The anti-viral properties of a small (≈1 kDa), novel Ru(II) photo dynamic compound (PDC), referred to as TLD-1433 (Ruvidar™), are presented. TLD-1433 had previously been demonstrated to exert strong anti-bacterial and anti-cancer properties. We evaluated the capacity of TLD-1433 to inactivate several human pathogenic viruses. TLD-1433 that was not photo-activated was capable of effectively inactivating 50 % of influenza H1N1 virus (ID₅₀) at a concentration of 117 nM. After photo-activation, the ID₅₀ was reduced to 99 % (ID₉₉) was approximately 170 nM. Similarly, the ID₉₉ of photo-activated TLD-1433 was determined to range from about 20 to 120 nM for other tested enveloped viruses; specifically, a human coronavirus, herpes simplex virus, the poxvirus Vaccinia virus, and Zika virus. TLD-1433 also inactivated two tested non-enveloped viruses; specifically, adenovirus type 5 and mammalian orthoreovirus, but at considerably higher concentrations. Analyses of TLD-1433-treated membranes suggested that lipid peroxidation was a major contributor to enveloped virus inactivation. TLD-1433-mediated virus inactivation was temperature-dependent, with approximately 10-fold more efficient virucidal activity when viruses were treated at 37 °C than when treated at room temperature (∼22 °C). The presence of fetal bovine serum and virus solution turbidity reduced TLD-1433-mediated virucidal efficiency. Immunoblots of TLD-1433-treated human coronavirus indicated the treated spike protein remained particle-associated.

Photodynamic therapy (PDT) is an approved procedure using a photosensitizer (PS) activated by light to selectively destroy malignant/premalignant cells. Transition metal complexes, such as Ru(II)- and Os(II)-based PSs (Theralase Technologies Inc., Ontario. Canada), are activated in a wide range of wavelengths, are resistant to photobleaching and have a high singlet oxygen quantum yield and ability to produce cytotoxic reactive oxygen species (ROS). Their design allows fine-tuning of the photophysical and photochemical properties. They demonstrate Type I and II photoreactions, and some are activated in hypoxia. High PDT potency and activation under NIR light and even X-ray may provide an advantage over the approved PSs. Their ability to associate with transferrin (Tf) as an endogenous delivery system increases photobleaching resistance, ROS production, selective cellular uptake, and PDT efficacy in combination with a decreased systemic toxicity. This makes these PSs attractive for systemic therapy of recurrent/progressive cancers. Their PDT efficacy has been demonstrated in various in vitro and in vivo clinically relevant models. The unique properties of the mentioned PSs allow bypassing such limitations of PDT as low specific uptake ratio, insufficiently broad absorption band, and low efficacy in hypoxia. One of these PSs (TLD-1433) was successful against non-muscle invasive urinary bladder cancer unresponsive to contemporary anticancer therapies.

Infectious agents account for millions of deaths every year. The Herpes Simplex Viruses (HSVs) are large double-stranded DNA viruses that infect more than 90% of the human population and can establish life-long latency in human hosts. Currently, effective FDA approved anti-herpetic drugs include acyclovir and later-generation derivatives (valacyclovir and famciclovir), which inhibit viral DNA synthesis. In previous work, we demonstrated that the small molecule Ruvidar^® could inhibit numerous pathogenic human viruses when added to solutions of viruses both with and without light activation. In these experiments, we evaluated the ability of Ruvidar^® to restrict HSV-1 replication in Vero cells, both by itself and in combination with acyclovir and metformin in the absence of light activation to mimic deep tissue. Ruvidar^® successfully inhibited HSV-1 replication at significantly lower concentrations and more effectively than either acyclovir or metformin alone. We also discovered additive and synergistic anti-HSV-1 effects when combinational therapy was tested. Ruvidar^® also restricted HSV-1 replication in human U251 glioblastoma astrocytoma cells, remained highly effective against acyclovir-resistant HSV-1 mutants, and protected infected cells from virus-induced cytopathology.