The ACE2 as a “rescue protein” or “suspect enzyme” in COVID-19: possible application of the “engineered inactive hrsACE2” as a safer therapeutic agent in the treatment of SARS-CoV-2 infection

Khodarahmi, Reza; Sayad, Babak; Sobhani, Mahsa

doi:10.1007/s13738-020-02049-z

Cited by 6 publications

(9 citation statements)

References 66 publications

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“…Collectively, data suggested that the beneficial effects of APN01 can include slowing down the viral entry, spread and ultimately viral neutralization. It can also preserve cellular ACE-2, hence maintaining its protective activity to vital body organs [ 8 , 56 , 115 , 119 ].…”

Section: Potential Sars-cov-2 S Protein-based Therapiesmentioning

confidence: 99%

SARS-CoV-2 spike protein: pathogenesis, vaccines, and potential therapies

et al. 2021

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Purpose COVID-19 pandemic has emerged as a result of infection by the deadly pathogenic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causing enormous threats to humans. Coronaviruses are distinguished by a clove-like spike (S) protein, which plays a key role in viral pathogenesis, evolutions, and transmission. The objectives of this study are to investigate the distinctive structural features of SARS-CoV-2 S protein, its essential role in pathogenesis, and its use in the development of potential therapies and vaccines. Methodology A literature review was conducted to summarize, analyze, and interpret the available scientific data related to SARS-CoV-2 S protein in terms of characteristics, vaccines development and potential therapies. Results The data indicate that S protein subunits and their variable conformational states significantly affect the virus pathogenesis, infectivity, and evolutionary mutation. A considerable number of potential natural and synthetic therapies were proposed based on S protein. Additionally, neutralizing antibodies were recently approved for emergency use. Furthermore, several vaccines utilizing the S protein were developed. Conclusion A better understanding of S protein features, structure and mutations facilitate the recognition of the importance of SARS-CoV-2 S protein in viral infection, as well as the development of therapies and vaccines. The efficacy and safety of these therapeutic compounds and vaccines are still controversial. However, they may potentially reduce or prevent SARS-CoV-2 infection, leading to a significant reduction of the global health burden of this pandemic.

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Section: Potential Sars-cov-2 S Protein-based Therapiesmentioning

confidence: 99%

SARS-CoV-2 spike protein: pathogenesis, vaccines, and potential therapies

et al. 2021

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“…Since ACE2 inhibitors and Ang II AT1 receptor antagonists have the potential to increase ACE2 expression, which may aggravate COVID-19, we recommend critical publications regarding the use of renin-angiotensin inhibitors and COVID-19 ( Bavishi et al, 2020 ; Peiró and Moncada, 2020 ; Sanchis-Gomar et al, 2020 ; Sommerstein et al, 2020 ; Vaduganathaan et al, 2020 ). Yet the presence of the soluble and active isoform of ACE2 may be beneficial in COVID-19 patients since soluble ACE2 may compete with the membrane enzyme, limiting its role as a SARS-CoV-2 receptor, and decreasing the Ang II plasma levels ( Khodarahmi et al, 2021 ). As a therapeutic target, the restoration of ACE2 through the administration of recombinant ACE2 may reverse the lung-injury process ( Monteil et al, 2020 , 2021 ; Siriwattananon et al, 2021 ; Zhang et al, 2021 ).…”

Section: Angiotensin-converting Enzyme 2 and The Implication Of The R...mentioning

confidence: 99%

Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Pregnancy. A Non-systematic Review of Clinical Presentation, Potential Effects of Physiological Adaptations in Pregnancy, and Placental Vascular Alterations

et al. 2022

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In December 2019, the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) rapidly spread to become a pandemic. To date, increasing evidence has described the potential negative impact of SARS-CoV-2 infection on pregnant women. Although the pathophysiology of coronavirus disease 2019 (COVID-19) is not entirely understood, there is emerging evidence that it causes a severe systemic inflammatory response associated with vascular alterations that could be of special interest considering some physiological changes in pregnancy. Additionally, these alterations may affect the physiology of the placenta and are associated with pregnancy complications and abnormal histologic findings. On the other hand, data about the vaccine against SARS-CoV-2 are limited, but the risks of administering COVID-19 vaccines during pregnancy appear to be minimal. This review summarizes the current literature on SARSCoV2 virus infection, the development of COVID-19 and its relationship with physiological changes, and angiotensin-converting enzyme 2 (ACE2) function during pregnancy. We have particularly emphasized evidence coming from Latin American countries.

