In this context, we evaluated the photodynamic effects of four cationic tetra-(pyridyl)porphyrins against Vaccinia virus Western Reserve (VACV WR) and Monkeypox virus (MPXV). The porphyrins were initially analyzed for cytotoxicity to Vero cells by MTT assay and the maximal non-cytotoxic concentrations were used in virucidal assays. For virucidal assays, VACV-WR (107.5 TCID50/mL) and MPXV suspensions (106.97 TCID50/mL) were incubated with porphyrins, exposed (or not) to white light conditions at 45 min. Aliquots of virus suspensions were collected and quantitated, comparing the titers with those of virus suspensions not exposed to porphyrins and/or to light. Porphyrins 4-PtTPyP, 3-H2TMeP and 4-H2TMeP exhibited light-dependent activity and completely inactivated VACV-WR and MPXV after 5, 30 and 45 min of light exposure, respectively. In contrast, derivative 3-PtTPyP inactivated the viruses even in the absence of white light exposure, a light-independent virucidal activity. Virucidal assays were performed in the presence/absence of ROS scavengers. Ascorbic acid (AA) was the only capable of completely inhibiting photodynamic inactivation by the three porphyrins. This indicates a type II photodynamic mechanism by singlet oxygen (1O2). These results demonstrated photodynamic inactivation of poxviruses by tetra-cationic porphyrins, supporting their potential use - especially 4-PtTPyP – for virus inactivation in many applications. These results also pave the way for testing porphyrin in PDT of poxvirus-induced cutaneous lesions. In addition, our data validated the use of VACV as a in vitro model for targeted MPXV virucidal testing.
Photodynamic inactivation (PDI) has emerged as a promising antiviral strategy, especially in the context of newly identified viruses that pose ongoing threats to human and animal health (Wiehe et al., 2019). This scenario is further complex by the difficulty in identifying effective antiviral drugs, the emergence of drug-induced viral resistance and the biological damage caused by conventional chemical virucides (Irwin et al., 2016). PDI, either alone or in combination with antiviral drugs, offers a number of potential applications. These include the treatment of cutaneous lesions caused by epitheliotropic viruses, such herpes simplex virus (HSV) (Felber et al., 1973), human papillomavirus (HPV) (Hu et al., 2018) and vaccinia virus (Orthopoxvirus vaccinia, VACV) (Basso et al., 2019).
Porphyrins are photoactive compounds that absorb and transfer light energy to oxygen molecules, generating reactive oxygen species (ROS) and singlet oxygen (1O2) (Abrahamse and Hamblin, 2016). Once generated, ROS may alter biological molecules and cellular processes, promoting apoptosis or inactivating microorganisms. Evidence indicates that singlet oxygen (1O2) is the main radical responsible for the photodynamic inactivation of viruses (Costa et al., 2013; Davies, 2003). Due to its high reactivity and short half-life, singlet oxygen damages nearby molecules
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