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.
摘要:
一个小的抗病毒特性(≈1kDa),新型Ru(II)光动力化合物(PDC),称为TLD-1433(Ruvidar™),被呈现。TLD-1433先前已被证明具有强大的抗菌和抗癌特性。我们评估了TLD-1433灭活几种人类致病病毒的能力。未光活化的TLD-1433能够在117nM的浓度下有效灭活50%的流感H1N1病毒(ID50)。照片激活后,ID50降低至<10nM。降低H1N1感染性>99%(ID99)所需的光活化TLD-1433的剂量约为170nM。同样,对于其他测试的包膜病毒,光活化的TLD-1433的ID99被确定为约20至120nM;特别是,一种人类冠状病毒,单纯疱疹病毒,痘病毒痘苗病毒,和寨卡病毒。TLD-1433还灭活了两种测试的无包膜病毒;特别是,腺病毒5型和哺乳动物正病毒,但是浓度要高得多。对TLD-1433处理的膜的分析表明,脂质过氧化是包膜病毒灭活的主要原因。TLD-1433介导的病毒灭活是温度依赖性的,当病毒在37°C处理时,比在室温(~22°C)处理时,具有大约10倍的有效杀病毒活性。胎牛血清和病毒溶液浊度的存在降低了TLD-1433介导的杀病毒效率。TLD-1433处理的人冠状病毒的免疫印迹表明处理的刺突蛋白保持颗粒相关。