This manuscript describes an effective and rapid three-component synthesis of a novel series of spiro-acridine derivatives by integrating the pharmacologically dynamic hydantoin–phenytoin as the prime synthetic equivalent. The process was accelerated by Fe₃O₄@TiO₂-PTA magnetic nanoparticles (MNPs), which acted as the heterogeneous catalytic system, under ultrasonic conditions. The reaction was performed in the green PEG-200 solvent under aerophilic conditions to obtain products with excellent yields. The characteristics of the synthesized magnetic nano-catalysts were corroborated through powder X-ray diffraction (PXRD), field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDAX), FT-IR, and VSM techniques. In addition, the structures of the synthesized compounds were ascertained on the basis of elemental analyses and spectro-analytical data (¹H NMR, ¹³C NMR, and mass spectrometry). High yields, smaller E-factor, considerable atom economy, easy recovery, and recyclability of the catalyst and solvent are the captivating features of the developed protocol. Moreover, in view of the ongoing global research on COVID-19, herein, we tried to identify the potential sites of the synthesized moiety that can suitably fit the receptor sites of the main protease of SARS-CoV-2 (SARS-CoV-2 M^pro).