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

Rahaman, Jordon; Siltberg-Liberles, Jessica

For regions with five or more consecutive sites that were 100% conserved in sequence across 1) all CoV or 2) across the MERS and SARS clades, the information of structural disorder prediction from IUPred and DISOPRED2 was used to identify all ungapped sites that were consistently predicted to have 100% conserved order. Next, the information of secondary structure prediction from PSIPRED and JPred was used to narrow down this list further by only including sites that are not changing their predicted secondary structure state for both predictors. Applying the aforementioned filters to the initial 10,000 sites resulted in one (1) region of five residues or more conserved across all CoV within the N-terminal domain of NSP12: DNQDL (table 4) . Interestingly, this region is in the vicinity of sites found important for nucleotidylating activity across the order Nidovirales (Lehmann et al. 2015) .