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.
BloomDECadaretteD. Infectious disease threats in the twenty-first century: strengthening the global response. Front Immunol2019; 10: 549.
2.
NaghaviMMestrovicTGrayA, et al.Global burden associated with 85 pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Infect Dis2024; 24: 868–895.
3.
BakerREMahmudASMillerIF, et al.Infectious disease in an era of global change. Nat Rev Microbiol2022; 20: 193–205.
4.
UNAIDS. Global HIV & AIDS statistics — Fact sheet. 2024.
5.
World Health Organization (WHO). HIV data and statistics. 2025.
6.
World Health Organization (WHO). WHO Coronavirus (COVID-19) Dashboard. 2025.
7.
LiuQLiuMLiangW, et al.Global distribution and health impact of infectious disease outbreaks, 1996–2023: a worldwide retrospective analysis of World Health Organization emergency event reports. J Glob Health2025; 15: 04151.
8.
TulchinskyTHVaravikovaEA. Communicable diseases. New Public Health2014: 149–236. DOI: 10.1016/B978-0-12-415766-8.00004-5.
9.
Van SeventerJMHochbergNS. Principles of infectious diseases: transmission, diagnosis, prevention, and control. Int Encycl Public Health2016: 6: 22–39.
10.
SmithH. Biochemical challenge of microbial pathogenicity. Bacteriol Rev1968; 32: 164–184.
11.
VerhoefJvan KesselKSnippeH. Immune response in human pathology: infections caused by bacteria, viruses, fungi, and parasites. In: Nijkamp and Parnham's principles of immunopharmacology. Cham: Springer International Publishing, 2019, pp.165–178.
12.
ChenLDengHCuiH, et al.Inflammatory responses and inflammation-associated diseases in organs. Oncotarget2017; 9: 7204–7218.
13.
BarberMFFitzgeraldJR. Mechanisms of host adaptation by bacterial pathogens. FEMS Microbiol Rev2024; 48: fuae019.
14.
BerrySBHaackAJThebergeAB, et al.Host and pathogen communication in the respiratory tract: mechanisms and models of a complex signaling microenvironment. Front Med (Lausanne)2020; 7: 537.
DeroostKPhamTTOpdenakkerG,et al.The immunological balance between host and parasite in malaria. FEMS Microbiol Rev2016; 40: 208–257.
17.
SoniJSinhaSPandeyR. Understanding bacterial pathogenicity: a closer look at the journey of harmful microbes. Front Microbiol2024; 15: 1370818.
18.
KnodlerLACelliJ. Eating the strangers within: host control of intracellular bacteria via xenophagy. Cell Microbiol2011; 13: 1319–1327.
19.
GruenbergJVan der GootFG. Mechanisms of pathogen entry through the endosomal compartments. Nat Rev Mol Cell Biol2006; 7: 495–504.
20.
SenRNayakLDeRK. A review on host–pathogen interactions: classification and prediction. Eur J Clin Microbiol Infect Dis2016; 35: 1581–1599.
21.
BlancoLP. Initial host-pathogen interactions explained by the Organism Prearranged Recognition Theory: fundamental role of saccharides. Life Res2024; 7: 13.
22.
MaginnisMS. β-arrestins and G protein-coupled receptor kinases in viral entry: a graphical review. Cell Signal2023; 102: 110558.
23.
HattoriYMichelMC. G protein-coupled receptor kinases (GRKS) and β-arrestins: new insights into disease regulators. Front Pharmacol2020; 10: 1654.
24.
VerdecchiaPAngeliFReboldiG. Angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and coronavirus. J Hypertens2020; 38: 1190–1191.
25.
SharmaDSharmaJSinghA. Exploring the mystery of angiotensin-converting enzyme II (ACE2) in the battle against SARS-CoV-2. J Renin Angiotensin Aldosterone Syst2021; 2021: 9939929.
26.
SriramKMoyungKCorridenR, et al.GPCRs show widespread differential mRNA expression and frequent mutation and copy number variation in solid tumors. PLoS Biol2019; 17: e3000434.
27.
