scholarly journals The potential role of Bromhexine in the management of COVID-19: Decipher and a real game-changer

2021 ◽  
Vol 5 (01) ◽  
pp. 1-4
Author(s):  
Hayder M. Al-Kuraishy ◽  
Marwa S. Al-Niemi ◽  
Nawar R. Hussain ◽  
Ali I. Al-Gareeb ◽  
Claire Lugnier
Keyword(s):  
Potential Role ◽  
Host Cells ◽  
Bronchial Epithelial ◽  
S Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Novel Coronavirus ◽  
Transmembrane Serine Protease ◽  
Game Changer

Primary infection of SARS-CoV-2 (novel coronavirus or 2019-nCoV), which leads to Covid-19, targets specific cells, such as nasal, bronchial epithelial and pneumocytes, through the viral structural spike (S) protein that binds to the angiotensin-converting enzyme 2 (ACE2) receptor. Also, type 2 transmembrane serine protease (TMPRSS2) present in the host cell promotes viral uptake by cleaving ACE2 and triggering the SARS-CoV-2 S protein, which facilitates SARS-CoV-2 entry into host cells. One of the TMPRSS2 inhibitors with a greater distribution capacity into the lung tissue is bromhexine hydrochloride which attenuates the entry and proliferation of SARS-CoV-2. Bromhexine is an effective drug in the management and treatment of Covid-19 pneumonia via targeting ACE2/ TMPRSS2 pathway. However, prospective and controlled clinical trials are recommended to confirm this observation.

COVID 19: Camostat and The Role of Serine Protease Entry Inhibitor TMPRSS2

2020 ◽  
Author(s):  
Stefan Bittmann
Keyword(s):  
Host Cell ◽  
Serine Protease ◽  
Cellular Protein ◽  
Host Cells ◽  
The Novel ◽  
Robert Koch Institute ◽  
Angiotensin Converting Enzyme 2 ◽  
Novel Coronavirus ◽  
Transmembrane Serine Protease

According to the latest research, the novel coronavirus uses the protein angiotensin-converting enzyme 2 (ACE-2) as a receptor for docking to the host cell. Essential for entry is the priming of the spike (S) protein of the virus by host cell proteases. A broadly based team led by infection biologists from the German Primate Centre and with the participation of the Charité Hospital in Berlin, the Hanover Veterinary University Foundation, the BG-UnfallklinikMurnau, the LMU Munich, the Robert Koch Institute and the German Centre for Infection Research wanted to find out how SARS-CoV-2 enters host cells and how this process can be blocked [1]. They have published their findings in the journal "Cell" [1]. The team of scientists was initially able to confirm that SARS-CoV-2 docks to the host cell via the ACE-2 receptor. They also identified Transmembrane serine protease 2 (TMPRSS2) as the cellular protein responsible for entry into the cell [1-3].

scholarly journals Investigation of the genetic variation in ACE2 on the structural recognition by the novel coronavirus (SARS-CoV-2)

2020 ◽  
Author(s):  
Xingyi Guo ◽  
Zhishan Chen ◽  
Yumin Xia ◽  
Weiqiang Lin ◽  
Hongzhi Li
Keyword(s):  
Genetic Variation ◽  
The Novel ◽  
S Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Missense Variants ◽  
Catalytic Metal ◽  
Using Data ◽  
Novel Coronavirus ◽  
Insight Into

Abstract Background: The outbreak of coronavirus disease (COVID-19) was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), through its surface spike glycoprotein (S-protein) recognition on the receptor Angiotensin-converting enzyme 2 (ACE2) in humans. However, it remains unclear how genetic variations in ACE2 may affect its function and structure, and consequently alter the recognition by SARS-CoV-2. Methods: We have systemically characterized missense variants in the gene ACE2 using data from the Genome Aggregation Database (gnomAD; N = 141,456). To investigate the putative deleterious role of missense variants, six existing functional prediction tools were applied to evaluate their impact. We further analyzed the structural flexibility of ACE2 and its protein-protein interface with the S-protein of SARS-CoV-2 using our developed Legion Interfaces Analysis (LiAn) program.Results: Here, we characterized a total of 12 ACE2 putative deleterious missense variants. Of those 12 variants, we further showed that p.His378Arg could directly weaken the binding of catalytic metal atom to decrease ACE2 activity and p.Ser19Pro could distort the most important helix to the S-protein. Another seven missense variants may affect secondary structures (i.e. p.Gly211Arg; p.Asp206Gly; p.Arg219Cys; p.Arg219His, p.Lys341Arg, p.Ile468Val, and p.Ser547Cys), whereas p.Ile468Val with AF = 0.01 is only present in Asian.Conclusions: We provide strong evidence of putative deleterious missense variants in ACE2 that are present in specific populations, which could disrupt the function and structure of ACE2. These findings provide novel insight into the genetic variation in ACE2 which may affect the SARS-CoV-2 recognition and infection, and COVID-19 susceptibility and treatment.

scholarly journals Is There a Link between Bisphenol A (BPA), a Key Endocrine Disruptor, and the Risk for SARS-CoV-2 Infection and Severe COVID-19?

