Mass spectrometry-based proteomics in basic and translational research of SARS-CoV-2 coronavirus and its emerging mutants

摘要

Genome and proteome organization of SARS-CoV-2. Positive-sense single-stranded RNA genome of SARS-CoV-2 (29,903 nucleotides) is composed of two non-structural open reading frames (replicase polyprotein 1a, R1A_SARS2, and replicase polyprotein 1ab, R1AB_SARS2), four structural (spike glycoprotein, SPIKE_SARS2; envelope small membrane protein, VEMP_SARS2; membrane protein, VME1_SARS2; and nucleoprotein, NCAP_SARS2), six accessory non-overlapping open reading frames (ORF3a protein, AP3A_SARS2; ORF6 protein, NS6_SARS2; ORF7a protein, NS7A_SARS2; ORF7b protein, NS7B_SARS2; ORF8 protein, NS8_SARS2; and ORF10 protein, A0A663DJA2_SARS2), and five accessory overlapping open reading frames (ORF3b protein, ORF3B_SARS2; ORF3c protein, ORF3C_SARS2; ORF3d protein, ORF3D_SARS2; ORF9b protein, ORF9B_SARS2; and ORF9c protein, ORF9C_SARS2). Due to a ribosomal frameshift, ORF1ab gene is translated into two replicase polyproteins. Viral proteases PLpro1/PLpro2 (non-structural protein 3; nsp3) and 3CLpro (3C-like proteinase; nsp5) are auto-cleaved from polyproteins and complete the cleavage of the remaining 14 non-structural proteins