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Review
. 2022:132:243-277.
doi: 10.1016/bs.apcsb.2022.05.010. Epub 2022 Jun 9.

Interaction between Sars-CoV-2 structural proteins and host cellular receptors: From basic mechanisms to clinical perspectives

Henry Wade  1 , Qihua Duan  1 , Qiaozhu Su  2
Affiliations
Review

Interaction between Sars-CoV-2 structural proteins and host cellular receptors: From basic mechanisms to clinical perspectives

Henry Wade et al. Adv Protein Chem Struct Biol. 2022.

Abstract

Severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2) has caused a global pandemic that has affected the lives of billions of individuals. Sars-CoV-2 primarily infects human cells by binding of the viral spike protein to angiotensin-converting enzyme 2 (ACE2). In addition, novel means of viral entry are currently being investigated, including Neuropillin 1, toll-like receptors (TLRs), cluster of differentiation 147 (CD147), and integrin α5β1. Enriched expression of these proteins across metabolic regulatory organs/tissues, including the circulatory system, liver, pancreas, and intestine contributes to major clinical complications among COVID-19 patients, particularly the development of hypertension, myocardial injury, arrhythmia, acute coronary syndrome and increased coagulation in the circulatory system during and post-infection. Pre-existing metabolic disease, such as cardiovascular disease, obesity, diabetes, and non-alcoholic fatty liver disease, is associated with increased risk of hospitalization, persistent post-infection complications and worse outcomes in patients with COVID-19. This review overviews the biological features of Sars-CoV-2, highlights recent findings that delineate the pathological mechanisms of COVID-19 and the consequent clinical diseases.

Keywords: ACE2; COVID-19; Cardiovascular disease; Cytokine storm; Diabetes; Hypertension; NAFLD; Sars-CoV-2.

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Figures

Fig. 1
Fig. 1
Sars-CoV-2 induces cardiovascular dysfunction via ACE2 and enhances NAFLD (1) Sars-CoV-2 enters the body via the ACE2 expressing epithelia of the eyes, lungs, and digestive system. (2) Sars-CoV-2 enters cells by binding between the viral S-protein and host-cell surface proteins ACE2, CD147, or NRP1. Digestion of the S-protein by Furin and/or TMPRSS2 is essential for viral internalization. The viral RNA genome is released to facilitate replication and translation of viral proteins that assemble as new viral particles. (3) Translation of viral proteins induces downregulation of antiviral IFN signaling, upregulation of ROS production, mitochondrial damage, and destabilization of calcium ion homeostasis. (4) Newly synthesized virions are released into circulation where the S-protein of Sars-CoV-2 competes with vasoconstrictors AngI and AngII for ACE2 causing accumulation of AngI and AngII and the consequently chronic vasoconstriction, leading to hypertension. (5) Sars-CoV-2 infects the contractile cardiomyocytes of the heart, inducing cardiomyopathy. (6) Sars-CoV-2 infects hepatocytes of the liver, enhancing inflammation and promoting fibrogenesis, particularly in NAFLD/NASH patients. (7) Newly synthesized virions further _target the eyes, lungs and the digestive system to amplify the pathological conditions.
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