Replication organelles of hepatitis C virus and SARS-CoV-2: Surprising similarities and avenues for broad-spectrum antivirals

Positive single -strand RNA (+RNA) viruses can remodel host cell membranes to induce replication organelles isolating the replication of their genome from cellular innate immunity mechanisms. Some of these viruses, including the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), induce double-membrane vesicles (DMV) to behave as replication organelles. As for the hepatitis C virus (HCV), pores crossing both membranes of SARS-CoV-2-induced DMV have been identified. These pores likely allow the supply of metabolites essential for viral replication within the DMV, and allow the export of the newly synthesized viral RNA to form the genome of the neo-synthesized virions. However, it remains unknown whether DMV with open pores can coexist with fully sealed DMV allowing the storage of large amounts of viral RNA, as seen for the HCV model. Interestingly, recent studies have revealed many similarities in the mechanisms of DMV biogenesis between these two phylogenetically distant viruses. Understanding the mechanisms of DMV formation and function will be essential for the development of new broad-spectrum antiviral approaches, able to inhibit DMV-inducing viruses from different families. (c) 2023 l'Academie nationale de medecine. Published by Elsevier Masson SAS. All rights reserved.