Deciphering the molecular downstream consequences of severe acute respiratory syndrome coronavirus (SARS-CoV)− 2 infection is important for a greater understanding of the disease and treatment planning. Furthermore, greater understanding of the underlying mechanisms of diagnostic and therapeutic strategies can help in the development of vaccines and drugs against COVID-19. At present, the molecular mechanisms of SARS-CoV-2 in the host cells are not sufficiently comprehended. Some of the mechanisms are proposed considering the existing similarities between SARS-CoV-2 and the other members of the β-CoVs, and others are explained based on studies advanced in the structure and function of SARS-CoV-2. In this review, we endeavored to map the possible mechanisms of the host response following SARS-CoV-2 infection and surveyed current research conducted by in vitro, in vivo and human observations, as well as existing suggestions. We addressed the specific signaling events that can cause cytokine storm and demonstrated three forms of cell death signaling following virus infection, including apoptosis, pyroptosis, and necroptosis. Given the elicited signaling pathways, we introduced possible pathway-based therapeutic targets; ADAM17 was especially highlighted as one of the most important elements of several signaling pathways involved in the immunopathogenesis of COVID-19. We also provided the possible drug candidates against these targets. Moreover, the cytokine-cytokine receptor interaction pathway was found as one of the important cross-talk pathways through a pathway-pathway interaction analysis for SARS-CoV-2 infection. Graphical Abstract ga1
【저자키워드】 COVID-19, SARS-CoV-2, COVID-19, Coronavirus disease 2019, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2, drug targets, ACE2, Angiotensin-converting enzyme-2, ARDS, acute respiratory distress syndrome, TNF-α, tumor necrosis factor alpha, RAS, Renin-angiotensin system, TMPRSS2, Transmembrane Protease Serine 2, PRRs, Pattern Recognition Receptors, ACE, angiotensin-converting enzyme, MAPKs, mitogen-activated protein kinases, TLRs, Toll-like receptors, NF-κB, nuclear factor κB, AT1R, angiotensin II type 1 receptor, JNK, Jun N-terminal kinase, ERK, Extracellular signal regulated kinase, PARP-1, Poly ADP-ribose polymerase-1, PARG, Poly (ADP-ribose) glycohydrolase, TRPM2, Transient receptor potential melastatin type 2, ADAM17, A disintegrin and metalloproteinase 17, PAMP, Pathogen-associated molecular patterns, JAK/STAT, Janus kinase/signal transducer and activator of transcription, mTOR, Mammalian target of rapamycin, HIF-1, Hypoxia-inducible factor 1, NLRP3, NOD-like receptor family pyrin domain containing 3, Molecular pathway,