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The SARS-CoV-2 RNA pseudoknot is a promising target for antiviral intervention, as it regulates the efficiency of $-$1 programmed ribosomal frameshifting ($-$1 PRF), a mechanism that is essential for viral protein synthesis. The pseudoknot represents a viral RNA sequence composed of helical stems that adopts two long-lived topologies, threaded and unthreaded. Ligand-induced distortion of this fold is thought to underlie the susceptibility of $-$1 PRF to small-molecule inhibitors. Resolving these distortions from unbiased molecular dynamics (MD) requires collective variables (CVs) that isolate the slowest dynamic modes of the RNA--ligand system from the high-frequency fluctuations. Here, we use spectral map (SM), a thermodynamics-driven machine-learning method, to learn such CVs directly from MD trajectories of the SARS-CoV-2 RNA pseudoknot in complex with the $-$1 PRF inhibitor merafloxacin and two related analogs. We examine both threaded and unthreaded pseudoknot topologies and consider the neutral and ionized ligand forms relevant at physiological pH. Free-energy landscapes show that ligand-induced destabilization is topology-selective: merafloxacin and its analogs destabilize the S2 stem in the threaded pseudoknot, whereas in the unthreaded pseudoknot, destabilization shifts to the S1 and S3 stems. We find that the zwitterionic form of merafloxacin uniquely imposes slow dynamics on the otherwise featureless unthreaded pseudoknot. Furthermore, the neutral and zwitterionic forms of merafloxacin differ qualitatively in their mechanisms within the same RNA topology. Overall, these results clarify how pseudoknot topology, ligand type, and protonation state shape the slow conformational dynamics of viral RNA and establish physiological protonation as an essential factor for modeling RNA-targeted drug action.