Coronavirus RaTG13 after gaining insertions by exchanged recombination with pangolin virus Pan_SL_COV_GD. SARS-COV2 uses its entry-point key residues in S1 protein to attach with ACE2 receptor to infect human. The evolution of SARS-COV2 could include its early entrance into human with defective entry-point residues but remained silent for very long time with slow mutation rate or recently with efficient entry-point residues but adapted quickly to evade human immune system with high mutation rate or recently through an intermediate host. RaTG13 shows 96.3% identity with SARS-COV2 genome of 29903 base implying that it substituted ~1106 nucleotides to become present-day virus. Analyzing nucleotide substitutions of eighty-three SARS-COV2 genome from December, 2019, we show that its mutation rate in human is as low as 36 nucleotides per year that would take approximately 30 years to emerge as SARS-COV2 from bat RaTG13. Furthermore, a critical entry-point residue 493Q that binds with K31 residue of ACE2 is evoluted from RaTG13 amino acid Y, which needs the code must be mutated twice with an intermediate virus carrying amino acid H (Y>H>Q). However, such an intermediate COV virus has not been identified in bat or pangolin. Taken together, absence of any evidence of silent presence of SARS-COV2 in human for a long time or very high mutation rate or an intermediate host or virus emphasizes that either such an intermediate host or virus must be still obscure in nature or the creation of SARS-COV2 artificially cannot be ruled out.

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