TipnisSRHooperNMHydeR, et al.A human homolog of angiotensin-converting enzyme: cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem2000; 275: 33238–33243.
28.
ChenLLiXChenM, et al.The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2. Cardiovasc Res2020; 116: 1097–1100.
29.
MarčetićDSamaržijaMVukić DugacA,et al.Angiotensin-converting enzyme 2 (Ace2) as a potential diagnostic and prognostic biomarker for chronic inflammatory lung diseases. Genes (Basel)2021; 12: 1054.
30.
AkbariAHadizadehAIslampanahM, et al.COVID-19, G protein-coupled receptor, and renin-angiotensin system autoantibodies: systematic review and meta-analysis. Autoimmun Rev2023; 22: 103402.
BourgonjeARAbdulleAETimensW, et al.Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19). J Pathol2020; 251: 228–248.
33.
HengBCAubelDFusseneggerM. An overview of the diverse roles of G-protein coupled receptors (GPCRs) in the pathophysiology of various human diseases. Biotechnol Adv2013; 31: 1676–1694.
34.
KunvariyaADDaveSAModiZJ, et al.Exploration of multifaceted molecular mechanism of angiotensin-converting enzyme 2 (ACE2) in pathogenesis of various diseases. Heliyon2023; 9: e15644.
35.
SansoèGAragnoM. New viral diseases and new possible remedies by means of the pharmacology of the renin-angiotensin system. J Renin Angiotensin Aldosterone Syst2023; 2023: 3362391.
36.
WagenaarGTMollGN. Clinical significance of intervention in the renin-angiotensin-aldosterone-apelinergic system. Eur J Pharmacol2025; 1003: 177866.
37.
Laragh JH and Sealey JE. Renin-angiotensin-aldosterone system and the renal regulation of sodium, potassium and blood pressure homeostasis. In: Windhager EE (ed.) Handbook of physiology. Vol II. New York: Oxford University Press for American Physiological Society, 1992.
38.
Szczepanska-SadowskaECzarzastaKCudnoch-JedrzejewskaA. Dysregulation of the renin-angiotensin system and the vasopressinergic system interactions in cardiovascular disorders. Curr Hypertens Rep2018; 20: 19.
39.
ValentiniAHeilmannRMKühneA, et al.The Renin–Angiotensin–Aldosterone System (RAAS): beyond cardiovascular regulation. Vet Sci2025; 12: 777.
40.
KarimiFMalekiMMovahedpourA, et al.Overview of the renin-angiotensin system in diabetic nephropathy. J Renin Angiotensin Aldosterone Syst2024; 25: 14703203241302966.
41.
BaderMSteckelingsUMAleninaN, et al.Alternative renin-angiotensin system. Hypertension2024; 81: 964–976.
42.
Rodríguez-PallaresJGarcia-CrivaroLAPargaJA,et al.Renin-angiotensin system as an emerging target to modulate adult neurogenesis in health and disease. Stem Cell Res Ther2025; 16: 332.
43.
RiceGIThomasDAGrantPJ, et al.Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism. Biochem J2004; 383: 45–51.
44.
TurnerAJHooperNM. The angiotensin–converting enzyme gene family: genomics and pharmacology. Trends Pharmacol Sci2002; 23: 177–183.
45.
Rodrigues-FerreiraSNahmiasC. G-protein coupled receptors of the renin-angiotensin system: new targets against breast cancer?Front Pharmacol2015; 6: 24.
46.
LiYLiBChenWD,et al.Role of G-protein coupled receptors in cardiovascular diseases. Front Cardiovasc Med2023; 10: 1130312.
47.
LinSPanHWuH, et al.Role of the ACE2-Ang-(1-7)-Mas axis in blood pressure regulation and its potential as an antihypertensive in functional foods. Mol Med Rep2017; 16: 4403–4412.
48.
ColinMDelaitreCFoulquierS,et al.The AT1/AT2 receptor equilibrium is a cornerstone of the regulation of the renin angiotensin system beyond the cardiovascular system. Molecules2023; 28: 5481.
49.
ErdösEG. Angiotensin I converting enzyme. Circ Res1975; 36: 247–255.
