Figure 4.

Schematic representation of 3CLpro effects in viral replication and STAT1 degradation. SARS-CoV-2 is a positive-sense single-stranded RNA virus. Upon fusion of the viral and host cell membranes, viral genomic RNA is released in the cytoplasm. (A) the viral RNA initiates the translation of co-terminal polypeptides 1a and 1ab. These polyproteins are subsequently cleaved by 3CLpro protease into non-structural proteins such as RNA-dependent RNA polymerase, helicase and ribonucleases; (B) the coronavirus replicase-transcriptase complex is an assembly of viral and cellular proteins that mediates the synthesis of genome- and subgenome-sized mRNAs in the virus-infected cell; (C) in the course of the SARS-CoV-2 infective cycle, the replicase-transcriptase complex amplifies the genomic RNA and synthesizes mRNAs that encode the structural proteins of the virus and proteins that are non-essential for replication in cell culture but appear to confer a selective advantage in vivo (accessory proteins); (D) production of new virions. The autophagic process is divided into four distinct stages: (1) Initiation, (2) autophagosomal formation (elongation), (3) autophagosome-lysosome fusion, and (4) autophagolysosome formation and cargo degradation. LC3B is a central protein in the autophagy pathway, where it functions in autophagy substrate selection and autophagosome biogenesis. 3CLpro could promote the colocalization between STAT1 and LC3B causing the autophagic degradation of STAT1, as shown by the rescue of STAT1 by autophagy/autolysosome inhibitor 3-methyladenine and bafilomycin A1.