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Fig. 3 | Virology Journal

Fig. 3

From: Precision therapeutic targets for COVID-19

Fig. 3

Key elements of SARS-CoV-2 viral replication and some therapeutic targets. (a) ( +) RNA viruses are ‘ribosome-ready’, meaning that upon cytoplasmic entry, their genome is recognized by the host ribosome as mRNA and can immediately be translated. During translation, the viral genome employs a technique called 'ribosomal frameshifting' to produce two types of polyproteins, pp1a and pp1ab, which encode the non-structural proteins (nsps) including the viral protease MPro/nsp5 [232]. MPro first autocleaves  the polyproteins at a Gln/Ala and Gln/Ser junction, then cleaves most of the remaining proteins from the first two reading frames of the viral genome, including RdRp [232]. RdRp integrates with nsp7 and nsp8 to assemble into the polymerase holoenzyme. (b) The 3′ region of SARS-CoV-2 RNA genome encodes its structural proteins, S, Envelope (E), Membrane (M) and Nucleocapsid (N) proteins. Discontinuous transcription of the 3′ region generates a nested set of subgenomic ( −) RNAs that are copied into ( +) mRNA, resulting in the host ribosomal translation of the structural proteins [196]. RdRp is also responsible for replicating the viral genome for packaging. Replication and transcription processes are localized into interconnected, double-membraned, ER-derived vesicles called replicase-transcriptase complex (RTC) [189, 244], which centralize the machinery required for these processes and serve as a buffer to any host immune response [245]. Viral structural proteins are translated by host ribosomes from the subgenomic RNA synthesized by RdRp. After processing in the ER-Golgi Intermediate Compartment (ERGIC), the structural proteins and viral RNA are transported to budding vesicles. Finally, virus particles are assembled and released by exocytosis. PDB codes for structures are referenced in Additional file 1: Table 5. Figure was created with BioRender.com

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