Accepted Jul 7. Copyright © Springer Nature Switzerland AG This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source.
Thomas R Branson - Google Academic
This article has been cited by other articles in PMC. The S protein on the surface of the virus is cleaved by host proprotein convertases PCs to bacterial toxins in the blood the active N-terminal S1 extracellular domain. Its receptors are angiotensin-converting enzyme 2 ACE2and the C-terminal S2 membrane anchoring protein is responsible for translocating the virus into the cell.
There is currently no specific and effective targeted treatment. By exploring the theoretical analysis of PCs and ACE2 in COVID cardiovascular susceptibility, some insights on how to prevent and alleviate adverse cardiovascular prognosis have been provided in this study.
Current clinical reports indicate that SARS-CoV-2 is associated with significant morbidity of cardiovascular diseases and complications, such as hypertension HTNmyocarditis, acute myocardial infarction, and increased heart failure [ 56 ].
Researchers have extensively studied the pathophysiology of SARS-CoV-2 infection and believe that the Bacterial toxins in the blood receptor acts as a high-affinity receptor and co-transporter of the virus into the cell [ 78 ]. The widespread expression of ACE2 in the myocardium and vascular endothelial cells might be due bacterial toxins in the blood the presence of SARS-CoV-2, which could cause direct cardiovascular damage and lead to adverse consequences [ 69 ].
Coronavirus S protein is a granule-shaped polygemma limfa protein with a length of about aa, which helps the virus to bind to cell receptors and participate in mediating viral infection and pathogenesis [ 1112 ].
Therefore, PCs family, especially furin, can be considered the key medium that mediates the maturation of S protein processing and recognition of membrane proteins.
This speculation is also supported by the occurrence of a high level of furin in the peripheral blood of heart failure patients. Numerous studies discussed ACE2 before, and therefore this article has focused on the role of furin in this pathological process. Patients with severe infections usually present with acute respiratory distress syndrome ARDS and septic shock.
The cardiovascular system involvement bacterial toxins in the blood this infection is also a significant feature.
Ai fost blocat(ă) temporar
Cancer de prostata libros also has cardiovascular comorbidities, especially in cases with more severe conditions.
There were patients with hypertension, accounting for Besides, some patients showed symptoms of palpitations. In a study of patients, 7. However, the mechanism of these associations is currently unclear.
Proprotein Convertases and S Protein The processing and activation of the coronavirus S protein are critical to the infectivity of the virus. Therefore, relevant enzymes constitute potential targets for antiviral intervention. The proprotein convertase family PCs; gene name PCSKs is composed of nine serine-secreting proteases and is widely involved in regulating various biological processes in normal and disease states. The PCs can perform multiple activation functions and are involved in many key cellular pathways.
The PCs cleave precursor proteins at specific single or paired basic amino acids aaturning them precursor proteins into an active state. In many PCs, the processed substrate is the infectious virus cell surface glycoproteins [ 23 ].
Involvement of Spike Protein, Furin, and ACE2 in SARS-CoVRelated Cardiovascular Complications
The relationship between PCs bacterial toxins in the blood furin and viral infection was confirmed based on their role in the processing of many essential cell surface proteins [ 24 ]. This further confirms the role of PCs in the mechanism of coronavirus infection.
Therefore, the PCs family, especially furin, can be regarded as a key medium that mediates the processing and maturation of viral spike protein and recognizes membrane proteins and plays an important role in the treatment process of viral infection [ 2728 ].
The biological process of Furin processing and activation of coronavirus S protein to expose the reactive domain also explains partially the phenomenon of COVID with severe cardiovascular damage.
Furthermore, heart failure, accompanied by a marked increase in the level of furin in the peripheral blood in the course of COVID in patients [ 29 ], makes this conjecture more credible. Therefore, inhibition of such processing enzymes could represent a potential antiviral strategy.
Нет, это не совсем так; мы рассчитываем, что члены каждой группы в конечном счете окажутся счастливее именно в тех условиях, где им предстоит жить.
Interestingly, members of the PCs family often cause functional redundancy or complementation due to the high structural similarity [ 30 ].
PCSK6 functions as a critical protease for processing corin and is involved in the regulation of enkephalin blood pressure [ 32 ]. It has also been shown to be involved in the pathological process of atherosclerosis and myocardial fibrosis after myocardial infarction [ 33 ]. Therefore, furin is likely to be a functional complementarity or redundancy of PCSK6. Blocking the activity of these enzymes can reduce viral infections and cardiovascular damage and is beneficial for the treatment of cardiovascular diseases.