50.
VargasRAMillánJMBonillaEF. Renin–angiotensin system: basic and clinical aspects—a general perspective. Endocrinol Diabetes Nutr (Engl Ed)2022; 69: 52–62.
51.
Passos-SilvaDGVerano-BragaTSantosRA. Angiotensin-(1–7): beyond the cardio-renal actions. Clin Sci2013; 124: 443–456.
52.
TsutsumiNKildedalDFHansenOK, et al.Insight into structural properties of viral G protein-coupled receptors and their role in the viral infection: IUPHAR review 41. Br J Pharmacol2025; 182: 26–51.
CivciristovSHallsML. Signalling in response to sub-picomolar concentrations of active compounds: pushing the boundaries of GPCR sensitivity. Br J Pharmacol2019; 176: 2382–2401.
55.
AgbadaolaMTHilgerDKellerS,et al.Unraveling allosteric signaling of G protein-coupled receptors (GPCRs) by single-molecule fluorescence. Biophys Rev2025: 1–24. DOI: 10.1007/s12551-025-01361-3.
56.
NazFArishM. GPCRs as an emerging host-directed therapeutic target against mycobacterial infection: from notion to reality. Br J Pharmacol2022; 179: 4899–4909.
57.
MelvinJASchellerEVMillerJF,et al.Bordetella pertussis pathogenesis: current and future challenges. Nat Rev Microbiol2014; 12: 274–288.
58.
HolmgrenJ. Actions of cholera toxin and the prevention and treatment of cholera. Nature1981; 292: 413–417.
59.
GrandeFOcchiuzziMARizzutiB, et al.CCR5/CXCR4 Dual antagonism for the improvement of HIV infection therapy. Molecules2019; 24: 550.
60.
ZhangZZhangHZhengL, et al.CXCR4 Mediated recognition of HIV envelope spike and inhibition by CXCL12. Nat Commun2025; 16: 8653.
61.
MayberryCLSoucyANLajoieCR, et al.JC Polyomavirus entry by clathrin-mediated endocytosis is driven by β-arrestin. J Virol2019; 93: 10–128.
62.
BartheMHertereauLLamghariN, et al.Receptors and cofactors that contribute to SARS-CoV-2 entry: can skin be an alternative route of entry?Int J Mol Sci2023; 24: 6253.
63.
Roberts CA and Buikstra JE. Bacterial infections. In: Buikstra JE (ed.) Ortner's identification of pathological conditions in human skeletal remains. 3rd. London, England: Academic Press, 2019, pp. 321–439.
64.
LambeyPOtunOCongX, et al.Structural insights into recognition of chemokine receptors by Staphylococcus aureus leukotoxins. Elife2022; 11: e72555.
65.
Reyes-RoblesTAlonzoFKozhayaL, et al.Staphylococcus aureus leukotoxin ED targets the chemokine receptors CXCR1 and CXCR2 to kill leukocytes and promote infection. Cell Host Microbe2013; 14: 453–459.
66.
MarulloSScottMGEnslenH,et al.Mechanical activation of the β2-adrenergic receptor by meningococcus: a historical and future perspective analysis of how a bacterial probe can reveal signalling pathways in endothelial cells, and a unique mode of receptor activation involving its N-terminal glycan chains. Front Endocrinol (Lausanne)2022; 13: 883568.
Theel ES and Pritt BS. Parasites. In: Hayden RT, Wolk DM, Carroll KC, et al (eds) Diagnostic microbiology of the immunocompromised host. Washington, DC: Wiley, 2016, pp.411–466.
69.
ÓlafssonEBBarraganA. The unicellular eukaryotic parasite Toxoplasma gondii hijacks the migration machinery of mononuclear phagocytes to promote its dissemination. Biol Cell2020; 112: 239–250.
70.
WangPPJiangXZhuL, et al.A G-protein-coupled receptor modulates gametogenesis via PKG-mediated signaling cascade in Plasmodium berghei. Microbiol Spectr2022; 10: e00150-22.
71.
