Acute Pancreatitis in a Patient With COVID-19 After the Resolution of Respiratory Symptoms

The gastrointestinal (GI) involvement, including acute pancreatitis (AP) from the novel coronavirus disease-2019 (COVID-19), is increasingly being reported. Recent evidence suggests that the pathogenesis of COVID-19 is mediated by the angiotensin-converting enzyme 2 (ACE-2) receptors and transmembrane protease serine 2 (TMPRSS2) for “priming,” which is highly expressed in the pancreas. To our knowledge, there is no other reported case of AP associated with COVID-19 after the respiratory symptoms are resolved. In this article, we present a patient with COVID-19, who came with intractable epigastric pain and resolved respiratory symptoms. A diagnosis of AP complicated with COVID-19 was made after laboratory and imaging workup, which was successfully managed conservatively.

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ACE2 Nascence, trafficking, and SARS-CoV-2 pathogenesis: the saga continues

Human Genomics ◽

10.1186/s40246-021-00304-9 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Sally Badawi ◽

Bassam R. Ali

Keyword(s):

Cell Surface ◽

Angiotensin Converting Enzyme ◽

The Novel ◽

Converting Enzyme ◽

Post Translational Modifications ◽

Angiotensin Converting Enzyme 2 ◽

Viral Attachment ◽

Novel Coronavirus ◽

Effective Medication ◽

Potential Use

AbstractWith the emergence of the novel coronavirus SARS-CoV-2 since December 2019, more than 65 million cases have been reported worldwide. This virus has shown high infectivity and severe symptoms in some cases, leading to over 1.5 million deaths globally. Despite the collaborative and concerted research efforts that have been made, no effective medication for COVID-19 (coronavirus disease-2019) is currently available. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) as an initial mediator for viral attachment and host cell invasion. ACE2 is widely distributed in the human tissues including the cell surface of lung cells which represent the primary site of the infection. Inhibiting or reducing cell surface availability of ACE2 represents a promising therapy for tackling COVID-19. In this context, most ACE2–based therapeutic strategies have aimed to tackle the virus through the use of angiotensin-converting enzyme (ACE) inhibitors or neutralizing the virus by exogenous administration of ACE2, which does not directly aim to reduce its membrane availability. However, through this review, we present a different perspective focusing on the subcellular localization and trafficking of ACE2. Membrane targeting of ACE2, and shedding and cellular trafficking pathways including the internalization are not well elucidated in literature. Therefore, we hereby present an overview of the fate of newly synthesized ACE2, its post translational modifications, and what is known of its trafficking pathways. In addition, we highlight the possibility that some of the identified ACE2 missense variants might affect its trafficking efficiency and localization and hence may explain some of the observed variable severity of SARS-CoV-2 infections. Moreover, an extensive understanding of these processes is necessarily required to evaluate the potential use of ACE2 as a credible therapeutic target.

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The Impact of Angiotensin-Converting Enzyme 2 (ACE2) Expression on the Incidence and Severity of COVID-19 Infection

Pathogens ◽

10.3390/pathogens10030379 ◽

2021 ◽

Vol 10 (3) ◽

pp. 379

Author(s):

Ahmed O. Kaseb ◽

Yehia I. Mohamed ◽

Alexandre E. Malek ◽

Issam I. Raad ◽

Lina Altameemi ◽

...

Keyword(s):