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“…On the other hand, SARS‐CoV‐2 downregulates ACE2 and reduces Ang (1–7) after infection. As a result, the high severity and high mortality rate among these patients could be due to reasons, such as vasoconstriction, vascular damage, fibrosis, proliferation, and inflammation due to reduction of Ang (1–7) 3 …”

Section: Introductionmentioning

confidence: 99%

“…1 Ang (1-7) exerts vasodilation, vascular protection, anti-fibrosis, antiproliferation, and anti-inflammation actions. The heart, brain, and kidney are major sources to produce Ang (1)(2)(3)(4)(5)(6)(7). This peptide as a vasodilator agent plays an important role in improving heart and lung functions.…”

mentioning

confidence: 99%

“…As a result, the high severity and high mortality rate among these patients could be due to reasons, such as vasoconstriction, vascular damage, fibrosis, proliferation, and inflammation due to reduction of Ang (1-7). 3 Given the key role of ACE2 in infection of the virus and the protective roles of Ang (1-7) as its product, we hypothesized that there was an indirect relationship between Ang (1-7) level and disease severity in patients with COVID-19.…”

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confidence: 99%

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Patients with severe COVID‐19 have reduced circulating levels of angiotensin‐(1–7): A cohort study

Seyedmehdi

Imanparast

Mohaghegh

et al. 2022

Health Science Reports

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Background and Aims Angiotensin‐converting enzyme 2 (ACE2) acts as a functional receptor for the entry of severe acute respiratory syndrome coronavirus 2 into host cells. Angiotensin (1–7) (Ang (1–7)) obtained from the function of ACE2 improves heart and lung function. We investigated the relationship between Ang (1–7) level and disease severity in patients with coronavirus disease 2019 (COVID‐19). Methods This cohort study was carried out at Masih Daneshvari Hospital in Tehran, Iran from September 2020 to October 2020. To do so, the Ang (1–7) levels of 331 hospitalized COVID‐19 patients with and without underlying disease were measured by ELISA kit. The need for oxygen, intubation, and mechanical ventilation were recorded for all the patients. Results Results showed a significant inverse relationship between the levels of Ang 1–7 and the severity of the disease (needed oxygen, intubation, and mechanical ventilation). According to the results, median (interquartile range) of Ang (1–7) levels was significantly lower in patients who needed oxygen versus those who needed no oxygen (44.50 (91) vs. 82.25 (68), p = 0.002), patients who needed intubation and mechanical ventilation versus those who did not (9.80 (62) vs. 68.70 (102), p < 0.000) and patients hospitalized in an intensive care unit (ICU) than people hospitalized in other wards. We also found that the older patients were more in need of ICU and mechanical ventilation than younger patients. Conclusions Higher levels of Ang (1–7) have been associated with decreased disease severity. Besides this, we perceived that synthetic Ang 1–7 peptides may be useful to treat and reduce the complications of COVID‐19.

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The ACE2 as a “rescue protein” or “suspect enzyme” in COVID-19: possible application of the “engineered inactive hrsACE2” as a safer therapeutic agent in the treatment of SARS-CoV-2 infection

Cited by 6 publications

References 66 publications

SARS-CoV-2 spike protein: pathogenesis, vaccines, and potential therapies

SARS-CoV-2 spike protein: pathogenesis, vaccines, and potential therapies

Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Pregnancy. A Non-systematic Review of Clinical Presentation, Potential Effects of Physiological Adaptations in Pregnancy, and Placental Vascular Alterations

Patients with severe COVID‐19 have reduced circulating levels of angiotensin‐(1–7): A cohort study

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