SARS-CoV-2 Genome and S2 Spike Protein: IRF-Driven Interferon Regulation and Host Cell Responses

Coronaviruses, members of the betacoronavirus genus. They are mostly enveloped and has +ve sense RNA which infects a wide range of hosts, including mammals and birds. This SARS-CoV-2 in December 2019 triggered a global pandemic, with transmission primarily occurring through respiratory droplets. SARS-CoV-2 comprises four structural proteins namely: spike, membrane, envelope and nucleocapsid protein (S, M, E, and N respectively) along with multiple non-structural proteins (nsp1-nsp16) essential for infections. The trimeric S protein, composed of S1 and S2 subunits which helps in virus entry into the cell after attachment to the ACE2 recpetor of host cell. Interferon regulatory factors (IRF-1 and IRF-2) are critical transcription factors in antiviral immune responses, yet their specific roles in SARS-CoV-2 infection remain insufficiently understood. Disruption of their regulatory functions may compromise host antiviral defenses and influence disease progression. Elucidating the mechanistic roles of IRF-1 and IRF-2 could facilitate the production of novel therapeutic strategies which further modulates the immune responses, mitigates the viral pathogenicity, and hence clinical outcomes will be improved. A deep insight of these immune pathways is pivotal for designing targeted interventions to strengthen host resilience against coronavirus infections.