Angiotensin Converting Enzyme ◽

Preventive Measures ◽

Vulnerable Groups ◽

The Novel ◽

Converting Enzyme ◽

Potential Therapeutic Target ◽

Angiotensin Converting Enzyme 2 ◽

Incidence And Mortality ◽

Novel Coronavirus ◽

The Impact

The novel coronavirus disease 2019 (COVID-19) pandemic has led to an unprecedented threat to the international community and raised major concerns in terms of public health safety. Although our current understanding of the complexity of COVID-19 pathogenesis remains limited, the infection is largely mediated by the interaction of viral spike protein and angiotensin-converting enzyme 2 (ACE2). The functional importance of ACE2 in different demographic and comorbid conditions may explain the significant variation in incidence and mortality of COVID-19 in vulnerable groups, and highlights its candidacy as a potential therapeutic target. We provide evidence supporting the idea that differences in incidence and severity of COVID-19 infection may be related to ACE2. Emerging data based on the prevalence and severity of COVID-19 among those with established high levels of ACE2 expression strongly support our hypothesis. Considering the burden of COVID-19 infection in these vulnerable groups and the impact of the potential therapeutic and preventive measures that would result from adopting ACE2-driven anti-viral strategies, our hypothesis may expedite global efforts to control the current COVID-19 pandemic.

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FUNCTION AND MECHANISM OF ANGIOTENSIN-CONVERTING ENZYME-2 RECEPTOR TO TRANSPORT SARS-COV-2 INTO THE HOST CELLS―A REVIEW

Journal of Experimental Biology and Agricultural Sciences ◽

10.18006/2020.8(spl-1-sars-cov-2).s190.s201 ◽

2020 ◽

Vol 8 (Spl-1-SARS-CoV-2) ◽

pp. S190-S201

Author(s):

Muhammad Bilal ◽

◽

Muhammad Iqbal Sarfaraz ◽

Muhammad Iqbal Husnain ◽

Nimra Sardar ◽

...

Keyword(s):

Angiotensin Converting Enzyme ◽

Viral Entry ◽

Host Cells ◽

Lung Cells ◽

The Novel ◽

Converting Enzyme ◽

Angiotensin Converting Enzyme 2 ◽

Lung Failure ◽

Novel Coronavirus ◽

Severe Lung

Novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has rapidly spread across the world. SARS-CoV-2 is viewed as a continuous global health threat resulting in an alarming number of fatalities worldwide. Angiotensin-converting enzyme-2 (ACE2) has been recognized as one of the vital receptors for the SARS-CoV-2, leading to viral entry into the host cells. It also helps many other receptors, which initiate the entry of SARS-CoV-2 in the host body. A variety of proteins and enzymes are involved in triggering the transport mechanism. The route of viral infection depends on the distribution and expression of receptors, as the virus reaches the cell by binding to cell receptors to complete intracellular replication, virus release, and cause cytotoxicity. In addition to alveolar lung tissues, ACE2 also plays a pivotal role in other organs. Due to the abundant presence in lung cells, SARS-CoV-2 mostly affects the lungs and causes their destruction. The spike protein utilizes the digestion of ACE2, which strongly contributes to the pathogenesis of severe lung failure. Different experiments show that ACE2 not only helps the virus to migrate in the host cell but also allow us to fight against this pandemic disease. This review article summarizes the current progress that highlights the critical biological functionalities and mechanisms of ACE2 as the novel receptor to transport SARS-CoV-2 into host cells matrix.

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Angiotensin Converting Enzyme-2: A Doorway for SARS-CoV-2

Coronaviruses ◽

10.2174/2666796702666210222110044 ◽

2021 ◽

Vol 02 ◽

Author(s):

Vikas Pandey ◽

Indu Lata Kanwar ◽

Tanweer Haider ◽

Vishal Gour ◽

Monika Vishwakarma ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Angiotensin Converting Enzyme ◽

