Dark Proteome of Newly Emerged SARS-CoV-2 in Comparison with Human and Bat Coronaviruses

Rajanish Giri; Taniya Bhardwaj; Meenakshi Shegane; Bhuvaneshwari R. Gehi; Prateek Kumar; Kundlik Gadhave

Proteins ORF3a and ORF3b. ORF3a is a multifunctional protein with the molecular weight of ~31 kDa that has been found to localize in different organelles inside the host cells. Also referred to as U274, X1, and ORF3, the gene for this protein is present between the S and E genes of the SARS-CoV genome [90] [91] [92] . The homo-tetrameric complex of ORF3a has been demonstrated to form a potassium-ion channel on the host cell plasma membrane [93] . It performs a major function during virion assembly by co-localizing with E, M, and S viral proteins [94, 95] . ORF3b protein can be found in the cytoplasm, nucleolus, and outer membrane of mitochondria of the host cells [96, 97] . In Huh 7 cells, its over-expression has been linked with the activation of AP-1 via ERK and JNK pathways [98] . Transfection of ORF3b-EGFP leads to cell growth arrest at the G0/G1 phase of Vero, 293, and COS-7 cells [99] . ORF3a induces apoptosis via caspase 8/9 directed mitochondrial-mediated pathways, while ORF3b is reported to affect only the caspase 3-related pathways [100, 101] .