HarrisonTSamuelBUAkompongT, et al.Erythrocyte G protein-coupled receptor signaling in malarial infection. Science2003; 301: 1734–1736.
72.
VelagapudiRHsuehYPGeunes-BoyerS, et al.Spores as infectious propagules of Cryptococcus neoformans. Infect Immun2009; 77: 4345–4355.
73.
ChangYCMillerGFKwon-ChungKJ. Importance of a developmentally regulated pheromone receptor of Cryptococcus neoformans for virulence. Infect Immun2003; 71: 4953–4960.
74.
BallouERAvelarGMChildersDS, et al.Lactate signalling regulates fungal β-glucan masking and immune evasion. Nat Microbiol2016; 2: 1–9.
75.
CrabtreeJNOkagakiLHWiesnerDL, et al.Titan cell production enhances the virulence of Cryptococcus neoformans. Infect Immun2012; 80: 3776–3785.
76.
OkagakiLHWangYBallouER, et al.Cryptococcal titan cell formation is regulated by G-protein signaling in response to multiple stimuli. Eukaryot Cell2011; 10: 1306–1316.
77.
Duah-QuashieNOOpoku-AgyemanPLanzaM,et al.Polymorphisms in the human angiotensin converting enzyme gene (ACE) linked to susceptibility of COVID-19 and malaria infections in the Ghanaian population. Infect Genet Evol2024; 119: 105568.
78.
SubramaniamSRufWBosmannM. Advocacy of targeting protease-activated receptors in severe coronavirus disease 2019. Br J Pharmacol2022; 179: 2086–2099.
79.
OgunladeBOLazartiguesEFilipeanuCM. Angiotensin type 1 receptor-dependent internalization of SARS-CoV-2 by angiotensin-converting enzyme 2. Hypertension2021; 77: e42–e43.
80.
HerringtonCSCoatesPJDuprexWP. Viruses and disease: emerging concepts for prevention, diagnosis and treatment. J Pathol2015; 235: 149–152.
81.
AlcamiALiraSA. Modulation of chemokine activity by viruses. Curr Opin Immunol2010; 22: 482–487.
82.
LalaniASMcFaddenG. Evasion and exploitation of chemokines by viruses. Cytokine Growth Factor Rev1999; 10: 219–233.
83.
ZhangJFengHXuS,et al.Hijacking GPCRs by viral pathogens and tumor. Biochem Pharmacol2016; 114: 69–81.
84.
AlcamiA. Viral mimicry of cytokines, chemokines and their receptors. Nat Rev Immunol2003; 3: 36–50.
85.
PontejoSMMurphyPMPeaseJE. Chemokine subversion by human herpesviruses. J Innate Immun2018; 10: 465–478.
86.
McGeochDJMossHWMcNabDA,et al.DNA Sequence and genetic content of the Hin dIII l region in the short unique component of the herpes simplex virus type 2 genome: identification of the gene encoding glycoprotein G, and evolutionary comparisons. J Gen Virol1987; 68: 19–38.
87.
SuHKEberleRCourtneyRJ. Processing of the herpes simplex virus type 2 glycoprotein gG-2 results in secretion of a 34,000-Mr cleavage product. J Virol1987; 61: 1735–1737.
88.
JochumSMoosmannALangS, et al.The EBV immunoevasins vIL-10 and BNLF2a protect newly infected B cells from immune recognition and elimination. PLoS Pathog2012; 8: e1002704.
89.
LüttichauHR. The cytomegalovirus UL146 gene product vCXCL1 targets both CXCR1 and CXCR2 as an agonist. J Biol Chem2010; 285: 9137–9146.
90.
NgATscharkeDCReadingPC,et al.The vaccinia virus A41L protein is a soluble 30kDa glycoprotein that affects virus virulence. J Gen Virol2001; 82: 2095–2105.
91.
SmithCASmithTDSmolakPJ, et al.Poxvirus genomes encode a secreted, soluble protein that preferentially inhibits β chemokine activity yet lacks sequence homology to known chemokine receptors. Virology1997; 236: 316–327.
92.
