Insights to SARS-CoV-2 life cycle, pathophysiology, and rationalized treatments that target COVID-19 clinical complications

Background Gaining further insights into SARS-CoV-2 routes of infection and the underlying pathobiology of COVID-19 will support the design of rational treatments targeting the life cycle of the virus and/or the adverse effects (e.g., multi-organ collapse) that are triggered by COVID-19-mediated adu...

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Published in:Journal of biomedical science Vol. 28; no. 1; pp. 9 - 18
Main Authors: Trougakos, Ioannis P., Stamatelopoulos, Kimon, Terpos, Evangelos, Tsitsilonis, Ourania E., Aivalioti, Evmorfia, Paraskevis, Dimitrios, Kastritis, Efstathios, Pavlakis, George N., Dimopoulos, Meletios A.
Format: Journal Article
Language:English
Published: London BioMed Central 12.01.2021
BioMed Central Ltd
Springer Nature B.V
BMC
Subjects:
ACE2
Acute respiratory distress syndrome
Adaptive immunity
Adult respiratory distress syndrome
Age
Angiotensin II
Angiotensin-converting enzyme 2
Antigen presentation
Antigens
ARDS
Biomedical and Life Sciences
Biomedicine
Complications and side effects
Coronaviruses
COVID-19
COVID-19 - complications
COVID-19 - drug therapy
COVID-19 - physiopathology
COVID-19 - virology
Cycle ratio
Cytokine storm
Cytokines
Disease transmission
Gastrointestinal system
Gastrointestinal tract
Humans
Immune response
Immune system
Infection
Inflammation
Kidneys
Life Cycle Stages
Life cycles
Organotropism
Proto-Oncogene Mas
Review
SARS-CoV-2
SARS-CoV-2 - isolation & purification
SARS-CoV-2 - physiology
Severe acute respiratory syndrome coronavirus 2
Storm damage
TMPRSS2
Viral diseases
Viral infections
Virus diseases
Viruses
COVID-19
ACE2
TMPRSS2
SARS-CoV-2
ARDS
ISSN:1423-0127, 1021-7770, 1423-0127
Online Access:Get full text
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Summary:Background Gaining further insights into SARS-CoV-2 routes of infection and the underlying pathobiology of COVID-19 will support the design of rational treatments targeting the life cycle of the virus and/or the adverse effects (e.g., multi-organ collapse) that are triggered by COVID-19-mediated adult respiratory distress syndrome (ARDS) and/or other pathologies. Main body COVID-19 is a two-phase disease being marked by ( phase 1 ) increased virus transmission and infection rates due to the wide expression of the main infection-related ACE2 , TMPRSS2 and CTSB/L human genes in tissues of the respiratory and gastrointestinal tract, as well as by ( phase 2 ) host- and probably sex- and/or age-specific uncontrolled inflammatory immune responses which drive hyper-cytokinemia, aggressive inflammation and (due to broad organotropism of SARS-CoV-2) collateral tissue damage and systemic failure likely because of imbalanced ACE/ANGII/AT1R and ACE2/ANG(1–7)/MASR axes signaling. Conclusion Here we discuss SARS-CoV-2 life cycle and a number of approaches aiming to suppress viral infection rates or propagation; increase virus antigen presentation in order to activate a robust and durable adaptive immune response from the host, and/or mitigate the ARDS-related “cytokine storm” and collateral tissue damage that triggers the severe life-threatening complications of COVID-19.
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ISSN:1423-0127
1021-7770
1423-0127
DOI:10.1186/s12929-020-00703-5