Department of Anaesthesiology and Intensive Care, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany.
Medical Faculty, Institute of Medical Microbiology and Virology, University of Leipzig, 04103 Leipzig, Germany.
Viruses. 2022 Jun 14;14(6):1301. doi: 10.3390/v14061301.
Despite available vaccines, antibodies and antiviral agents, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic still continues to cause severe disease and death. Current treatment options are limited, and emerging new mutations are a challenge. Thus, novel treatments and measures for prevention of viral infections are urgently required. Photodynamic inactivation (PDI) is a potential treatment for infections by a broad variety of critical pathogens, including viruses. We explored the infectiousness of clinical SARS-CoV-2 isolates in Vero cell cultures after PDI-treatment, using the photosensitizer Tetrahydroporphyrin-tetratosylate (THPTS) and near-infrared light. Replication of viral RNA (qPCR), viral cytopathic effects (microscopy) and mitochondrial activity were assessed. PDI of virus suspension with 1 µM THPTS before infection resulted in a reduction of detectable viral RNA by 3 log levels at day 3 and 6 after infection to similar levels as in previously heat-inactivated virions (<99.9%; p < 0.05). Mitochondrial activity, which was significantly reduced by viral infection, was markedly increased by PDI to levels similar to uninfected cell cultures. When applying THPTS-based PDI after infection, a single treatment had a virus load-reducing effect only at a higher concentration (3 µM) and reduced cell viability in terms of PDI-induced toxicity. Repeated PDI with 0.3 µM THPTS every 4 h for 3 d after infection reduced the viral load by more than 99.9% (p < 0.05), while cell viability was maintained. Our data demonstrate that THPTS-based antiviral PDI might constitute a promising approach for inactivation of SARS-CoV-2. Further testing will demonstrate if THPTS is also suitable to reduce the viral load in vivo.
尽管有可用的疫苗、抗体和抗病毒药物，但严重急性呼吸综合征冠状病毒 2 型（SARS-CoV-2）大流行仍在继续导致严重疾病和死亡。目前的治疗选择有限，新出现的突变是一个挑战。因此，迫切需要新的治疗方法和预防病毒感染的措施。光动力灭活（PDI）是一种治疗多种关键病原体感染的潜在方法，包括病毒。我们使用光敏剂四氢卟啉四磺酸钠（THPTS）和近红外光，探索了 PDI 处理后临床 SARS-CoV-2 分离株在 Vero 细胞培养物中的传染性。通过 qPCR 评估病毒 RNA 的复制、病毒细胞病变效应（显微镜）和线粒体活性。感染前用 1µM THPTS 对病毒悬液进行 PDI 处理，可使感染后第 3 天和第 6 天可检测到的病毒 RNA 减少 3 个对数级，与先前热失活病毒颗粒相似（<99.9%；p<0.05）。病毒感染显著降低的线粒体活性通过 PDI 明显增加，达到与未感染细胞培养物相似的水平。在感染后应用基于 THPTS 的 PDI 时，只有在更高浓度（3µM）时单次处理才具有降低病毒载量的效果，并且 PDI 诱导的毒性会降低细胞活力。感染后每 4 小时用 0.3µM THPTS 重复 PDI 3 天，可使病毒载量减少 99.9%以上（p<0.05），同时保持细胞活力。我们的数据表明，基于 THPTS 的抗病毒 PDI 可能是一种有前途的 SARS-CoV-2 灭活方法。进一步的测试将证明 THPTS 是否也适合降低体内的病毒载量。
