The methods and compositions provided herein, relate in part, to the discovery of conserved interactions between amino acid residues in all proteins encoded by SARS-CoV-related viruses. Accordingly, pairs and networks of residue variants that exhibited statistically high frequencies of covariance with each other can be used as a new computational approach (Covariance-based Phylogeny Analysis) for understanding viral evolution and adaptation. Provided herein is evidence that the evolutionary processes that converted a bat virus into a human pathogen occurred through recombination with other viruses in combination with new adaptive mutations important for entry into human cells.
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