Priming of SARS-CoV-2 S protein by several membrane-bound serine proteinases could explain enhanced viral infectivity and systemic COVID-19 infection
| Autor: | Fuentes-Prior, Pablo |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
structure–function relationship Disease Kidney medicine.disease_cause Membrane Fusion Biochemistry HAI-1/SPINT1 α2-AP α2-antiplasmin Coronavirus membrane-associated serine proteinases (MASPs) Infectivity Membrane Glycoproteins Serine Endopeptidases MASPs membrane-associated serine proteinases uPA urokinase-type plasminogen activator Isoenzymes Liver Host-Pathogen Interactions Spike Glycoprotein Coronavirus QM/MD quantum mechanical/molecular dynamics Receptors Virus Angiotensin-Converting Enzyme 2 Signal Transduction Viral protein coronaviruses Proteinase Inhibitory Proteins Secretory Reviews Biology Serpin ACE2 angiotensin-converting enzyme 2 03 medical and health sciences Viral entry medicine Humans SARS severe acute respiratory syndrome PAI-1 plasminogen activator inhibitor 1 spike (S) protein Pandemics Molecular Biology TMPRSS2 Tropism Serine protease cell tropism 030102 biochemistry & molecular biology SARS-CoV-2 Myocardium serpins MERS Middle East respiratory syndrome COVID-19 Cell Biology 030104 developmental biology Gene Expression Regulation Immunology biology.protein PCI protein C inhibitor viral fusion |
| Zdroj: | The Journal of Biological Chemistry Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.rev120.015980 |
| Popis: | The ongoing COVID-19 pandemic has already caused over a million deaths worldwide, and this death toll will be much higher before effective treatments and vaccines are available. The causative agent of the disease, the coronavirus SARS-CoV-2, shows important similarities with the previously emerged SARS-CoV-1, but also striking differences. First, SARS-CoV-2 possesses a significantly higher transmission rate and infectivity than SARS-CoV-1 and has infected in a few months over 60 million people. Moreover, COVID-19 has a systemic character, as in addition to the lungs, it also affects the heart, liver, and kidneys among other organs of the patients and causes frequent thrombotic and neurological complications. In fact, the term "viral sepsis" has been recently coined to describe the clinical observations. Here I review current structure-function information on the viral spike proteins and the membrane fusion process to provide plausible explanations for these observations. I hypothesize that several membrane-associated serine proteinases (MASPs), in synergy with or in place of TMPRSS2, contribute to activate the SARS-CoV-2 spike protein. Relative concentrations of the attachment receptor, ACE2, MASPs, their endogenous inhibitors (the Kunitz-type transmembrane inhibitors, HAI-1/SPINT1 and HAI-2/SPINT2, as well as major circulating serpins) would determine the infection rate of host cells. The exclusive or predominant expression of major MASPs in specific human organs suggests a direct role of these proteinases in e.g., heart infection and myocardial injury, liver dysfunction, kidney damage, as well as neurological complications. Thorough consideration of these factors could have a positive impact on the control of the current COVID-19 pandemic. |
| Databáze: | OpenAIRE |
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