Besides, to limit viral infection, host cells infected by the virus can cause an interferon response, which autonomously inhibits the enzyme activity of furin [ 34 ]. Moreover, based on the role of furin protein in cardiovascular disease, its inhibitors might also improve cardiovascular prognosis and reduce critical deaths.
Therefore, furin could be a promising target for the development of new treatments. Pathogens or their toxins require processing by host PCs to enter host cells and cause disease. Conversely, inhibiting PCs may protect host cells from furin-dependent pathogens.
endotoxemic - Traducere în română - exemple în engleză | Reverso Context
The correctness of the concept of furin-dependent infection has been supported by many basic studies [ 35 — 37 ]. Various methods have been proposed that inhibit furin activity hence limiting viral and bacterial infections and tumor growth.
The variant of natural serine protease inhibitor α-1 antitrypsin affects the replication of the HIV-1 virus by interfering with the differentiation and maturation of gp to gp and gp41 [ 38 ]. Also, the clarification of the crystal structure of furin promotes the design of 2,5-dideoxystreptamine derivative inhibitors [ 3940 ]. Nevertheless, because furin is involved in many cellular processes, it is important to avoid this systemic inhibition as it can cause some toxicity.
Therefore, rapid screening of small molecule inhibitors or other more effective oral active inhibitors, such as Andrographis paniculata [ 41 ], should be conducted to evaluate its antiviral effect on nCoV. The abnormal expression or activity of furin can cause a variety of diseases that include infectious viral or bacterial infections and non-infectious diseases, metabolic diseases, and even cancer [ 34 ].
Although furin has been regarded as a potential therapeutic target for infectious diseases, the use of host protease inhibitors especially inhibitors against furin as a treatment strategy for COVID seems to be premature. S Protein and ACE2 For coronavirus to enter the host target cell, it needs to complete two key steps.
Выдавила. - Мы знаем, мама, - ответил Патрик. "Как могут они знать.
It first binds to the cell bacterial toxins in the blood by attaching to the host cell receptor and then fuses its envelope to the cell bacterial toxins in the blood for the viral genome to be bacterial toxins in the blood into the cytoplasm of the host cell to achieve viral replication. Both of these steps are controlled by the S envelope protein [ 42 ].
S protein is a structural protein of about aa in length that constitutes the corona shape of coronavirus particles. It binds to the cell receptors and participates in mediating viral infection and pathogenesis [ 43 ]. However, in the process of infection, the S protein plays a direct damaging role by recognizing and binding to the ACE2 receptor and invading the host cell [ 10 ]. Based on the high expression of ACE2 in cardiomyocytes, it is theoretically speculated that many new coronaviruses could directly bind to ACE2 and directly damage cardiomyocytes.
Referințe bibliografice pe an
AngII, as an inflammatory factor regulatory protein, plays an essential regulatory role in mediating myocardial injury, and ACE2 has a protective effect in organs such as the heart and kidney [ 45 ]. Drug analysis in hypertensive-positive patients found no association between any single drug category and the increased likelihood of positive tests.
At the same time, no drug is associated with a significant increase in the risk of serious diseases. The current beneficial effects on patients with diabetes, chronic kidney disease, and proteinuria or proteinuria exceed the theoretical risk.
The use of BCAP and rhACE2 can eliminate the membrane-anchoring domain to inhibit angiotensin II induction, high blood pressure, myocardial hypertrophy, and fibrosis, which in turn shows beneficial effects in disease models such as heart failure, acute lung injury, and diabetic nephropathy. This destroys the ability of the virus to infect the cell to the same extent leading to reduced bacterial toxins in the blood replication in the lungs and other organs.
Conclusion At present, there is still a lack of in-depth research on the complete pathophysiological process of COVID and cardiovascular disease. The lack of a specific antiviral drug means that the infected people cannot be treated and poses difficulties in controlling the spread of the virus.
Although clinical trials of antiviral drug candidates HIV protease inhibitors lopinavir and ritonavir were conducted early in the outbreak, the test results were unfortunately disappointing. Chloroquine and hydroxychloroquine are not beneficial and increase the risk of arrhythmia or even death. It is still necessary to continue to test and apply the currently available and future therapies of COVID Therefore, in patients with SARS-CoV-2 infection, transient regulation of the bacterial toxins in the blood binding sites on ACE2 or furin through immunological or pharmacological methods may constitute a new therapeutic strategy to deal with this unprecedented and powerful virus threat.
Aceste exemple pot conține termeni colocviali. Traducere "endotoxemic" în română Alte traduceri To restrict the indications of Dolovet to only those that were tested endotoxemic mastitis control would be inappropriate.