Structural investigations of proteins encoded by SARS-CoV-2.

ABSTRACT

It is hard to overestimate the influence of the COVID-19 pandemic on scientific research in the last two and a half years. Within a few weeks after the first cases of the disease were reported, the causative agent, now known as SARS-CoV-2, was identified, its genome was sequenced, individual proteins were expressed and purified, and structural work commenced. The originally described SARS-CoV-2 isolate (GenBank MN908947.3) has a positive-sense single-stranded (ss) RNA genome consisting of 29,903 bases. The genome encodes 29 proteins falling into structural and nonstructural categories, expressed as polyproteins that have to be cleaved into the final products by two virally encoded cysteine proteases. This "In the Limelight" special issue of FEBS Open Bio includes three review articles, focused on different aspects of the structure and other properties of selected examples of SARS-CoV-2 proteins (a) the properties of the Nsp14 and Nsp15 ribonucleases; (b) the current state of knowledge of the molecular mechanisms for the translation of both viral transcripts and cellular messenger RNAs, with a focus on the properties of the Nsp1 protein; and (c) the structural properties and evolution of the spike proteins in SARS-CoV-2 and other coronaviruses. These three reviews describe very different aspects of work that ultimately should lead to the development of more vaccines, antibodies, and small molecule drugs, necessary to combat this pandemic, as well as to counter future variants of this coronavirus.