2020 ◽  
Vol 9 (10) ◽  
pp. 3296
Author(s):  
Aeman Zahra ◽  
Cristina Sisu ◽  
Elisabete Silva ◽  
Sophie-Christine De Aguiar Greca ◽  
Harpal S. Randeva ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Potential Role ◽  
Metabolic Diseases ◽  
Endocrine Disrupting Chemicals ◽  
Angiotensin Converting Enzyme 2 ◽  
Endocrine Disrupting ◽  
Membrane Bound ◽  
Transmembrane Serine Protease ◽  
G Protein Coupled

Infection by the severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) is the causative agent of a new disease (COVID-19). The risk of severe COVID-19 is increased by certain underlying comorbidities, including asthma, cancer, cardiovascular disease, hypertension, diabetes, and obesity. Notably, exposure to hormonally active chemicals called endocrine-disrupting chemicals (EDCs) can promote such cardio-metabolic diseases, endocrine-related cancers, and immune system dysregulation and thus, may also be linked to higher risk of severe COVID-19. Bisphenol A (BPA) is among the most common EDCs and exerts its effects via receptors which are widely distributed in human tissues, including nuclear oestrogen receptors (ERα and ERβ), membrane-bound oestrogen receptor (G protein-coupled receptor 30; GPR30), and human nuclear receptor oestrogen-related receptor gamma. As such, this paper focuses on the potential role of BPA in promoting comorbidities associated with severe COVID-19, as well as on potential BPA-induced effects on key SARS-CoV-2 infection mediators, such as angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Interestingly, GPR30 appears to exhibit greater co-localisation with TMPRSS2 in key tissues like lung and prostate, suggesting that BPA exposure may impact on the local expression of these SARS-CoV-2 infection mediators. Overall, the potential role of BPA on the risk and severity of COVID-19 merits further investigation.

SARS-CoV-2 Entry inhibitors targeting virus-ACE2 or virus-TMPRSS2 interactions

2021 ◽  
Vol 28 ◽  
Author(s):  
Hao Lin ◽  
Srinivasulu Cherukupalli ◽  
Da Feng ◽  
Shenghua Gao ◽  
Dongwei Kang ◽  
...  
Keyword(s):  
Life Cycle ◽  
Host Cells ◽  
Cell Surface Receptor ◽  
Target Cells ◽  
S Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Entry Inhibitors ◽  
Concise Report ◽  
Surface Receptor ◽  
Transmembrane Serine Protease

: COVID-19 is an infectious disease caused by SARS-CoV-2. The life cycle of SARS-CoV-2 includes the entry into the target cells, replicase translation, replicating and transcribing genomes, translating structural proteins, assembling and releasing new virions. Entering host cells is a crucial stage in the early life cycle of the virus, and blocking this stage can effectively prevent virus infection. SARS enters the target cells mediated by the interaction between the viral S protein and the target cell surface receptor angiotensin-converting enzyme 2 (ACE2), as well as the cleavage effect of type-II transmembrane serine protease (TMPRSS2) on the S protein. Therefore, the ACE2 receptor and TMPRSS2 are important targets for SARS-CoV-2 entry inhibitors. Herein, we provide a concise report/information on drugs with potential therapeutic value targeting virus-ACE2 or virus-TMPRSS2 interactions, to provide a reference for the design and discovery of potential entry inhibitors against SARS-CoV-2.

scholarly journals Potential Role of Antioxidant and Anti-Inflammatory Therapies to Prevent Severe SARS-Cov-2 Complications

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 272
Author(s):  
Anna M. Fratta Pasini ◽  
Chiara Stranieri ◽  
Luciano Cominacini ◽  
Chiara Mozzini
Keyword(s):  
Potential Role ◽  
Viral Infections ◽  
Host Cells ◽  
Nuclear Factor ◽  
Angiotensin Converting Enzyme 2 ◽  
Pyrin Domain ◽  
Nrf2 Activation ◽  
Anti Inflammatory ◽  
Receptor Family

The coronavirus disease 2019 (COVID-19) pandemic is caused by a novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2). Here, we review the molecular pathogenesis of SARS-CoV-2 and its relationship with oxidative stress (OS) and inflammation. Furthermore, we analyze the potential role of antioxidant and anti-inflammatory therapies to prevent severe complications. OS has a potential key role in the COVID-19 pathogenesis by triggering the NOD-like receptor family pyrin domain containing 3 inflammasome and nuclear factor-kB (NF-kB). While exposure to many pro-oxidants usually induces nuclear factor erythroid 2 p45-related factor2 (NRF2) activation and upregulation of antioxidant related elements expression, respiratory viral infections often inhibit NRF2 and/or activate NF-kB pathways, resulting in inflammation and oxidative injury. Hence, the use of radical scavengers like N-acetylcysteine and vitamin C, as well as of steroids and inflammasome inhibitors, has been proposed. The NRF2 pathway has been shown to be suppressed in severe SARS-CoV-2 patients. Pharmacological NRF2 inducers have been reported to inhibit SARS-CoV-2 replication, the inflammatory response, and transmembrane protease serine 2 activation, which for the entry of SARS-CoV-2 into the host cells through the angiotensin converting enzyme 2 receptor. Thus, NRF2 activation may represent a potential path out of the woods in COVID-19 pandemic.