Human Body ◽

Spike Protein ◽

Specific Method ◽

The Novel ◽

Converting Enzyme ◽

Angiotensin Converting Enzyme 2 ◽

Novel Coronavirus

: The novel coronavirus severe acute respiratory syndrome Corona Virus-2 (SARS-CoV-2) has become a pandemic, as declared by WHO in March 2020 producing the deleterious effects to patients worldwide. The angiotensin-converting enzyme-2 (ACE-2) has been recognized as the co-receptor for SARS-CoV-2 infections and may acts as a therapeutic step in blocking the enzyme to reduce SARS-CoV-2 expression and further cellular entry. Presently, the role of ACE-2 in coronavirus disease 2019 (COVID-19) infection has been known and the experts have started working on the enzyme ACE-2 for the management and treatment of this pandemic disease. The binding of spike (S) protein of SARS-CoV-2 to these receptors is the most important step and plays a key role in viral replication, thus this enzyme is becoming the doorway for the entry and spread in the human body causing asymptomatic pneumonia and severe of which is leading to death. As no specific method to prevent and treat this disease is available, the use of ACE-2 as a targeting ligand with COVID-19 virus spike protein could be helpful in the proper management of SARS-CoV-2 pneumonia.

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Blocking Effect of Demethylzeylasteral on the Interaction between Human ACE2 Protein and SARS-CoV-2 RBD Protein Discovered Using SPR Technology

Molecules ◽

10.3390/molecules26010057 ◽

2020 ◽

Vol 26 (1) ◽

pp. 57

Author(s):

Zhi-Ling Zhu ◽

Xiao-Dan Qiu ◽

Shuo Wu ◽

Yi-Tong Liu ◽

Ting Zhao ◽

...

Keyword(s):

Therapeutic Strategy ◽

Blocking Effect ◽

Spike Protein ◽

Binding Affinities ◽

The Novel ◽

Converting Enzyme ◽

Primary Method ◽

Angiotensin Converting Enzyme 2 ◽

Novel Coronavirus ◽

Effective Drugs

The novel coronavirus disease (2019-nCoV) has been affecting global health since the end of 2019, and there is no sign that the epidemic is abating. Targeting the interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor is a promising therapeutic strategy. In this study, surface plasmon resonance (SPR) was used as the primary method to screen a library of 960 compounds. A compound 02B05 (demethylzeylasteral, CAS number: 107316-88-1) that had high affinities for S-RBD and ACE2 was discovered, and binding affinities (KD, μM) of 02B05-ACE2 and 02B05-S-RBD were 1.736 and 1.039 μM, respectively. The results of a competition experiment showed that 02B05 could effectively block the binding of S-RBD to ACE2 protein. Furthermore, pseudovirus infection assay revealed that 02B05 could inhibit entry of SARS-CoV-2 pseudovirus into 293T cells to a certain extent at nontoxic concentration. The compoundobtained in this study serve as references for the design of drugs which have potential in the treatment of COVID-19 and can thus accelerate the process of developing effective drugs to treat SARS-CoV-2 infections.

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Pathological Role of Angiotensin II in Severe COVID-19

TH Open ◽

10.1055/s-0040-1713678 ◽

2020 ◽

Vol 04 (02) ◽

pp. e138-e144 ◽

Cited By ~ 5

Author(s):

Wolfgang Miesbach

Keyword(s):

Angiotensin Ii ◽

Angiotensin Converting Enzyme ◽

Treatment Options ◽

Renin Angiotensin System ◽

Target Cells ◽

Converting Enzyme ◽

Angiotensin System ◽

Angiotensin Converting Enzyme 2 ◽

Renin Angiotensin ◽

Novel Coronavirus

AbstractThe activated renin–angiotensin system induces a prothrombotic state resulting from the imbalance between coagulation and fibrinolysis. Angiotensin II is the central effector molecule of the activated renin–angiotensin system and is degraded by the angiotensin-converting enzyme 2 to angiotensin (1–7). The novel coronavirus infection (classified as COVID-19) is caused by the new coronavirus SARS-CoV-2 and is characterized by an exaggerated inflammatory response that can lead to severe manifestations such as acute respiratory distress syndrome, sepsis, and death in a proportion of patients, mostly elderly patients with preexisting comorbidities. SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptor to enter the target cells, resulting in activation of the renin–angiotensin system. After downregulating the angiotensin-converting enzyme 2, the vasoconstrictor angiotensin II is increasingly produced and its counterregulating molecules angiotensin (1–7) reduced. Angiotensin II increases thrombin formation and impairs fibrinolysis. Elevated levels were strongly associated with viral load and lung injury in patients with severe COVID-19. Therefore, the complex clinical picture of patients with severe complications of COVID-19 is triggered by the various effects of highly expressed angiotensin II on vasculopathy, coagulopathy, and inflammation. Future treatment options should focus on blocking the thrombogenic and inflammatory properties of angiotensin II in COVID-19 patients.

