Low-Frequency ORF4b Variants in MERS-CoV Perturb PDE-Mediated IFN Antagonism at Catalytic H35/H37/H39, NLS K45, and Structural P95 Under Purifying Selection

This dataset presents a residue-resolution surveillance of MERS-CoV ORF4b, an accessory protein that suppresses type I interferon by degrading 2′-5′ oligoadenylates via its phosphodiesterase (PDE) activity. We specifically interrogate experimentally validated functional elements: Catalytic His-rich motif (H35, H37, H39, E38): essential for PDE enzymatic functionNuclear localization signal (NLS; residues 43 - 50): required for nuclear import and IRF3/7 antagonismRNase L interaction surface (residues 60 - 79): mediates substrate recognitionStructural proline P95: maintains loop conformation Across 587 global ORF4b sequences, all observed variants are low-frequency (<2.1%), non-gain-of-function, and predicted to mildly attenuate, not enhance, IFN suppression. No evidence of adaptive evolution toward increased immune evasion was detected. The data confirm strong purifying selection on ORF4b’s functional architecture. Files generated: Full gapped alignment (MERSCoV_ORF4b_aligned_padded.fasta)Variant subsets for key residues (H35, H37, H39, K45, P95)8 detailed functional reports (PDE core, NLS integrity, entropy, truncation, etc.)Summary interpretation for manuscript-ready useThis resource enables ongoing monitoring of MERS-CoV’s capacity for innate immune antagonism and supports anticipatory modeling of viral attenuation or stability. Study by: Tahir HB