Nanomolar concentrations of the photodynamic compound TLD-1433 effectively inactivate numerous human pathogenic viruses
Kevin M. Coombs,
Kathleen K.M. Glover,
Raquel Russell,
Pavel Kaspler,
Mark Roufaiel,
Drayson Graves,
Peter Pelka,
Darwyn Kobasa,
Roger DuMoulin-White,
Arkady Mandel
Affiliations
Kevin M. Coombs
Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, R3E 0J9, Canada; Manitoba Centre for Proteomics and Systems Biology, University of Manitoba, Winnipeg, Manitoba, R3E 3P4, Canada; Corresponding author. Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, R3E 0J9, Canada.
Kathleen K.M. Glover
Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, R3E 0J9, Canada; Manitoba Centre for Proteomics and Systems Biology, University of Manitoba, Winnipeg, Manitoba, R3E 3P4, Canada
Raquel Russell
Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, R3E 0J9, Canada; Manitoba Centre for Proteomics and Systems Biology, University of Manitoba, Winnipeg, Manitoba, R3E 3P4, Canada
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.
