ACE2, Much More Than Just a Receptor for SARS-COV-2

Samavati, Lobelia; Uhal, Bruce D.

doi:10.3389/fcimb.2020.00317

Cited by 328 publications

(316 citation statements)

References 88 publications

(111 reference statements)

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“…This process leads to shedding of host ACE2 receptor and the loss of ACE2 function [22]. Because ACE2 counterbalances the deleterious effect of the RAAS, through effect of Angiotensin [1][2][3][4][5][6][7]36,37], the loss of ACE2 function amplifies the deleterious effect of angiotensin II (Ang II). It has been shown that Ang II stimulation leads to increased platelet size and activation, and that aspirin does not prevent such activation [16,38].…”

Section: Discussionmentioning

confidence: 99%

Platelets and renal failure in the SARS-CoV-2 syndrome

et al. 2020

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The coronavirus disease 19 (COVID-19) is a highly transmittable viral infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 utilizes metallocarboxyl peptidase angiotensin receptor (ACE) 2 to gain entry into human cells. Activation of several proteases facilitates the interaction of viral spike proteins (S1) and ACE2 receptor. This leads to cleavage of host ACE2 receptors. ACE2 activity counterbalances the angiotensin II effect, its loss may lead to elevated angiotensin II levels with modulation of platelet function, size and activity. COVID-19 disease encompasses a spectrum of systemic involvement far beyond respiratory failure alone. Several features of this disease, including the etiology of acute kidney injury (AKI) and the hypercoagulable state, remain poorly understood. Here, we show that there is a high incidence of AKI (81%) in the critically ill adults with COVID-19 in the setting of elevated D-dimer, elevated ferritin, C reactive protein (CRP) and lactate dehydrogenase (LDH) levels. Strikingly, there were unique features of platelets in these patients, including larger, more granular platelets and a higher mean platelet volume (MPV). There was a significant correlation between measured D-dimer levels and MVP; but a negative correlation between MPV and glomerular filtration rates (GFR) in critically ill cohort. Our data suggest that activated platelets may play a role in renal failure and possibly hypercoagulability status in COVID19 patients.

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Section: Discussionmentioning

confidence: 99%

Platelets and renal failure in the SARS-CoV-2 syndrome

et al. 2020

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“…The S protein, thus, loses its partners to enter the host cell, as illustrated on the right side of Figure 4 . ACE2 can be a target for inhibiting the entry of SARS-CoV-2 into the host cell because the binding affinity of the S protein of SARS-CoV-2 to the ACE2 receptor is 10–20-fold stronger than that of the S protein of SARS-CoV [ 68 , 69 , 70 ].…”

Section: Angiotensin-converting Enzyme 2 (Ace2)mentioning

confidence: 99%

Natural Flavonoids as Potential Angiotensin-Converting Enzyme 2 Inhibitors for Anti-SARS-CoV-2

et al. 2020

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Over the years, coronaviruses (CoV) have posed a severe public health threat, causing an increase in mortality and morbidity rates throughout the world. The recent outbreak of a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the current Coronavirus Disease 2019 (COVID-19) pandemic that affected more than 215 countries with over 23 million cases and 800,000 deaths as of today. The situation is critical, especially with the absence of specific medicines or vaccines; hence, efforts toward the development of anti-COVID-19 medicines are being intensively undertaken. One of the potential therapeutic targets of anti-COVID-19 drugs is the angiotensin-converting enzyme 2 (ACE2). ACE2 was identified as a key functional receptor for CoV associated with COVID-19. ACE2, which is located on the surface of the host cells, binds effectively to the spike protein of CoV, thus enabling the virus to infect the epithelial cells of the host. Previous studies showed that certain flavonoids exhibit angiotensin-converting enzyme inhibition activity, which plays a crucial role in the regulation of arterial blood pressure. Thus, it is being postulated that these flavonoids might also interact with ACE2. This postulation might be of interest because these compounds also show antiviral activity in vitro. This article summarizes the natural flavonoids with potential efficacy against COVID-19 through ACE2 receptor inhibition.

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“…Downregulation of ACE2 and elevated plasma angiotensin II level have been observed after SARS-CoV, SARS-CoV-2 or influenza infection, contributing to hyper-activated RAS cascades and ARDS [18][19][20]22,52 . Supplementing soluble ACE2 can balance RAS and improve ARDS conditions 17,[21][22][23]52,53 . These factors all seem to support the beneficial effects of the biological function of ACE2 for treating COVID-19 patients even though further studies are still needed to confer this advantage.…”

Section: Several Engineered Ace2 Proteins Bearing Different Number Ofmentioning

confidence: 99%

Engineered Trimeric ACE2 Binds and Locks “Three-up” Spike Protein to Potently Inhibit SARS-CoVs and Mutants

Guo

Wang

et al. 2020

Preprint

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SARS-CoV-2 enters cells via ACE-2, which binds the spike protein with moderate affinity. Despite a constant background mutational rate, the virus must retain binding with ACE2 for infectivity, providing a conserved constraint for SARS-CoV-2 inhibitors. To prevent mutational escape of SARS-CoV-2 and to prepare for future related coronavirus outbreaks, we engineered a de novo trimeric ACE2 (T-ACE2) protein scaffold that binds the trimeric spike protein with extremely high affinity (KD < 1 pM), while retaining ACE2 native sequence. T-ACE2 potently inhibits all tested pseudotyped viruses including SARS-CoV-2, SARS-CoV, eight naturally occurring SARS-CoV-2 mutants, two SARSr-CoVs as well as authentic SARS-CoV-2. The cryo-EM structure reveals that T-ACE2 can induce the transit of spike protein to “three-up” RBD conformation upon binding. T-ACE2 thus represents a promising class of broadly neutralizing proteins against SARS-CoVs and mutants.

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ACE2, Much More Than Just a Receptor for SARS-COV-2

Cited by 328 publications

References 88 publications

Platelets and renal failure in the SARS-CoV-2 syndrome

Platelets and renal failure in the SARS-CoV-2 syndrome

Natural Flavonoids as Potential Angiotensin-Converting Enzyme 2 Inhibitors for Anti-SARS-CoV-2

Engineered Trimeric ACE2 Binds and Locks “Three-up” Spike Protein to Potently Inhibit SARS-CoVs and Mutants

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