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DOCKING STUDY OF NOVEL N-SUBSTITUTED 2,5-BIS[(7-CHLOROQUINOLIN-4-YL)AMINO]PENTANOIC DERIVATIVES AS SELECTIVE HIGH-BINDER WITH ANGIOTENSIN CONVERTING ENZYME 2

INDIAN DRUGS ◽

10.53879/id.57.08.12425 ◽

2020 ◽

Vol 57 (08) ◽

pp. 16-24

Author(s):

Mohammed Oday Ezzat ◽

Basma M. Abd Razik ◽

Kutayba F. Dawood

Keyword(s):

Angiotensin Converting Enzyme ◽

Active Site ◽

Docking Study ◽

World Health ◽

Converting Enzyme ◽

Angiotensin Converting Enzyme 2 ◽

Pharmaceutical Properties ◽

Novel Coronavirus

The prevalence of a novel coronavirus (2019-nCoV) in the last few months represents a serious threat as a world health emergency concern. Angiotensin-converting enzyme 2 (ACE2) is the host cellular receptor for the respiratory syndrome of coronavirus epidemic in 2019 (2019-nCoV). In this work, the active site of ACE2 is successfully located by Sitmap prediction tool and validated by different marketed drugs. To design and discover new medical countermeasure drugs, we evaluate a total of 184 molecules of 7-chloro-N-methylquinolin-4-amine derivatives for binding affinity inside the crystal structure of ACE2 located active site. A novel series of N-substituted 2,5-bis[(7-chloroquinolin-4-yl)amino]pentanoic acid derivatives is generated and evaluated for a prospect as a lead compound for (2019-nCoV) medication with a docking score range of (-10.60 to -8.99) kcal/mol for the highest twenty derivatives. Moreover, the ADME pharmaceutical properties were evaluated for further proposed experimental evaluation in vitro or in vivo

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A plausible path to contain the spread of 2019 Novel Coronavirus; a computational analysis prompts to the use of ACE2 receptor blockers

10.21203/rs.3.rs-21838/v1 ◽

2020 ◽

Author(s):

Christopher Whitman

Keyword(s):

Angiotensin Converting Enzyme ◽

World Health ◽

Converting Enzyme ◽

Time Sharing ◽

Angiotensin Converting Enzyme 2 ◽

Bioinformatic Tools ◽

Receptor Blockers ◽

Genetic Sequences ◽

Novel Coronavirus ◽

Health Organization

Abstract Starting December 30th, 2019, a virus spread from Wuhan, in the Hubei Province of China. The virus had soon been recognized as part of the Coronavirus and temporarily named 2019 Novel Coronavirus. The dramatic increase of infections led to the death of over 400 people, by Feb 4th, 2020. By this day the virus had already crossed into 27 countries. March 11th, 2020 the World Health Organization declared the Novel Coronavirus a pandemic, pointing to over 118,000 cases of infections in over 110 countries. This public health threat drove the international community to real-time sharing of the genetic sequences isolated from the viruses. We used these freely accessible genetic data, while leveraging bioinformatic tools, with the intent to explore possible contributions to address this threat. Angiotensin-converting Enzyme 2 Inhibition has been proven to be a valuable strategy address the spread of SARS. After proving remarkable genetic similarities between SARS and the 2019 Novel Coronavirus, we computationally built the first known ex-novo model of the 2019 Novel Coronavirus Spike Glycoprotein entirely generated from its aminoacidic sequence, using I-TASEER. We then assessed the 2019 Novel Coronavirus interaction with the human Angiotensin-converting Enzyme 2. This research prompts at the potential use of Angiotensin- converting Enzyme 2 receptors blockers, as both clinical and prophylaxis measures to contain the spread of 2019 Novel Coronavirus.

