Hijacking of GPCRs and angiotensin-converting enzyme-2 in the pathophysiology of infectious diseases

Introduction Infectious diseases caused by pathogens have posed health concerns worldwide since ancient times, and the development of preventive approaches has been a focus. Pathogens establish infections by targeting particular host protein receptors, such as angiotensin-converting enzyme-2 (ACE2), membrane-anchored proteins, or signaling components like G-protein-coupled receptors (GPCRs), through interactions or by modulating host proteins via secreted toxic compounds. GPCRs are broadly distributed receptors regulating multiple physiological activities, from neurotransmitter feedback and environmental triggers to hormonal feedback. Innumerable pathogens target 100 of the GPCRs in different ways to evade immune responses, survival, and virulence. Method For the synthesis of this review, the literature was searched in databases by using the search engines (like PubMed, SCOPUS, Web of Sciences, ScienceDirect, Google Scholar, etc.), and the following keywords: “Infectious Diseases, G-protein coupled receptors (GPCRs), angiotensin converting enzyme-2 (ACE-2), Pathophysiology, Renin-angiotensin-aldosterone system (RAAS)” were used. Conclusions This focused review emphasizes the roles of GPCR and ACE2 receptors in the RAAS, pathophysiology of infectious diseases, and their impact on these receptor-mediated downstream signaling pathways. The current article also discussed the impact of GPCRs and ACE2 receptors on pathogenicity and host cellular responses, and on improving our knowledge of host-pathogen interactions at the molecular and cellular levels; therefore, it might open avenues for novel therapeutic agents and preventive approaches.