B-cell lymphoma-2 family proteins-activated proteases as potential therapeutic targets for influenza A virus and severe acute respiratory syndrome coronavirus-2: Killing two birds with one stone?

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to a global health emergency. There are many similarities between SARS-CoV-2 and influenza A virus (IAV); both are single-stranded RNA viruses infecting airway epithelial cells and have similar modes of replication and transmission. Like IAVs, SARS-CoV-2 infections poses serious challenges due to the lack of effective therapeutic interventions, frequent appearances of new strains of the virus, and development of drug resistance. New approaches to control these infectious agents may stem from cellular factors or pathways that directly or indirectly interact with viral proteins to enhance or inhibit virus replication. One of the emerging concepts is that host cellular factors and pathways are required for maintaining viral genome integrity, which is essential for viral replication. Although IAVs have been studied for several years and many cellular proteins involved in their replication and pathogenesis have been identified, very little is known about how SARS-CoV-2 hijacks host cellular proteins to promote their replication. IAV induces apoptotic cell death, mediated by the B-cell lymphoma-2 (Bcl-2) family proteins in infected epithelia, and the pro-apoptotic members of this family promotes viral replication by activating host cell proteases. This review compares the life cycle and mode of replication of IAV and SARS-CoV-2 and examines the potential roles of host cellular proteins, belonging to the Bcl-2 family, in SARS-CoV-2 replication to provide future research directions.