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Fig. 1 | Virology Journal

Fig. 1

From: Keep out! SARS-CoV-2 entry inhibitors: their role and utility as COVID-19 therapeutics

Fig. 1

Overview of SARS-CoV-2 life cycle and inhibitors of viral entry. SARS-CoV-2 first binds to ACE2 on the cell surface and then releases RNA into the cytosol from the endosome following endocytosis and cathepsin activation, or directly from the cell surface membrane following S activation by proteases such as furin and TMPRSS2. In the cytosol, the ( +) genomic RNA is directly translated from the ORF1a/b into polyproteins containing non-structural proteins of the complex replicase machinery (e.g. RdRp). (-) sense RNA is synthesized and becomes a template for ( +) sense genomic RNA and sub-genomic RNA from which structural proteins and accessory proteins are made. These proteins and the genomic RNA will be utilized to assemble new virions that will exit the cell via exocytosis. The virions and the death of infected cell will induce immune response from the host. At each stage of entry shown, a number of candidates (shown in red) that inhibit each of the highlighted viral entry checkpoints (including cellular receptors, enzymes and viral proteins) have demonstrated efficacy against infection, preclinically, clinically or both. (Figure created using Biorender.)

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