ErazoAYeeMBOsterriederN,et al.Varicella-zoster virus open reading frame 66 protein kinase is required for efficient viral growth in primary human corneal stromal fibroblast cells. J Virol2008; 82: 7653–7665.
93.
ElphickGFQuerbesWJordanJA, et al.The human polyomavirus, JCV, uses serotonin receptors to infect cells. Science2004; 306: 1380–1383.
94.
Cabral-MarquesOHalpertGSchimkeLF, et al.Autoantibodies targeting GPCRs and RAS-related molecules associate with COVID-19 severity. Nat Commun2022; 13: 1220.
95.
VasquezMTLubkinAReyes-RoblesT, et al.Identification of a domain critical for Staphylococcus aureus LukED receptor targeting and lysis of erythrocytes. J Biol Chem2020; 295: 17241–17250.
96.
GrisonCMLambeyPJeannotS, et al.Molecular insights into mechanisms of GPCR hijacking by Staphylococcus aureus. Proc Natl Acad Sci USA2021; 118: e2108856118.
97.
Franco-ParedesCChastainDBAllenL,et al.Overview of cutaneous mycobacterial infections. Curr Trop Med Rep2018; 5: 228–232.
98.
GuptaPPandeyADeepakD,et al.Tuberculosis and leprosy co-infection: points to remember. Lung India2025; 42: 551–554.
99.
DahlVNMølhaveMFløeA, et al.Global trends of pulmonary infections with nontuberculous mycobacteria: a systematic review. Int J Infect Dis2022; 125: 120–131.
100.
AlaridahNLutayNTenlandE, et al.Mycobacteria manipulate G-protein-coupled receptors to increase mucosal Rac1 expression in the lungs. J Innate Immun2017; 9: 318–329.
101.
HåkanssonGLutayNAnderssonM, et al.Epithelial G protein-coupled receptor kinases regulate the initial inflammatory response during mycobacterial infection. Immunobiology2013; 218: 984–994.
102.
SaukkonenJJBazydloBThomasM, et al.β-chemokines are induced by Mycobacterium tuberculosis and inhibit its growth. Infect Immun2002; 70: 1684–1693.
103.
ColosimoDAKohnJALuoPM, et al.Mapping interactions of microbial metabolites with human G-protein-coupled receptors. Cell Host Microbe2019; 26: 273–282.
104.
BhattaraiYWilliamsBBBattaglioliEJ, et al.Gut microbiota-produced tryptamine activates an epithelial G-protein-coupled receptor to increase colonic secretion. Cell Host Microbe2018; 23: 775–785.
105.
CohenLJKangHSChuJ, et al.Functional metagenomic discovery of bacterial effectors in the human microbiome and isolation of commendamide, a GPCR G2A/132 agonist. Proc Natl Acad Sci USA2015; 112: E4825–E4834.
106.
MagerLFBurkhardRPettN, et al.Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy. Science2020; 369: 1481–1489.
107.
BryzekDCiastonIDoboszE, et al.Triggering NETosis via protease-activated receptor (PAR)-2 signaling as a mechanism of hijacking neutrophils function for pathogen benefits. PLoS Pathog2019; 15: e1007773.
108.
CoureuilMLécuyerHScottMG, et al.Meningococcus hijacks a β2-adrenoceptor/β-arrestin pathway to cross brain microvasculature endothelium. Cell2010; 143: 1149–1160.
109.
Osei-OwusuPCharltonTMKimHK, et al.FPR1 Is the plague receptor on host immune cells. Nature2019; 574: 57–62.
110.
WangXMaruvadaRMorrisAJ, et al.Sphingosine 1-phosphate activation of EGFR as a novel target for meningitic Escherichia coli penetration of the blood-brain barrier. PLoS Pathog2016; 12: e1005926.
111.
LinPChengTMaS, et al.Bacillus bombysepticus α-toxin binding to G protein-coupled receptor kinase 2 regulates cAMP/PKA signaling pathway to induce host death. PLoS Pathog2016; 12: e1005527.
112.
PereiraPHGarciaCR. Evidence of G-protein-coupled receptors (GPCR) in the parasitic protozoa Plasmodium falciparum—sensing the host environment and coupling within its molecular signaling toolkit. Int J Mol Sci2021; 22: 12381.
