Human Coronavirus Photodynamic Inactivation and In Silico Mechanisms Induced by Ga(III) vs. Zn(II) Phthalocyanines.

Photodynamic inactivation (PDI) is a relatively new approach for targeting viruses. Recently, PDI has been shown to be effective against various viral infections, with a low probability of resistance development. The study presents PDI towards the infectivity of human coronavirus (HCoV-OC43) at different stages of its propagation and through different mechanisms of action. Two tetra-methylpyridiloxy-substituted gallium and zinc phthalocyanines (GaPcMe and ZnPcMe), exposed to light from a 660 nm light-emitting diode (LED), were evaluated and showed a high potential against HcoV-OC43. The effect of PDI on extracellular virions and the stage of their adsorption was assessed using the finite dilution method and by determining changes in viral infectivity (Δlgs). The impact on the viral replicative cycle was assessed by inhibition of the cytopathic effect (CPE). The direct effect on virions was notable for both phthalocyanines, but was significantly more pronounced for ZnPcMe (Δlg = 4). A strong inhibitory effect on virus adsorption was observed for ZnPcMe (from Δlg = 3.5 to complete inhibition, Δlg = 5.0, depending on the irradiation time). Both GaPcMe and ZnPcMe demonstrate PDI at an early stage of the virus replication cycle. This is reflected in the high photoinactivation indices PII = 44.0 for ZnPcMe and PII = 23.3 for GaPcMe. The binding potential of GaPcMe and ZnPcMe toward viral and host protein targets was investigated using molecular docking and molecular dynamics (MD) simulations. The computational panel included HCoV-OC43 3CLpro (Nsp5, PDB 9PAM) and homologous SARS-CoV-2 proteins, namely Nsp5, Nsp12, M protein, S protein, as well as human ACE2. The docking results indicated that both phthalocyanines exhibit notable theoretical binding affinity toward these targets.