Itt írjon a(z) Covid_ACE-ról/ről

COVID and ACE receptors

Jung Min Sun , Oh Yuri , Song Bo Eun

CONTENTS

I. Intro

3 1. COVID

3 2. ACE receptors

3 3. Relations between COVID and ACE receptors

3 4. Pathological aspects

3 II. Body

3 III. Conclusion

3 1. Summary

3 2. Expectations

3 IV. Citation 3

Intro

COVID

COVID is a type of virus. Therefore, it can replicate within a host organism such as bacteria, plants, and animals, and cause a variety of diseases. It is identified in 2019, as SARS-CoV-2, or COVID-19. Since then, it has caused a severe pandemic of respiratory illness all over the world. By February 2022, the total number of positive cases is about 440 million, of which about 6 million have died. COVID-19 symptoms include cough, fever or chills, shortness of breath or difficulty breathing, muscle or body aches, sore throat, the new loss of taste or smell, diarrhea, headache, new fatigue, nausea or vomiting, and congestion or runny nose. (Symptoms of COVID-19, 2022) Some people infected with the coronavirus have mild COVID-19 illness, and others have no symptoms at all. In some cases, however, COVID-19 can lead to respiratory failure, lasting lung, and heart muscle damage, nervous system problems, kidney failure, or death. (What Is Coronavirus? 2022)

ACE receptors

Angiotensin-converting enzyme(ACE) has a significant role in SARS-CoV-2 virus entry. ACE receptor is a key component of the renin-angiotensin system which regulates blood pressure by controlling the volume of the fluid. It indirectly increases blood pressure by causing vasoconstriction. Also ACE acts on the kinin kallikrein system where it degrades bradykinin, a vasodilator. “ACE2, angiotensin-converting enzyme 2, is a protein on the surface of many cell types. It is an enzyme that generates small proteins – by cleaving up the larger protein angiotensinogen – that then go on to control functions in the cell.” (What is the ACE2 receptor, 2021) Using the spike-like protein on its surface of the SARS-CoV-2 virus, it binds to ACE2. They act as lock and key model.This is processed by transmembrane protease-serine2 prior to the entry and infection of cells. Hence, ACE2 acts as a cellular doorway – a receptor –to invade target cells causing symptoms of COVID-19. Organs with high amounts of ACE2 proteins tend to be infected SARS-CoV-2 easily. This virus diffuses and transmits through the human respiratory system. Thus, the lung is the primary and principal organ of SARS-CoV-2 infection.

Relations between COVID and ACE receptors

ACE2 is a protein which serves as the entry point for the SARS-CoV-2 virus to anchor and infect the cells. ACE2 is a negative regulator of the renin-angiotensin-aldosterone system(RAAS). RAAS is a hormone system that regulates blood pressure and water/electrolyte balance. The SARS-CoV-2 virus binds with ACE2 to enter the targeted cells and elicits ACE/ACE2 ratio balance disruption and RAAS activation. In most pathological conditions, there is an increase in the ACE/ACE2 ratio within the organs and system. This ratio imbalance is often due to the downregulation of ACE levels and it is accompanied by a disturbance in RAAS homeostasis. It may be responsible for the high risk of having a worse outcome in COVID19 infection. Such as respiratory failure, lasting lung, and heart muscle damage, nervous system problems, kidney failure, or death. (What Is Coronavirus? 2022)

