Raekiansyah Muhareva, Ngwe Tun Mya Myat, Ang Alexandra, Lee Alexandra, Macalino Stephani Joy, Billones Junie, Takamatsu Yuki, Urano Takeshi, Murao Lyre Anni E, Quiming Noel, Morita Kouichi, Carrillo Maria Constancia
Department of Tropical Viral Vaccine Development, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan.
Department of Virology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan.
Pathogens. 2025 Aug 19;14(8):820. doi: 10.3390/pathogens14080820.
Natural products possess a wide range of biological and biochemical potentials, with plant-derived compounds being significant sources for discovering new drugs. In this study, extracts of and prepared with different solvents were tested for their antiviral activity against the original SARS-CoV-2 Wuhan strain and its variants using plaque assay, quantitative real time RT-PCR, and immunofluorescence assay (IFA). Our results showed that at their maximum non-toxic concentrations, Vitex-Dichloromethane (DCM) and Macaranga extracts significantly inhibited SARS-CoV-2 Wuhan strain growth in Vero E6 cells, showing a 5-log reduction in plaque assay and confirmed by IFA. Meanwhile, Vitex-Hexane showed moderate activity with a 2-log decrease. The inhibition was shown in a dose-dependent manner. The antiviral efficacy of these extracts was further demonstrated against various SARS-CoV-2 variants including Alpha, Beta, Delta, and Omicron. Both Vitex-DCM and Macaranga showed strong virucidal activity. In addition, Vitex-DCM and Macaranga inhibited the transcriptional activity of purified SARS-CoV-2 RdRp, indicating that RdRp inhibition may contribute to viral suppression as shown at the post-infection stage. Furthermore, combining Vitex-DCM or Macaranga with remdesivir showed a synergistic effect against SARS-CoV-2. These results suggest that and extracts are promising candidates for anti-SARS-CoV-2 treatments. Their synergy with remdesivir also underscores the potential of drug combinations in fighting SARS-CoV-2 and preventing the emergence of mutant variants.
天然产物具有广泛的生物学和生物化学潜力,植物衍生化合物是发现新药的重要来源。在本研究中,使用空斑试验、定量实时RT-PCR和免疫荧光试验(IFA),测试了用不同溶剂制备的牡荆属植物和血桐属植物提取物对原始SARS-CoV-2武汉毒株及其变体的抗病毒活性。我们的结果表明,在其最大无毒浓度下,牡荆属植物-二氯甲烷(DCM)和血桐属植物提取物显著抑制了Vero E6细胞中SARS-CoV-2武汉毒株的生长,在空斑试验中显示出5个对数级的减少,并通过IFA得到证实。同时,牡荆属植物-己烷显示出中等活性,减少了2个对数级。抑制作用呈剂量依赖性。这些提取物对包括阿尔法、贝塔、德尔塔和奥密克戎在内的各种SARS-CoV-2变体的抗病毒效果进一步得到证明。牡荆属植物-DCM和血桐属植物均显示出强大的杀病毒活性。此外,牡荆属植物-DCM和血桐属植物抑制了纯化的SARS-CoV-2 RdRp的转录活性,表明RdRp抑制可能在感染后阶段对病毒抑制起作用。此外,将牡荆属植物-DCM或血桐属植物与瑞德西韦联合使用对SARS-CoV-2显示出协同作用。这些结果表明,牡荆属植物和血桐属植物提取物是抗SARS-CoV-2治疗的有前途的候选物。它们与瑞德西韦的协同作用也突出了药物联合在对抗SARS-CoV-2和防止突变变体出现方面的潜力。