PDF(Pubmed)
Abstract：
The appearance of new respiratory virus infections in humans with epidemic or pandemic potential has underscored the urgent need for effective broad-spectrum antivirals (BSAs). Bioactive compounds derived from plants may provide a natural source of new BSA candidates. Here, we investigated the novel phytocomplex formulation SP4™ as a candidate direct-acting BSA against major current human respiratory viruses, including coronaviruses and influenza viruses. SP4™ inhibited the in vitro replication of SARS-CoV-2, hCoV-OC43, hCoV-229E, Influenza A and B viruses, and respiratory syncytial virus in the low-microgram range. Using hCoV-OC43 as a representative respiratory virus, most of the antiviral activity of SP4™ was observed to stem primarily from its dimeric A-type proanthocyanidin (PAC-A) component. Further investigations of the mechanistic mode of action showed SP4™ and its PAC-A-rich fraction to prevent hCoV-OC43 from attaching to target cells and exert virucidal activity. This occurred through their interaction with the spike protein of hCoV-OC43 and SARS-CoV-2, thereby interfering with spike functions and leading to the loss of virion infectivity. Overall, these findings support the further development of SP4™ as a candidate BSA of a natural origin for the prevention of human respiratory virus infections.
摘要：
在具有流行病或大流行潜力的人类中出现新的呼吸道病毒感染强调了对有效的广谱抗病毒药物(BSA)的迫切需要。源自植物的生物活性化合物可以提供新的BSA候选物的天然来源。这里,我们研究了新型植物复合物制剂SP4™作为针对当前主要人类呼吸道病毒的候选直接作用BSA，包括冠状病毒和流感病毒。SP4™抑制SARS-CoV-2，hCoV-OC43，hCoV-229E，甲型和乙型流感病毒，和低微克范围的呼吸道合胞病毒。使用hCoV-OC43作为代表性呼吸道病毒，观察到SP4™的大部分抗病毒活性主要源于其二聚体A型原花青素(PAC-A)组分。对作用机理模式的进一步研究显示SP4™及其富含PAC-A的部分防止hCoV-OC43附着于靶细胞并发挥杀病毒活性。这是通过它们与hCoV-OC43和SARS-CoV-2的刺突蛋白相互作用而发生的，从而干扰了刺突功能并导致病毒体感染性丧失。总的来说,这些发现支持SP4™作为天然来源的候选BSA用于预防人类呼吸道病毒感染的进一步发展。
