COVID-19 大流行提醒我们迫切需要新的抗病毒药物来控制新出现的传染病和未来潜在的大流行。免疫疗法彻底改变了肿瘤学，并可以补充抗病毒药物的使用，但其在传染病中的应用在很大程度上仍未得到探索。核苷类似物是一类广泛用作抗病毒和抗肿瘤药物的药物。它们的抗病毒活性通常基于干扰病毒核酸复制或转录。根据我们之前的工作和计算机模型，我们假设抗病毒腺苷类似物（如瑞德西韦）具有以前未被识别的免疫调节特性，这有助于其治疗活性。就瑞德西韦而言，我们在此表明​​这些特性归因于其代谢物 GS-441524，它充当腺苷 A2A 受体拮抗剂。我们的研究结果支持了设计具有双重免疫调节和内在抗病毒特性的下一代抗病毒药物的新原理。这些化合物可能代表改变游戏规则的疗法，以控制新出现的病毒性疾病和未来的流行病。© 2024。作者。

The COVID-19 pandemic reminded us of the urgent need for new antivirals to control emerging infectious diseases and potential future pandemics. Immunotherapy has revolutionized oncology and could complement the use of antivirals, but its application to infectious diseases remains largely unexplored. Nucleoside analogs are a class of agents widely used as antiviral and anti-neoplastic drugs. Their antiviral activity is generally based on interference with viral nucleic acid replication or transcription. Based on our previous work and computer modeling, we hypothesize that antiviral adenosine analogs, like remdesivir, have previously unrecognized immunomodulatory properties which contribute to their therapeutic activity. In the case of remdesivir, we here show that these properties are due to its metabolite, GS-441524, acting as an Adenosine A2A Receptor antagonist. Our findings support a new rationale for the design of next-generation antiviral agents with dual - immunomodulatory and intrinsic - antiviral properties. These compounds could represent game-changing therapies to control emerging viral diseases and future pandemics.© 2024. The Author(s).