Evaluating the antiviral efficacy and specificity of chlorogenic acid and related herbal extracts against SARS-CoV-2 variants via spike protein binding intervention

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus infect the respiratory tract through surface proteins, causing similar symptoms. Since the onset of the COVID-19 pandemic, both viruses have posed significant ongoing global health threats. Like the influenza virus, SARS-CoV-2 evolves into variants that can reduce vaccine efficacy. Thus, herbal medicines are being explored as supplementary options to enhance protection against these infections. This study aimed to investigate the therapeutic potential of chlorogenic acid (3-CQA) and related extracts from green coffee beans and <i>Echinacea purpurea</i> against SARS-CoV-2 variants and H1N1 infection. The methods employed included an ELISA-based trimeric spike protein binding assay, viral infection assays, plaque assays, and molecular docking studies. Results showed that 3-CQA blocked spike protein/angiotensin converting enzyme 2 (ACE2) binding for most SARS-CoV-2 variants of concern, except the Delta variant. Extracts from Green coffee bean and <i>E. purpurea</i> effectively blocked all variants tested. Additionally, antibodies blocked spike protein binding up to Omicron BA.2. Molecular docking suggested that 3-CQA binding to Omicron BA.1, BA.2, and BA.4, though not to the Delta spike protein, may lead to steric hindrance, preventing receptor-binding domain interactions with ACE2. Finally, both 3-CQA and <i>E. purpurea</i> extract showed preventive effects against H1N1 viral infection, though with lower potency compared to SARS-CoV-2. In conclusion, 3-CQA has potential as a phytoconstituent marker for herbs with bioactive properties against SARS-CoV-2 and H1N1 viral infections.