113.
MillhollandMGMishraSDupontCD, et al.A host GPCR signaling network required for the cytolysis of infected cells facilitates release of apicomplexan parasites. Cell Host Microbe2013; 13: 15–28.
114.
MoraesMSBuduASinghMK, et al.Plasmodium falciparum GPCR-like receptor SR25 mediates extracellular K+ sensing coupled to Ca2+ signaling and stress survival. Sci Rep2017; 7: 9545.
115.
FrancoEManning-CelaRMezaI. Signal transduction in entamoeba histolytica induced by interaction with fibronectin: presence and activation of Phosphokinase A and its possible relation to invasiveness. Arch Med Res2002; 33: 389–397.
116.
SantosBMDiasBKNakabashiM,et al.The knockout for G protein-coupled receptor-like PfSR25 increases the susceptibility of malaria parasites to the antimalarials lumefantrine and piperaquine but not to medicine for malaria venture compounds. Front Microbiol2021; 12: 638869.
117.
KumarSJainTBanerjeeD. Fungal diseases and their treatment: a holistic approach. In: Pathogenicity and drug resistance of human pathogens: mechanisms and novel approaches. Singapore: Springer Singapore, 2020, pp.111–134.
118.
BrownNASchrevensSVan DijckP,et al.Fungal G-protein-coupled receptors: mediators of pathogenesis and targets for disease control. Nat Microbiol2018; 3: 402–414.
119.
GaoJXuXHuangK,et al.Fungal G-protein-coupled receptors: a promising mediator of the impact of extracellular signals on biosynthesis of Ochratoxin A. Front Microbiol2021; 12: 631392.
120.
GehrkeAHeinekampTJacobsenID,et al.Heptahelical receptors GprC and GprD of Aspergillus fumigatus are essential regulators of colony growth, hyphal morphogenesis, and virulence. Appl Environ Microbiol2010; 76: 3989–3998.
121.
AlspaughJAPerfectJRHeitmanJ. Signal transduction pathways regulating differentiation and pathogenicity of Cryptococcus neoformans. Fungal Genet Biol1998; 25: 1–14.
122.
KnowlesSLMeadMESilvaLP, et al.Gliotoxin, a known virulence factor in the major human pathogen Aspergillus fumigatus, is also biosynthesized by its nonpathogenic relative Aspergillus fischeri. MBio2020; 11: e03361–19.
123.
FilhoAPBranciniGTde CastroPA, et al.Aspergillus fumigatus G-protein coupled receptors GprM and GprJ are important for the regulation of the cell wall integrity pathway, secondary metabolite production, and virulence. Mbio2020; 11: 10–128.
124.
MelakuL. Angiotensin-converting enzyme 2 and its potential protective effect upon heart. Arch Med Health Sci.2018; 6: 238–246.
125.
GheblawiMWangKViveirosA, et al.Angiotensin-converting enzyme 2: SARS-CoV-2 receptor and regulator of the renin-angiotensin system: celebrating the 20th anniversary of the discovery of ACE2. Circ Res2020; 126: 1456–1474.
126.
AvdoninPPRybakovaEYTrufanovSK,et al.SARS-CoV-2 receptors and their involvement in cell infection. Biochem (Mosc) Suppl A: Membr Cell Biol2023; 17: 1–11.
HammingITimensWBulthuisML, et al.Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol2004; 203: 631–637.
129.
KubaKImaiYRaoS, et al.A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus–induced lung injury. Nat Med2005; 11: 875–879.
YangGTanZZhouL, et al.Effects of angiotensin II receptor blockers and ACE (angiotensin-converting enzyme) inhibitors on virus infection, inflammatory status, and clinical outcomes in patients with COVID-19 and hypertension: a single-center retrospective study. Hypertension2020; 76: 51–58.
132.
da Silva-SantosYPagniRLGamonTHM, et al.Angiotensin-converting enzyme inhibition and/or angiotensin receptor blockade modulate cytokine profiles and improve clinical outcomes in experimental COVID-19 infection. Int J Mol Sci2025; 26: 7663.
