Kreiser Topaz, Zaguri Dor, Sachdeva Shreya, Zamostiano Rachel, Mograbi Josef, Segal Daniel, Bacharach Eran, Gazit Ehud
The Shmunis School of Biomedicine and Cancer Research, Tel Aviv University, Tel Aviv 6997801, Israel.
Independent Researcher, Tel Aviv 6937940, Israel.
Pharmaceuticals (Basel). 2022 Mar 20;15(3):377. doi: 10.3390/ph15030377.
Controlling the infectivity of respiratory RNA viruses is critical, especially during the current SARS-CoV-2 pandemic. There is an unmet need for therapeutic agents that can reduce viral replication, preferably independent of the accumulation of viral mutations. Zinc ions have an apparent activity as modulators of intracellular viral RNA replication and thus, appear attractive in reducing viral RNA load and infectivity. However, the intracellular concentration of zinc is usually too low for achieving an optimal inhibitory effect. Various herbal polyphenols serve as excellent zinc ionophores with known antiviral properties. Here, we combined zinc picolinate with a collection of flavonoids, representing commonly used polyphenols. Copper was added to avoid ionic imbalance during treatment and to improve efficacy. Each component separately, as well as their combinations, did not interfere with the viability of cultured A549, H1299, or Vero cells in vitro as determined by MTT assay. The safe combinations were further evaluated to determine antiviral activity. Fluorescence-activated cell sorting and quantitative polymerase chain reaction were used to evaluate antiviral activity of the combinations. They revealed a remarkable (50-95%) decrease, in genome replication levels of a diverse group of respiratory RNA viruses, including the human coronavirus OC43 (HCoV-OC43; a betacoronavirus that causes the common cold), influenza A virus (IAV, strain A/Puerto Rico/8/34 H1N1), and human metapneumovirus (hMPV). Collectively, our results offer an orally bioavailable therapeutic approach that is non-toxic, naturally sourced, applicable to numerous RNA viruses, and potentially insensitive to new mutations and variants.
控制呼吸道RNA病毒的传染性至关重要，尤其是在当前的新冠疫情期间。对于能够减少病毒复制的治疗药物存在未满足的需求，最好是不依赖于病毒突变的积累。锌离子作为细胞内病毒RNA复制的调节剂具有明显活性，因此在降低病毒RNA载量和传染性方面显得很有吸引力。然而，细胞内锌的浓度通常过低，无法达到最佳抑制效果。各种草药多酚作为具有已知抗病毒特性的优秀锌离子载体。在这里，我们将吡啶甲酸锌与一系列黄酮类化合物结合，这些黄酮类化合物代表常用的多酚。添加铜是为了避免治疗过程中的离子失衡并提高疗效。通过MTT法测定发现，每种成分单独以及它们的组合在体外均不干扰培养的A549、H1299或Vero细胞的活力。对安全的组合进一步评估以确定抗病毒活性。使用荧光激活细胞分选和定量聚合酶链反应来评估组合的抗病毒活性。结果显示，包括人类冠状病毒OC43（HCoV-OC43；一种引起普通感冒的β冠状病毒）、甲型流感病毒（IAV，A/波多黎各/8/34 H1N1株）和人偏肺病毒（hMPV）在内的多种呼吸道RNA病毒的基因组复制水平显著下降（50%-95%）。总体而言，我们的研究结果提供了一种口服生物可利用的治疗方法，该方法无毒、天然来源、适用于多种RNA病毒，并且可能对新的突变和变体不敏感。
