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

Rahaman, Jordon; Siltberg-Liberles, Jessica

A recent large-scale study of structural disorder in >2,000 viral genomes in 41 viral families found the amount of disorder in different virus families varying from 2.9% to 23.1% (Pushker et al. 2013) . It was reported that Coronaviridae has very low disorder content (mean disorder 3.68%) (Pushker et al. 2013) . Coronaviridae contains two subfamilies: Coronavirinae and Torovirinae. SARS-CoV and MERS-CoV are part the Coronavirinae subfamily, from here on referred to as coronavirus (CoV). The lack of disorder is intriguing because it may be important for rewiring interactions between viral proteins and host proteins (Ortiz et al. 2013 ) and providing opportunities to acquire novel functional sequence motifs (Gitlin et al. 2014) . Structural disorder has also been proposed to be important for viral viability, enabling multifunctionality and vigor in response to changes in the environment (Xue et al. 2014) . Given the low fraction of structural disorder reported across Coronaviridae, we set out to investigate the conservation of structural disorder and secondary structure across CoV. Sites identified as conserved for structure and lacking disorder can be considered to be vulnerable and druggable in the proteomes of coronaviruses. The structural divergence capacity of these regions is limited, leaving a wider range of the present and emergent coronaviruses susceptible to the effects of potential broadly neutralizing anti-CoV therapies targeting these sites. We will refer to these sites as target sites.