DOI: 10.5281/zenodo.18236097
title: Defining the Upper Bound of MERS-CoV ORF4a/4b-Mediated Interferon Antagonism Through Combinatorial Sequence Instantiation

description: This dataset presents a set of computationally derived sequence instantiations designed to probe the functional limits of MERS-CoV accessory proteins ORF4a and ORF4b in type I interferon antagonism. These constructs are not observed in nature and do not represent predicted evolutionary trajectories. Instead, they define the upper boundary of plausible molecular variation, what we term as "the evolutionary ceiling based on structural and functional constraints" inferred from global genomic surveillance (Bhatti 2026; DOIs: 10.5281/zenodo.18231464, 10.5281/zenodo.18233185).

By mapping where variation could enhance immune evasion, but does not occur in >1,000 circulating genomes, this work turns absence into evidence: the persistent conservation of key residues (Y14, L15, P18 in ORF4a; H35, H37, H39, K45, P95 in ORF4b) explains why MERS-CoV remains a spillover-limited pathogen despite decades of zoonotic circulation.

The dataset enables:

Sentinel-based early warning: Rule-defined alerts (e.g., “if Y14W detected → immediate escalation”)Non-alarmist threat modeling: A grounded alternative to speculative scenariosPolicy-ready genomics: Bridging sequence data with public health preparednessBoundary mapping: Distinguishing what is possible from what is probable

Scientific Positioning:This work emphasizes on risk assessor and boundary-mapper. All instantiations are in silico hypotheses intended solely for defensive surveillance logic.

Access Policy:Full sequence instantiations are not publicly distributed. They are available upon controlled request to qualified researchers via institutional review, in alignment with responsible science principles. The public record includes only residue-level design logic and impact assessment.

Included Files:

GoF-MERS-01_ORF4a.fasta → Boundary instantiation (ORF4a Y14W)GoF-MERS-02_ORF4a.fasta → Boundary instantiation (ORF4a L15F)GoF-MERS-03_ORF4a.fasta → Boundary instantiation (ORF4a Y14W+L15F)GoF-MERS-04_ORF4b.fasta → Boundary instantiation (ORF4b catalytic pocket variant)GoF-MERS-05_ORF4b.fasta → Boundary instantiation (ORF4b NLS/loop variant)GoF-MERS-06_ORF4a_ORF4b.fasta → Combined boundary scenarioGoF_Impact_Assessment.txt → Functional impact rationaleMERS_CoV_ORF4a_ORF4b_GoF_Scenarios_Summary.txt → Scientific and policy context

 

Surveillance study conducted by: Tahir HB for upcoming preprint.
description: DURC Statement:

This dataset describes in silico synthetic genotypes of MERS-CoV accessory proteins ORF4a and ORF4b, designed solely to define the theoretical boundaries of viral immune evasion potential. These sequences are not observed in nature, are not constructed experimentally, and are not intended for synthesis or functional testing outside approved biosecurity frameworks. The work is conducted under the principles of responsible science and proactive risk assessment, with the goal of enhancing global surveillance capacity, not enabling misuse. Any future experimental validation must comply with institutional biosafety and national regulatory guidelines.

Tahir HB.