PMC:7200337 / 73069-75250 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7200337","sourcedb":"PMC","sourceid":"7200337","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7200337","text":"RdRp Inhibitors\nThe CoV RNA-dependent RNA polymerase (RdRp) catalyzes the synthesis of viral RNA (Gao et al., 2020a), making it essential for viral replication and a prime target for antiviral inhibitors. Remdesivir, an adenosine triphosphate analog, inhibits RdRp by binding to RNA strands and preventing additional nucleotides from being added, thereby terminating viral RNA transcription (Figure 6 A) (Agostini et al., 2018). Remdesivir has been previously shown to be effective against MERS-CoV and SARS-CoV-1 infections in animal models (Sheahan et al., 2017, de Wit et al., 2020). Similarly, a study investigated the efficacy of remdesivir treatments on 12 rhesus macaques with SARS-CoV-2 infections (Williamson et al., 2020). Macaques treated with remdesivir showed a reduction in lung viral loads and pneumonia symptoms but no reduction in virus shedding. This study does provide evidence that if administered early enough, remdesivir may be effective at treating SARS-CoV-2 infections.\nFigure 6 Available Therapeutic Options to Manage COVID-19 Immunopathology and to Deter Viral Propagation\n(A) Rdrp inhibitors (remdesivir, favipiravir), protease inhibitors (lopinavir/ritonavir), and antifusion inhibitors (arbidol) are currently being investigated in their efficacy in controlling SARS-CoV-2 infections.\n(B) CQ and HCQ increase the pH within lysosomes, impairing viral transit through the endolysosomal pathway. Reduced proteolytic function within lysosomes augments antigen processing for presentation on MHC complexes and increases CTLA4 expression on Tregs.\n(C) Antagonism of IL-6 signaling pathway and of other cytokine-/chemokine-associated targets has been proposed to control COVID-19 CRS. These include secreted factors like GM-CSF that contribute to the recruitment of inflammatory monocytes and macrophages.\n(D) Several potential sources of SARS-CoV-2 neutralizing antibodies are currently under investigation, including monoclonal antibodies, polyclonal antibodies, and convalescent plasma from recovered COVID-19 patients.\nGM-CSF, granulocyte-macrophage colony-stimulating factor; CQ, chloroquine; HCQ, hydroxychloroquine; RdRp, RNA-dependent RNA 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