133.
CarinoAMoracaFFiorilloB, et al.Hijacking SARS-CoV-2/ACE2 receptor interaction by natural and semi-synthetic steroidal agents acting on functional pockets on the receptor binding domain. Front Chem2020; 8: 572885.
134.
CaohuyHEidelmanOChenT, et al.Common cardiac medications potently inhibit ACE2 binding to the SARS-CoV-2 spike, and block virus penetration and infectivity in human lung cells. Sci Rep2021; 11: 22195.
135.
ZhangPNiemelaELópez CerdáS, et al.Host-directed virus-mimicking particles interacting with the ACE2 receptor competitively block coronavirus SARS-CoV-2 entry. Nano Lett2024; 24: 4064–4071.
136.
Abdel HameidRCormet-BoyakaEKueblerWM, et al.SARS-CoV-2 may hijack GPCR signaling pathways to dysregulate lung ion and fluid transport. Am J Physiol Lung Cell Mol Physiol2021; 320: L430–L435.
137.
ZhangQFriedmanPA. Receptor-loaded virion endangers gpcr signaling: mechanistic exploration of sars-cov-2 infections and pharmacological implications. Int J Mol Sci2021; 22: 10963.
138.
BanuNPanikarSSLealLR,et al.Protective role of ACE2 and its downregulation in SARS-CoV-2 infection leading to Macrophage Activation Syndrome: therapeutic implications. Life Sci2020; 256: 117905.
139.
MaLWilleyJ. The interplay between inflammation and thrombosis in COVID-19: mechanisms, therapeutic strategies, and challenges. Thromb Update2022; 8: 100117.
140.
FarahaniMNiknamZAmirabadLM, et al.Molecular pathways involved in COVID-19 and potential pathway-based therapeutic targets. Biomed Pharmacother2022; 145: 112420.
141.
CattaneoFGuerraGParisiM, et al.Cell-surface receptors transactivation mediated by G-protein-coupled receptors. Int J Mol Sci2014; 15: 19700–19728.
142.
MichaudVDeodharMArwoodM, et al.ACE2 As a therapeutic target for COVID-19; its role in infectious processes and regulation by modulators of the RAAS system. J Clin Med2020; 9: 2096.
143.
HauserASSreenivasCMasuhoI, et al.Pharmacogenomics of GPCR drug targets. Cell2017; 172: 41–54.e19.
144.
HarmerDGilbertMBormanR,et al.Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS Lett2002; 532: 107–110.
ElshafeiAKhidrEGEl-HusseinyAA,et al.RAAS, ACE2 and COVID-19; a mechanistic review. Saudi J Biol Sci2021; 28: 6465–6470.
147.
FengFChenJZhaoJ, et al.Killing two birds with one stone by administration of soluble ACE2: a promising strategy to treat both cardiovascular diseases and SARS-CoV-2 infection. Viruses2021; 13: 2243.
148.
ButtYKurdowskaAAllenTC. Acute lung injury: a clinical and molecular review. Arch Pathol Lab Med2016; 140: 345–350.
149.
LingYWeiJWangA,et al.Advances in the pathogenesis of acute lung injury and acute respiratory distress syndrome. Teratog Carcinog Mutagen2017; 29: 151–154.
150.
SharmaRKLiJKrishnanS, et al.Angiotensin-converting enzyme 2 and COVID-19 in cardiorenal diseases. Clin Sci2021; 135: 1–17.
151.
MirzaMUSaadabadiAVanmeertM, et al.Discovery of HIV entry inhibitors via a hybrid CXCR4 and CCR5 receptor pharmacophore-based virtual screening approach. Eur J Pharm Sci2020; 155: 105537.
152.
ZhangNDuB. Reply to Rubinstein: is Lgr4 essential for VSV–and VSV-G–pseudotyped lentiviral vector entry to cells?J Biol Chem2018; 293: 113.
153.
RubinsteinM. Is Lgr4 essential for VSV–and VSV-G–pseudotyped lentiviral vector entry to cells?J Biol Chem2018; 293: 112.
