Grabiński Wojciech, Karachitos Andonis, Kicińska Anna
Department of Bioenergetics, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, 61-614 Poznań, Poland.
Int J Mol Sci. 2024 Nov 25;25(23):12661. doi: 10.3390/ijms252312661.
The extremely rapid development of understanding and technology that led to the containment of the COVID-19 pandemic resulted from collaborative efforts in the fields of (SARS-CoV-2) biology, pharmacology, vaccinology, and medicine. Perhaps surprisingly, much of the research was conducted using simple and efficient yeast models. In this manuscript, we describe how yeast, eukaryotic microorganisms, have been used to research this global challenge, focusing on the therapeutic potential of the studies discussed herein. Thus, we outline the role of yeast in studying viral protein interactions with the host cell proteome, including the binding of the SARS-CoV-2 virus spike protein to the human ACE2 receptor and its modulation. The production and exploration of viral antigens in yeast systems, which led to the development of two approved COVID-19 vaccines, are also detailed. Moreover, yeast platforms facilitating the discovery and production of single-domain antibodies (nanobodies) against SARS-CoV-2 are described. Methods guiding modern and efficient drug discovery are explained at length. In particular, we focus on studies designed to search for inhibitors of the main protease (Mpro), a unique target for anti-coronaviral therapies. We highlight the adaptability of the techniques used, providing opportunities for rapid modification and implementation alongside the evolution of the SARS-CoV-2 virus. Approaches introduced in yeast systems that may have universal potential application in studies of emerging viral diseases are also described.
对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）生物学、药理学、疫苗学和医学领域的协同努力，带来了对新冠疫情的认识和技术的飞速发展，从而实现了对该疫情的控制。或许令人惊讶的是，许多研究是使用简单高效的酵母模型进行的。在本手稿中，我们描述了真核微生物酵母如何被用于研究这一全球挑战，重点关注本文所讨论研究的治疗潜力。因此，我们概述了酵母在研究病毒蛋白与宿主细胞蛋白质组相互作用中的作用，包括SARS-CoV-2病毒刺突蛋白与人血管紧张素转换酶2（ACE2）受体的结合及其调节。还详细介绍了酵母系统中病毒抗原的生产和探索，这促成了两种获批的新冠疫苗的研发。此外，还描述了有助于发现和生产抗SARS-CoV-2单域抗体（纳米抗体）的酵母平台。详细解释了指导现代高效药物发现的方法。特别是，我们重点关注旨在寻找主要蛋白酶（Mpro）抑制剂的研究，Mpro是抗冠状病毒疗法的独特靶点。我们强调了所用技术的适应性，为随着SARS-CoV-2病毒的演变进行快速修改和应用提供了机会。还介绍了酵母系统中引入的方法，这些方法可能在新兴病毒性疾病研究中具有普遍的潜在应用价值。
