Department of Chemistry, Materials and Chemical Engineering "G. Natta", Politecnico di Milano, Via Mancinelli 7, 20131 Milano, Italy.
Department of Scienze, University of Basilicata, Viale dell'Ateneo Lucano 10, 85100 Potenza, Italy.
Viruses. 2024 Feb 22;16(3):338. doi: 10.3390/v16030338.
The continuous emergence of SARS-CoV-2 variants caused the persistence of the COVID-19 epidemic and challenged the effectiveness of the existing vaccines. The viral proteases are the most attractive targets for developing antiviral drugs. In this scenario, our study explores the use of HIV-1 protease inhibitors against SARS-CoV-2. An in silico screening of a library of HIV-1 proteases identified four anti-HIV compounds able to interact with the 3CL of SARS-CoV-2. Thus, in vitro studies were designed to evaluate their potential antiviral effectiveness against SARS-CoV-2. We employed pseudovirus technology to simulate, in a highly safe manner, the adsorption of the alpha (α-SARS-CoV-2) and omicron (ο-SARS-CoV-2) variants of SARS-CoV-2 and study the inhibitory mechanism of the selected compounds for cell-virus interaction. The results reported a mild activity against the viral proteases 3CL and PL, but efficient inhibitory effects on the internalization of both variants mediated by cathepsin B/L. Our findings provide insights into the feasibility of using drugs exhibiting antiviral effects for other viruses against the viral and host SARS-CoV-2 proteases required for entry.
不断出现的 SARS-CoV-2 变体导致 COVID-19 疫情持续存在，并挑战了现有疫苗的有效性。病毒蛋白酶是开发抗病毒药物最具吸引力的靶标。在这种情况下，我们的研究探讨了使用 HIV-1 蛋白酶抑制剂来对抗 SARS-CoV-2。对 HIV-1 蛋白酶文库进行计算机筛选，确定了四种能够与 SARS-CoV-2 的 3CL 相互作用的抗 HIV 化合物。因此，设计了体外研究来评估它们对 SARS-CoV-2 的潜在抗病毒效果。我们采用假病毒技术，以高度安全的方式模拟 SARS-CoV-2 的 alpha（α-SARS-CoV-2）和 omicron（ο-SARS-CoV-2）变体的吸附，并研究所选化合物对细胞-病毒相互作用的抑制机制。结果表明，这些化合物对 3CL 和 PL 病毒蛋白酶表现出轻微的活性，但对 cathepsin B/L 介导的两种变体的内化具有有效的抑制作用。我们的研究结果为使用具有抗病毒作用的药物来对抗其他病毒的病毒和宿主 SARS-CoV-2 蛋白酶，从而进入细胞提供了可行性的见解。
