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

doi:10.1016/j.heliyon.2024.e32140

Nanomolar concentrations of the photodynamic compound TLD-1433 effectively inactivate numerous human pathogenic viruses

Heliyon. 2024 May 29;10(11):e32140. doi: 10.1016/j.heliyon.2024.e32140. eCollection 2024 Jun 15.

Authors

Kevin M Coombs^{1

2}, Kathleen K M Glover^{1

2}, Raquel Russell^{1

2}, Pavel Kaspler³, Mark Roufaiel³, Drayson Graves⁴, Peter Pelka⁴, Darwyn Kobasa⁵, Roger DuMoulin-White³, Arkady Mandel³

Affiliations

¹ Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, R3E 0J9, Canada.
² Manitoba Centre for Proteomics and Systems Biology, University of Manitoba, Winnipeg, Manitoba, R3E 3P4, Canada.
³ Theralase® Technologies Inc., 41 Hollinger Road, Toronto, Ontario, M4B 3G4, Canada.
⁴ Department of Microbiology, University of Manitoba, Winnipeg, Manitoba, R3T 2N2, Canada.
⁵ Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, R3E 3R2, Canada.

Abstract

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 <10 nM. The dose of photo-activated TLD-1433 needed to reduce H1N1 infectivity >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.

Keywords: Antivirals; Lipid envelope; Photodynamic therapy; Ruvidar™; TLD-1433.