Pathological aspects

The virus spreads mainly from person to person who is in close contact with each other, usually at a conversational distance, so it is important to have a social distance between each person which is 1.5m. “The virus can spread from an infected person’s respiratory system by mouth or nose in small liquid particles when they use them for example, cough, sneeze, speak, sing or breathe. The heavy droplets drop onto the ground, but small particles remain in the air. Another person can then attract the virus when infectious particles that pass through the air are inhaled at a short-distance” (this is often called short-range aerosol or short-range airborne transmission) (Coronavirus disease (COVID-19): How is it transmitted? 2022) or if infectious particles come into direct contact with the eyes, nose, or mouth (droplet transmission). The virus can also spread easily if it is poorly ventilated or crowded with many people, where people tend to have short individual spaces and they spend longer periods of time. “This is because aerosols can remain suspended in the air or travel farther than conversational distance (this is often called long-range aerosol or long-range airborne transmission). People may also become infected when touching their faces because eyes, nose, or mouth are easy to get infected after touching surfaces or objects that have been contaminated by the virus.” (Coronavirus, 2022) On 23 February 2020, according to WHO, they had not mentioned transmission by means of aerosols. This defines that the virus can be spread from one to branch other by distances of more than one meter or remain in the air. so according to nature.com “Early in the pandemic, the World Health Organization stated that SARS-CoV-2 was not transmitted through the air. That mistake and the prolonged process of correcting it sowed confusion and raised questions about what will happen in the next pandemic.”

Therefore, it is widely known that the best way to protect themselves is to get vaccinated and boosted, wear masks, wash their hands, practice physical distancing, and so on. Here, numerous scientists and engineers come up with innovative hypotheses. Among them, there is an interesting hypothesis about the ACE receptor inferred by its characteristics. An imbalance in the ACE/ACE2 ratio may be a cause of the worsening of COVID-19. In other words, a high ACE/ACE2 ratio is detrimental to COVID-19 infection. “Organs that express a high level of ACE2 are the targets of SARS-CoV-2 infection. This virus diffuses and transmits through the human respiratory system. Thus, the lung is the primary and principal organ of SARS-CoV-2 infection.” (Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19, 2021) However, it has been suggested that the increased concentration of ACE2 receptors in the lungs may have a protective effect on severe clinical symptoms due to SARS-CoV-2 invasion. Some data support a negative correlation between ACE2 expression and COVID19 severe outcomes. It means that the therapies reducing the ACE/ACE2 ratio are helpful for treating infected COVID19 patients.

II. Body

Angiotensin-converting enzyme 2(ACE2) is the important receptor for coronavirus and this receptor protects the lung from injury. ACE2 receptors have been identified as a key receptor for SARS-CoV-2 infections and inhibiting this process can be used as a treatment for COVID-infected patients. However, it is unclear whether human recombinant soluble ACE2(hsrACE2) prevents the growth of SARS-CoV-2. Some of the research shows that SARS-CoV-2 spike protein directly binds to ACE2. The SARS-CoV-2 virus has a high binding affinity to human ACE2. Recently, it has been figured out that the cell culture of soluble ACE2 fused to Ig or a potent serine protease inhibitor called camostat mesylate can prevent infections with a pseudovirus bearing the S protein of SARS-CoV-2. High doses of camostat mesylate were shown to partially decrease SARS-CoV-2 growth. Lung in the healthy adult, ACE2 is expressed in alveolar cells which are producing surfactant that reduces surface tension. Alveoli prevent collapse by surfactant and thus it is critical for the efficient gas exchange of the lung. Injury of the alveolar epithelial type 2 cells is able to explain the acute lung injury seen in COVID-19 patients. The ACE2 distribution on the organ can explain the multiorgan dysfunction observed in patients. A report says that the clinical-grade human recombinant soluble ACE2(hrsACE2) can decrease viral growth in Vero E6 cells. HsACE2 is being considered for the treatment of COVID19 because it can interfere with SARS-CoV-2 infections. In the experiment infected Vero-E6 cells with different numbers of SARS-CoV-2 and viral RNA are used as a marker of the replication. Infected cells with hrsACE2 show inhibited SARS-CoV-2 infections of Vero-E6 by capturing any foreign virus particles that could infect neighboring cells. An initial site of SARS-CoV-2 infection is the lung which is critical for the virus to spread to the other organs. Supernatants of infected organ cells collected on day 6 post-infection could efficiently infect Vero E6 cells visualizing that the infected capillary organoids produced virus offspring. The addition of hrsACE2 significantly reduces SARS-CoV-2 infections of the modified human blood vessels. Human capillary organoids can be infected with SARS-CoV-2 and the infection can be markedly inhibited by hrsACE2. Also, ACE2 is highly expressed in the kidney tubules. It has been shown that SARS-CoV-2 can be found in the urine. Single-cell profiling of kidney cells showed the presence of cells expressing ACE2 in the proximal tubule and podocyte 2 cell clusters that express key marker genes of proximal tubular cells and podocytes. Kidney organoids contain cell clusters that express ACE2 in a similar fashion to native tissue. The above studies were focused on the early stages of the virus infection which demonstrate that hrrACE2 can interfere with the entry of SARS-CoV-2 in the host cells. The effect of the receptor in the later stages is not known yet. The RAAS system is a complicated network of pathways that are influenced by environments. To address these problems, experiments are further conducted in vitro and in vivo.

