Viruses rely on the host cell machinery to enter host cells and to initiate the infection. GPCR-mediated cell signaling pathways regulate the cellular and physiological processes. Most importantly, Beta-arrestins and GPCR signaling effectors (GRKs) are responsible for viral entry and replication in to the host cells. Several viruses encompassing flaviviruses, influenza, and polioviruses and SARS Cov-2 activate or require GPCR signaling pathways for viral entry which makes them potential targets for anti-viral therapies . A recent study focuses on the role of ACE2 receptor in the viral entry and progression of SARS Cov-2.