Avoiding Regions Symptomatic of Conformational and Functional Flexibility to Identify Antiviral Targets in Current and Future Coronaviruses

Rahaman, Jordon; Siltberg-Liberles, Jessica

Our approach utilizes genomic sequence data, which is readily available for viruses known to cause disease. However, because most viruses pose no major threat to their host, they pass by unnoticed leaving the majority of virus genome space uncharted. With the availability of costefficient genome sequencing technology, and recent developments in the field of viral metagenomics, large-scale identification of viral genome space is on the rise (Rosario and Breitbart 2011; Mokili et al. 2012) . By exploring viral diversity, critical components constituting a viral genus' fitness can be evaluated. Examples such as the common influenza virus illustrate the rapidity of viral gene mutation and in order to maintain immune protection, an annual flu vaccination is recommended. Underway efforts aim to generate broadly neutralizing vaccines whose design accounts for the genomic sequences of multiple types of influenza virus to eliminate frequent re-vaccination against the flu Ross 2011, 2012) . Development of broadly neutralizing vaccines often relies on the consensus or ancestral sequences of extant viral sequences in order to provide greater coverage for related viruses (Kesturu et al. 2006) . Unfortunately, consensus sequences can be misleading, and ancestral sequence reconstruction is error-prone for quickly diverging sequences (McCloskey et al. 2014 ). In addition, viruses with compact genomes often express proteins with structural disorder that may undergo structural transformations. Although these transformer proteins, like VP40 in Ebola, are masters at changing their structure, and thus expanding their functional repertoire as needed for the life cycle of the virus (Bornholdt et al. 2013) , flexible regions are potentially important in rewiring protein-protein interactions between the virus and its host (Le Breton et al. 2011; Ortiz et al. 2013; Gitlin et al. 2014) .