Conclusion

Summary

Angiotensin-converting enzyme 2 (ACE2) is the key receptor for respiratory syndrome coronavirus (SARS-CoV), which causes severe failure of the lungs and death by providing the entry point of the SARS-CoV2 virus. When ACE2 levels are low and the ACE/ACE2 ratio is high we may be more at risk of having a worse outcome in Covid-19 infection. such as severe respiratory symptoms, lung, and heart muscle damage, nervous system problems, kidney failure, or death. (What Is Coronavirus? 2022)

Expectations

Many experiments against COVID-19 are now going on. Experiments related to the above mechanism are also being performed.

Citation

Monteil V, Kwon H, Prado P, Hagelkrüys A, Wimmer RA et al (May, 2020): Inhibition of SARS-COV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. National Library of Medicine. 18: (6). 905-910.

Beyerstedt, S., Casaro, E. B., & Rangel, É. B. (May, 2021): Covid-19: Angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-COV-2 infection. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. 15: (2). 913-914.

Ni, W., Yang, X., Yang, D., Bao, J., Li, R., Xiao, Y. et al (July, 2020 ). Role of angiotensin-converting enzyme 2 (ACE2) in Covid-19 - Critical Care. BioMed Central. 10: (7). 2-8

Hippisley-Cox, J., Young, D., Coupland, C., Channon, K. M. et al (October, 2020). Risk of severe COVID-19 disease with ACE inhibitors and angiotensin receptor blockers: Cohort study including 8.3 million people. BMJ journals. 9:(6). 1505-1510

Sriram, K., Insel, P., & Loomba, R. (May 14, 2020). What is the ACE2 receptor, how is it connected to coronavirus and why might it be key to treating COVID-19? The experts explain. The Conversation. https://theconversation.com/what-is-the-ace2-receptor-how-is-it-connected-to-coronavirus-and-why-might-it-be-key-to-treating-covid-19-the-experts-explain-136928

Pagliaro, P., & Penna, C. (January 1, 2019). ACE/Ace2 ratio: A key also in 2019 coronavirus disease (covid-19)? Frontiers in Medicine. 5:(4). 2-5.

A. Khan, C. Benthin, B. Zeno, T.E. Albertson, J. Boyd et al. (September, 2017)A pilot clinical trial of recombinant human angiotensin-converting enzyme 2 in acute respiratory distress syndrome. National Library of Medicine. National center for biotechnology information. 9:(6). 3-8.

H. Zhang, J.M. Penninger, Y. Li, N. Zhong, A.S. Slutsky. (April, 2020) Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. National Library of Medicine. National center for biotechnology information. 5:(2). 3-4.

W. Wang, Y. Xu, R. Gao, R. Lu, K. Han, G. Wu, W. Tan (May, 2020)Detection of SARS-CoV-2 in Different Types of Clinical Specimens. National Library of Medicine. National center for biotechnology information. 7:(4). 3-6.

