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

Rahaman, Jordon; Siltberg-Liberles, Jessica

It should be noted that, despite the low amount of disordered sites in most CoV proteins, several regions are not conserved in disorder propensity across all sequences, but sometimes the different predictors disagree as in the case of NSP8. Clade-specific disordered regions resulting from indel events suggest that they are not essential to the critical functions of the protein, but could cause gain-and-loss of interactions with its hosts. However, when disorder propensity is only mildly fading for a region that is present across the protein family, it may be important for the fundamental function of the protein. The virus structural proteins that interact to form the virion commonly include an envelope protein, a membrane protein, and a capsid protein that together form the machinery that encases, transports, and releases the virus. The interactions between the structural proteins are often regulated by conformational changes like VP40 in Ebola (Bornholdt et al. 2013 ) and Envelope protein from Dengue virus (Zheng et al. 2014 ). Conformational changes to another. It should also be noted that two MERS clade specific inserts around position 241 and toward the C-terminal are consistently predicted to be highly disordered. With inserts and changing structural dynamics between clades or viruses, the questions become 1) which sequence motif are displayed and 2) to what extent are these sequence motifs displayed?