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Human genetic basis of coronavirus disease 2019

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00736-8 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Hao Deng ◽

Xue Yan ◽

Lamei Yuan

Keyword(s):

Angiotensin Converting Enzyme ◽

Genetic Basis ◽

Human Leukocyte ◽

Converting Enzyme ◽

Angiotensin Converting Enzyme 2 ◽

Leukocyte Antigen ◽

Host Genetic ◽

Considerable Morbidity ◽

Novel Coronavirus ◽

Hla Genotype

AbstractCoronavirus disease 2019 (COVID-19) caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in considerable morbidity and mortality worldwide. COVID-19 incidence, severity, and mortality rates differ greatly between populations, genders, ABO blood groups, human leukocyte antigen (HLA) genotypes, ethnic groups, and geographic backgrounds. This highly heterogeneous SARS-CoV-2 infection is multifactorial. Host genetic factors such as variants in the angiotensin-converting enzyme gene (ACE), the angiotensin-converting enzyme 2 gene (ACE2), the transmembrane protease serine 2 gene (TMPRSS2), along with HLA genotype, and ABO blood group help to explain individual susceptibility, severity, and outcomes of COVID-19. This review is focused on COVID-19 clinical and viral characteristics, pathogenesis, and genetic findings, with particular attention on genetic diversity and variants. The human genetic basis could provide scientific bases for disease prediction and targeted therapy to address the COVID-19 scourge.

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Angiotensin-Converting Enzyme 2 (ACE2) in the Pathogenesis of ARDS in COVID-19

Frontiers in Immunology ◽

10.3389/fimmu.2021.732690 ◽

2021 ◽

Vol 12 ◽

Author(s):

Keiji Kuba ◽

Tomokazu Yamaguchi ◽

Josef M. Penninger

Keyword(s):

Angiotensin Converting Enzyme ◽

Neutralizing Antibodies ◽

Cell Entry ◽

Converting Enzyme ◽

Sars Coronavirus ◽

Angiotensin Converting Enzyme 2 ◽

Infected People ◽

Critical Attention ◽

Novel Coronavirus

Seventeen years after the epidemic of SARS coronavirus, a novel coronavirus SARS-CoV-2-emerged resulting in an unprecedented pandemic. Angiotensin-converting enzyme 2 (ACE2) is an essential receptor for cell entry of SARS-CoV-2 as well as the SARS coronavirus. Despite many similarities to SARS coronavirus, SARS-CoV-2 exhibits a higher affinity to ACE2 and shows higher infectivity and transmissibility, resulting in explosive increase of infected people and COVID-19 patients. Emergence of the variants harboring mutations in the receptor-binding domain of the Spike protein has drawn critical attention to the interaction between ACE2 and Spike and the efficacies of vaccines and neutralizing antibodies. ACE2 is a carboxypeptidase which degrades angiotensin II, B1-bradykinin, or apelin, and thereby is a critical regulator of cardiovascular physiology and pathology. In addition, the enzymatic activity of ACE2 is protective against acute respiratory distress syndrome (ARDS) caused by viral and non-viral pneumonias, aspiration, or sepsis. Upon infection, both SARS-CoV-2 and SARS coronaviruses downregulates ACE2 expression, likely associated with the pathogenesis of ARDS. Thus, ACE2 is not only the SARS-CoV-2 receptor but might also play an important role in multiple aspects of COVID-19 pathogenesis and possibly post-COVID-19 syndromes. Soluble forms of recombinant ACE2 are currently utilized as a pan-variant decoy to neutralize SARS-CoV-2 and a supplementation of ACE2 carboxypeptidase activity. Here, we review the role of ACE2 in the pathology of ARDS in COVID-19 and the potential application of recombinant ACE2 protein for treating COVID-19.

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