U. Danilczyk, J.M. Penninger (Mar 3, 2016) Angiotensin-converting enzyme II in the heart and the kidney. Circulation research. Circulation Research. 9: (6) 463-468

Lin, W., Hu, L., Zhang, Y., Ooi, J.D., Meng, T., Jin, P., Ding, X. et al. (April 4, 2020). Single-cell Analysis of ACE2 Expression in Human Kidneys and Bladders Reveals a Potential Route of 2019-nCoV Infection. National Library of Medicine. National center for biotechnology information. 19:(5). 6-10

D. Wrapp, N. Wang, K.S. Corbett, J.A. Goldsmith, C.L. Hsieh, O. Abiona et al. (Mar 13, 2020). Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. National Library of Medicine. National center for biotechnology information. 17: (4). 1260-1263

Clarke NE, Turner AJ. (November 10, 2010). Angiotensin-converting enzyme 2: the first decade. National Library of Medicine. National center for biotechnology information. 37: (3). 8-10

Y. Imai, K. Kuba, S. Rao, Y. Huan, F. Guo, B. Guan, P. Yang et al. (July 7, 2005) Angiotensin-converting enzyme 2 protects from severe acute lung failure. National Library of Medicine. National center for biotechnology information. 16: (5). 112-116

S.A. Jeffers, S.M. Tusell, L. Gillim-Ross, E.M. Hemmila, J.E. Achenbach, G.J. Babcock et al. (November 4, 2004). CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus 23: (3). 15-17.

M. Haschke, M. Schuster, M. Poglitsch, H. Loibner, M. Salzberg et al. Pharmacokinetics and pharmacodynamics of recombinant human angiotensin-converting enzyme 2 in healthy human subjects Clin. Pharmacokinet., 52 (2013), pp. 783-792

B. Treml, N. Neu, A. Kleinsasser, C. Gritsch, T. Finsterwalder, R. Geiger, M. Schuster, E. Janzek, H. Loibner, J. Penninger, A. Loeckinger Recombinant angiotensin-converting enzyme 2 improves pulmonary blood flow and oxygenation in lipopolysaccharide-induced lung injury in piglets Crit. Care Med., 38 (2010), pp. 596-

M.A. Crackower, R. Sarao, G.Y. Oudit, C. Yagil, I. Kozieradzki, S.E. Scanga, A.J. Oliveira-dos-Santos, J. da Costa, L. Zhang, Y. Pei, et al. Angiotensin-converting enzyme 2 is an essential regulator of heart function Nature, 417 (2002), pp. 822-828

J. Gu, E. Gong, B. Zhang, J. Zheng, Z. Gao, Y. Zhong, W. Zou, J. Zhan, S. Wang, Z. Xie, et al. Multiple organ infection and the pathogenesis of SARS J. Exp. Med., 202 (2005), pp. 415-424

Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19).Bourgonje AR, Abdulle AE, Timens W, Hillebrands JL, Navis GJ, Gordijn SJ, Bolling MC, Dijkstra G, Voors AA, Osterhaus AD, van der Voort PH, Mulder DJ, van Goor H. J Pathol. 2020 Jul;251(3):228-248. doi: 10.1002/path.5471. Epub 2020 Jun 10.

SARS-CoV-2 pandemic and research gaps: Understanding SARS-CoV-2 interaction with the ACE2 receptor and implications for therapy. Datta PK, Liu F, Fischer T, Rappaport J, Qin X.Theranostics. 2020 Jun 12;10(16):7448-7464. doi: 10.7150/thno.48076. eCollection 2020.

Angiotensin-Converting Enzyme 2 (ACE2) in the Pathogenesis of ARDS in COVID-19.Kuba K, Yamaguchi T, Penninger JM.Front Immunol. 2021 Dec 22;12:732690. doi: 10.3389/fimmu.2021.732690. eCollection 2021.

Covid_ACE (last edited 2022-05-07 23:11:55 by 4566E)