SARS-CoV-2-Specific Immune Response and the Pathogenesis of COVID-19

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(3), С. 1716 - 1716

Опубликована: Фев. 2, 2022

The review aims to consolidate research findings on the molecular mechanisms and virulence pathogenicity characteristics of coronavirus disease (COVID-19) causative agent, severe acute respiratory syndrome 2 (SARS-CoV-2), their relevance four typical stages in development viral infection. These are invasion; primary blockade antiviral innate immunity; engagement virus’s protection against factors adaptive acute, long-term complications COVID-19. invasion stage entails recognition spike protein (S) SARS-CoV-2 target cell receptors, namely, main receptor (angiotensin-converting enzyme 2, ACE2), its coreceptors, potential alternative receptors. presence a diverse repertoire receptors allows infect various types cells, including those not expressing ACE2. During second stage, majority polyfunctional structural, non-structural, extra proteins synthesizes infected cells involved blockage immunity. A high degree redundancy systemic action characterizing these pathogenic overcome at initial invasion. third includes passive active virus from immunity, overcoming barrier function focus inflammation, generalization body. fourth is associated with deployment variants SARS-CoV-2’s ability induce autoimmune autoinflammatory pathways tissue both immunosuppressive hyperergic inflammation critical this

Язык: Английский

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The roles of Eph receptors, neuropilin-1, P2X7, and CD147 in COVID-19-associated neurodegenerative diseases: inflammasome and JaK inhibitors as potential promising therapies

Cellular & Molecular Biology Letters, Год журнала: 2022, Номер 27(1)

Опубликована: Фев. 2, 2022

Abstract The novel coronavirus disease 2019 (COVID-19) pandemic has spread worldwide, and finding a safe therapeutic strategy effective vaccine is critical to overcoming severe acute respiratory syndrome 2 (SARS-CoV-2). Therefore, elucidation of pathogenesis mechanisms, especially entry routes SARS-CoV-2 may help propose antiviral drugs vaccines. Several receptors have been demonstrated for the interaction spike (S) protein with host cells, including angiotensin-converting enzyme (ACE2), ephrin ligands Eph receptors, neuropilin 1 (NRP-1), P2X7, CD147. expression these in central nervous system (CNS) make CNS prone invasion, leading neurodegenerative diseases. present review provides potential pathological mechanisms infection CNS, cytokines involved neuroinflammatory conditions. Moreover, it explains several disorders associated COVID-19. Finally, we suggest inflammasome JaK inhibitors as strategies

Язык: Английский

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SARS-CoV-2 infection triggers pro-atherogenic inflammatory responses in human coronary vessels

Nature Cardiovascular Research, Год журнала: 2023, Номер 2(10), С. 899 - 916

Опубликована: Сен. 28, 2023

Abstract Patients with coronavirus disease 2019 (COVID-19) present increased risk for ischemic cardiovascular complications up to 1 year after infection. Although the systemic inflammatory response severe acute respiratory syndrome 2 (SARS-CoV-2) infection likely contributes this risk, whether SARS-CoV-2 directly infects coronary vasculature and attendant atherosclerotic plaques remains unknown. Here we report that viral RNA is detectable replicates in lesions taken at autopsy from COVID-19 cases. targeted plaque macrophages exhibited a stronger tropism arterial than adjacent perivascular fat, correlating macrophage infiltration levels. entry was cholesterol-loaded primary dependent, part, on neuropilin-1. induced robust cultured human vascular explants secretion of cytokines known trigger events. Our data establish vessels, inducing inflammation could increase long-term risk.

Язык: Английский

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An update of anti-viral treatment of COVID-19

TURKISH JOURNAL OF MEDICAL SCIENCES, Год журнала: 2021, Номер 51(SI-1), С. 3372 - 3390

Опубликована: Авг. 15, 2021

Currently there is not an effective antiviral treatment for COVID-19, but a large number of drugs have been evaluated since the beginning pandemic, and many them used COVID-19 despite preliminary or conflicting results clinical trials. We aimed to review summarize all current knowledge on antivirals COVID-19There are 2 main drug groups SARS-CoV-2: agents that target proteins RNA virus interfere with biological processes in host support virus. The include inhibitors viral entry into human cell (convalescent plasma, monoclonal antibodies, nanobodies, mini proteins, soluble ACE-2, camostat, dutasteride, proxalutamide, bromhexin, hydroxychloroquine, umifenovir nitazoxanid, niclosamide, lactoferrin), proteases (lopinavir/ritonavir, PF-07321332, PF-07304814, GC376), (remdesivir, favipiravir, molnupiravir, AT-527, merimepodib, PTC299), supporting (plitidepsin, fluvoxamine, ivermectin), natural immunity (Interferons).When taking account available laboratory trials subject, antibodies seem be most at moment, high-titer convalescent plasma also could when administered during early phase disease. As lopinavir/ritonavir, were found ineffective RCTs, they should used. Additional studies needed define role remdesivir, interferons, ivermectin, proxulutamide, bromhexine, nitazoxanide, niclosamid COVID-19. Finally, waited learn whether newer such as plitidepsin AT-527

Язык: Английский

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Covid-19-Induced Dysautonomia: A Menace of Sympathetic Storm

ASN NEURO, Год журнала: 2021, Номер 13, С. 175909142110576 - 175909142110576

Опубликована: Янв. 1, 2021

Among the plethora of debilitating neurological disorders COVID-19 syndrome in survivors, scope SARS-CoV-2-induced dysautonomia (DNS) is yet to be understood, though implications are enormous. Herein, we present an inclusive mini-review DNS and its associated complications. Although, direct link between Covid-19 DSN still speculative, hypothetical links thought either a neuronal injury autonomic pathway or para/post-infectious immune-induced mechanism. SARS-CoV-2 infection-induced stress may activate sympathetic nervous system (SNS) leading neuro-hormonal stimulation activation pro-inflammatory cytokines with further development storm. Sympathetic over-activation correlated increase capillary pulmonary leakage, alveolar damage, acute respiratory distress syndrome. Furthermore, can spread through mechanoreceptors chemoreceptors medullary center retrograde manner resulting sudden failure. Taken together, developed due storm inhibition Parasympathetic system-mediated anti-inflammatory effect cytokine Therefore, storms together Renin-Angiotensin-System chief final involved Covid-19.

