A model to rank viruses based on their probability to cause the next pandemic.

The greater the sequence similarity between the receptor binding domain (RBD) or the host entry receptors (HER) of a zoonotic virus to the RBD or the HER respectively of human infective viruses, the greater the probability of a species jump. The RBD as well as the HER for 106 zoonotic viruses, 46 human infective viruses and 54 human/animal HERs’ were obtained from the literature and/or from the UNIPROT database. Ten training virus pairs whose vaccines were known to be cross-reactive (for each pair) were BLASTed to find similarities. The BLAST results for each virus pair were taken as input parameters to formulate an equation whose output; the cross reactivity value (CV); was indicative of the extent of cross reactivity between the virus pair. A CV < 1 indicated that the RBDs’ of test virus pairs, or entry receptor pairs were similar and hence would produce cross-reactive antibodies. The CV between each zoonotic virus and 46 human infective viruses was determined. For those pairs where the CV < 1, a Virus Component Number (VCN) was calculated using affinity and avidity values. Similarly, a Receptor Component Number (RCN) was obtained using BLAST HER similarity scores for each zoonotic virus receptors and the receptors for 57 human infective viruses. Adding the VCN and RCN for each virus resulted in a Total Score that was ranked from greatest to least. Viruses that are highly prevalent in the human population were excluded, and the top ranked 10 emerging viruses with case fatality rates of > 50% were selected. Our model can predict which existing vaccines are cross reactive against the emerging viruses, hence pre-empting and preventing pandemic genesis by vaccinating geographically susceptible populations. Additionally, the list is small enough that resources can be mustered to research, manufacture and stockpile vaccines and/or antiviral drugs against these ten viruses. The model is a much needed valuable tool in the as yet sparse toolkit of predicting and preventing pandemics caused by lethal zoonotic viruses.