Interferon lambda (IFN-λ) is an antiviral naturally produced in response to viral infections, with activity on cells of epithelial origin and located in the mucosal surfaces. This localized activity results in reduced toxicity compared to type I IFNs, whose receptors are ubiquitously expressed. IFN-λ has been effective in the therapy of respiratory viral infections, playing a crucial role in potentiating adaptive immune responses that initiate at mucosal surfaces. Human IFN-λ has polymorphisms that may cause differences in the interaction with the specific receptor in the human population. Interestingly, bovine IFN-λ3 has an in silico-predicted higher affinity for the human receptor than its human counterparts, with high identity with different human IFN-λ variants, making it a suitable antiviral therapeutic candidate for human health. Here, we demonstrate that a recombinant bovine IFN-λ (rbIFN-λ) produced in HEK-293 cells is effective in preventing SARS-CoV-2 infection of VERO cells, with an inhibitory concentration 50% (IC50) between 30 and 50 times lower than that of human type I IFN tested here (α2b and β1a). We also demonstrated the absence of toxicity of rbIFN-λ in human PBMCs and the lack of proinflammatory activity on these cells. Altogether, our results show that rbIFN-λ is as an effective antiviral potentially suitable for COVID-19 therapy. Among other potential applications, rbIFN-λ could be useful to preclude virus dispersion to the lungs and/or to reduce transmission from infected people. Moreover, and due to the non-specific activity of this IFN, it can be potentially effective against other respiratory viruses that may be circulating together with SARS-CoV-2.

λ 干扰素 (IFN-λ) 是一种针对病毒感染而自然产生的抗病毒药物，对位于粘膜表面的上皮来源细胞具有活性。与I型干扰素相比，这种局部活性导致毒性降低，I型干扰素的受体普遍表达。IFN-λ 可有效治疗呼吸道病毒感染，在增强粘膜表面启动的适应性免疫反应方面发挥着至关重要的作用。人类 IFN-λ 具有多态性，可能会导致与人群中特定受体的相互作用存在差异。有趣的是，牛 IFN-λ3 具有计算机模拟-预测该人类受体的亲和力高于人类受体，与不同的人类 IFN-λ 变体具有高度同一性，使其成为适合人类健康的抗病毒治疗候选药物。在此，我们证明在 HEK-293 细胞中产生的重组牛 IFN-λ (rbIFN-λ) 可有效预防 VERO 细胞的 SARS-CoV-2 感染，抑制浓度 50% (IC50) 为 30 至 50 倍低于此处测试的人类 I 型干扰素（α2b 和 β1a）。我们还证明了 rbIFN-λ 在人 PBMC 中不存在毒性，并且对这些细胞缺乏促炎活性。总而言之，我们的结果表明 rbIFN-λ 是一种有效的抗病毒药物，可能适合 COVID-19 治疗。在其他潜在应用中，rbIFN-λ 可用于阻止病毒扩散到肺部和/或减少感染者的传播。此外，由于这种 IFN 的非特异性活性，它可能对可能与 SARS-CoV-2 一起传播的其他呼吸道病毒有效。