Possible involvement of neuropeptide Y sub-receptor 1 (NPY-Y1) in the anti-viral response of SARS-CoV-2 infection in Syrian hamster.

Co-administration of Molnupiravir and Remdesivir, treatments for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), inhibits viral replication and infectivity. Previous studies indicate that the neuropeptide Y sub-receptor 1 (NPY-Y1) is involved in influenza virus aggravation in mouse pulmonary phagocytes, but the exact mechanisms remain unclear. Understanding the NPY-Y1 receptor's involvement in influenza and SARS-CoV-2 in both mice and hamsters may help explore its potential as an indicator of viral infections and support the development of preventive care. This study examined the effects of Molnupiravir and Remdesivir on infected Syrian hamsters and the NPY pathway during SARS-CoV-2 infection. SARS-CoV-2 infection increased mRNA expression of NPY, NPY-Y1 receptors, and inflammatory cytokines and chemokines in hamster lungs. Co-administration of the drugs significantly reduced these expressions. Changes in NPY-Y1 receptor expression were correlated with NPY, IL-10, IL-12, and IFN-γ, implying a role in the antiviral response pathway. These findings highlight that changes in the mRNA expression levels of NPY and NPY-Y1 receptor are influenced by SARS-CoV-2 infection and that the antiviral drugs impact the NPY-NPY-Y1 receptor cascade. This implies the pathway's involvement in inflammatory responses during viral infection and its potential as a therapeutic target.