TY - JOUR
TI - Insights to SARS-CoV-2 life cycle, pathophysiology, and rationalized treatments that target COVID-19 clinical complications
AU - Trougakos, I.P.
AU - Stamatelopoulos, K.
AU - Terpos, E.
AU - Tsitsilonis, O.E.
AU - Aivalioti, E.
AU - Paraskevis, D.
AU - Kastritis, E.
AU - Pavlakis, G.N.
AU - Dimopoulos, M.A.
JO - Journal of Biomedical Science
PY - 2021
VL - 28
TODO - 1
SP - null
PB - BioMed Central Ltd.
SN - 1021-7770, 1423-0127
TODO - 10.1186/s12929-020-00703-5
TODO - angiotensin 1 receptor;  angiotensin converting enzyme 2;  angiotensin II;  angiotensin[1-7];  anticoagulant agent;  camostat mesilate;  chloroquine;  coronavirus nucleocapsid protein;  dipeptidyl carboxypeptidase;  HLA antigen class 2;  hydroxychloroquine;  interferon regulatory factor 7;  interleukin 6;  interleukin 8;  MAS receptor;  neutralizing antibody;  RNA directed RNA polymerase;  SARS-CoV-2 vaccine;  toll like receptor 3;  transcription factor Nrf2;  transmembrane protease serine 2;  tumor necrosis factor;  virus antigen;  vitronectin, ACE2 gene;  adaptive immunity;  adult respiratory distress syndrome;  amino terminal sequence;  antigen presentation;  binding affinity;  binding site;  bioaccumulation;  CD8+ T lymphocyte;  clinical effectiveness;  convalescent plasma therapy;  coronavirus disease 2019;  cross reaction;  CTSB L gene;  cytokine storm;  disease association;  disease severity;  disseminated intravascular clotting;  down regulation;  enzyme binding;  gene;  gene expression;  gene replication;  high risk patient;  human;  humoral immunity;  infection risk;  life cycle;  nonhuman;  priority journal;  protein cleavage;  protein depletion;  protein expression;  protein glycosylation;  randomized controlled trial (topic);  Review;  seroprevalence;  Severe acute respiratory syndrome coronavirus 2;  signal transduction;  TMPRSS2 gene;  venous thromboembolism;  viral tropism;  virus entry;  virus pathogenesis;  virus replication;  virus transmission;  complication;  drug therapy;  isolation and purification;  life cycle stage;  pathophysiology;  physiology;  virology, COVID-19;  Humans;  Life Cycle Stages;  SARS-CoV-2
TODO - 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. © 2021, The Author(s).
ER -