Язык: Английский

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A scoping review of the pathophysiology of COVID-19

International Journal of Immunopathology and Pharmacology, Год журнала: 2021, Номер 35

Опубликована: Янв. 1, 2021

COVID-19 is a highly heterogeneous and complex medical disorder; indeed, severe probably amongst the most of conditions known to science. While enormous strides have been made in understanding molecular pathways involved patients infected with coronaviruses an overarching comprehensive pathogenesis lacking. Such essential formulation effective prophylactic treatment strategies. Based on clinical, proteomic, genomic studies as well autopsy data disease can be considered connection three basic pathologic processes, namely pulmonary macrophage activation syndrome uncontrolled inflammation, complement-mediated endothelialitis together procoagulant state thrombotic microangiopathy. In addition, platelet release serotonin degranulation mast cells contributes hyper-inflammatory state. Auto-antibodies demonstrated large number hospitalized which adds end-organ damage pro-thrombotic This paper provides clinical overview major pathogenetic mechanism leading disease.

Язык: Английский

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The Role of Neuropilin-1 (NRP-1) in SARS-CoV-2 Infection: Review

Journal of Clinical Medicine, Год журнала: 2021, Номер 10(13), С. 2772 - 2772

Опубликована: Июнь 24, 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), discovered in 2019, is responsible for the global disease 19 (COVID-19) pandemic. The main protein that interacts with host cell receptor Spike-1 (S1) subunit of coronavirus. This binds receptors present on membrane. It has been identified from several studies neuropilin-1 (NRP-1) one co-receptors SARS-CoV-2 entry. Therefore, this review, we focus significance NRP-1 infection. MEDLINE/PubMed database was used a search available literature. In current report plays many important functions, including angiogenesis, neuronal development, and regulation immune responses. Additionally, presence glycoprotein membrane significantly augments infection spread SARS-CoV-2. Literature data suggest facilitates entry virus into central nervous system through olfactory epithelium nasal cavity. Moreover, published findings show interfering VEGF-A/NRP-1 using inhibitors may produce an analgesic effect. review describes association between NRP-1, and, inter alia, pathological changes retina. Based findings, very mediator implicated in, neurological manifestations it appears use promising therapeutic strategy treatment

Язык: Английский

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Role of the Renin–Angiotensin–Aldosterone and Kinin–Kallikrein Systems in the Cardiovascular Complications of COVID-19 and Long COVID

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(15), С. 8255 - 8255

Опубликована: Июль 31, 2021

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the virus responsible for COVID-19 pandemic. Patients may present as asymptomatic or demonstrate mild to severe and life-threatening symptoms. Although has a respiratory focus, there are major cardiovascular complications (CVCs) associated with infection. The reported CVCs include myocarditis, heart failure, arrhythmias, thromboembolism blood pressure abnormalities. These occur, in part, because of dysregulation Renin–Angiotensin–Aldosterone System (RAAS) Kinin–Kallikrein (KKS). A route by which SARS-CoV-2 gains cellular entry via docking viral spike (S) protein membrane-bound angiotensin converting enzyme (ACE2). roles ACE2 within immune systems vital ensure homeostasis. key routes development recently described long COVID have been hypothesised direct consequences S protein/ACE2 axis, downregulation resulting damage inflicted response. Here, we review impact on system, mechanisms RAAS KKS can occur following infection future implications pharmacological therapies.

Язык: Английский

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SARS-CoV-2: Receptor and Co-receptor Tropism Probability

Current Microbiology, Год журнала: 2022, Номер 79(5)

Опубликована: Март 16, 2022

Язык: Английский

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Role of Neuropilin 1 in COVID-19 Patients with Acute Ischemic Stroke

Biomedicines, Год журнала: 2022, Номер 10(8), С. 2032 - 2032

Опубликована: Авг. 20, 2022

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection can trigger the adaptive and innate immune responses, leading to uncontrolled inflammatory reactions associated local systematic tissue damage, along with thromboembolic disorders that may increase risk of ischemic stroke (AIS) in COVID-19 patients. The neuropilin (NRP-1) which is a co-receptor for vascular endothelial growth factor (VEGF), integrins, plexins, involved pathogenesis AIS. NRP-1 also regarded as entry SARS-CoV-2 facilitates its into brain through olfactory epithelium. cofactor binding angiotensin-converting enzyme (ACE2), since absence ACE2 reduces infectivity even presence NRP-1. Therefore, aim present study was clarify potential role patients transmit epithelium nasal cavity, different neurological disorders, therefore about 45% had manifestations. has capability attenuate neuroinflammation, blood-brain barrier (BBB) permeability, cerebral dysfunction (ED), neuronal are uncommon involvement, including Similarly, high serum level linked ED, oxidative stress, pulmonary thrombosis severe COVID-19, suggesting compensatory mechanism overcome immuno-inflammatory disorders. In conclusion, an important AIS, could be biomarker linking development AIS COVID-19. findings cannot provide final thus silico, experimental, vitro, vivo, preclinical, clinical studies recommended confirm elucidate pharmacological receptor agonists antagonists

Язык: Английский

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