Progress in Studies on Structural and Remedial Aspects of Newly Born Coronavirus, SARS-CoV-2

2020 ◽  
Vol 20 (26) ◽  
pp. 2362-2378
Author(s):  
Satya P. Gupta
Keyword(s):  
Vaccine Development ◽  
Cell Receptor ◽  
Receptor Binding Domain ◽  
S Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
N Protein ◽  
Host Cell Receptor ◽  
The Status ◽  
Novel Coronavirus

The article highlights an up-to-date progress in studies on structural and the remedial aspects of novel coronavirus 2019-nCoV, renamed as SARS-CoV-2, leading to the disease COVID-19, a pandemic. In general, all CoVs including SARS-CoV-2 are spherical positive single-stranded RNA viruses containing spike (S) protein, envelope (E) protein, nucleocapsid (N) protein, and membrane (M) protein, where S protein has a Receptor-binding Domain (RBD) that mediates the binding to host cell receptor, Angiotensin Converting Enzyme 2 (ACE2). The article details the repurposing of some drugs to be tried for COVID-19 and presents the status of vaccine development so far. Besides drugs and vaccines, the role of Convalescent Plasma (CP) therapy to treat COVID-19 is also discussed.

scholarly journals Investigation of the genetic variation in ACE2 on the structural recognition by the novel coronavirus (SARS-CoV-2)

2020 ◽  
Author(s):  
Xingyi Guo ◽  
Zhishan Chen ◽  
Yumin Xia ◽  
Weiqiang Lin ◽  
Hongzhi Li
Keyword(s):  
Genetic Variation ◽  
The Novel ◽  
S Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Missense Variants ◽  
Catalytic Metal ◽  
Using Data ◽  
Novel Coronavirus ◽  
Insight Into

Abstract Background: The outbreak of coronavirus disease (COVID-19) was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), through its surface spike glycoprotein (S protein) recognition on the receptor Angiotensin-converting enzyme 2 (ACE2) in humans. However, it remains unclear how genetic variations in ACE2 may affect its function and structure, and consequently alter the recognition by SARS-CoV-2. Methods: We have systemically characterized missense variants in the gene ACE2 using data from the Genome Aggregation Database (gnomAD; N = 141,456). To investigate the putative deleterious role of missense variants, six existing functional prediction tools were applied to evaluate their impact. We further analyzed structural flexibility of ACE2 and the protein-protein interface with the S protein of SARS-CoV-2 using our developed Legion Interfaces Analysis (LiAn) program. Results: Here, we characterized a total of 12 ACE2 putative deleterious missense variants. Of those 12 variants, we further showed that p.His378Arg could directly weaken the binding of catalytic metal atom to decrease ACE2 activity and p.Ser19Pro could distort the most important helix to the S-protein. Another seven missense variants may affect secondary structures (i.e. p.Gly211Arg; p.Asp206Gly; p.Arg219Cys; p.Arg219His, p.Lys341Arg, p.Ile468Val, and p.Ser547Cys), whereas p.Ile468Val with AF = 0.01 is only present in Asian. Conclusions: We provide strong evidence of putative deleterious missense variants in ACE2 that are present in specific populations, which could disrupt the function and structure of ACE2. These findings provide novel insight into the genetic variation in ACE2 which may affect the SARS-CoV-2 recognition and infection, and COVID-19 susceptibility and treatment.

scholarly journals Potential role of Curcumin against viral infections with a view on structure and pathogenesis of COVID-19

2020 ◽  
Author(s):  
Kajal Singh
Keyword(s):  
Treatment Option ◽  
Viral Entry ◽  
Potential Role ◽  
Viral Infections ◽  
Host Cells ◽  
Health Crisis ◽  
Positive Sense ◽  
Anti Oxidant ◽  
Novel Coronavirus

A novel Coronavirus disease 2019 (nCOVID-19) is an enveloped, positive sense, single stranded RNA viruses of zoonotic origin caused by Severe acute respiratory syndrome coronavirus, currently responsible for pandemic health crisis. Due to increasing mortality rate there is an immediate need to develop possible treatments and understand the mechanism through which virus can cause complications in human body. The review intended to provide link between natural product as treatment and COVID-19 disease. Therefore, this review summarizes the structure, pathogenesis as well as understanding the various role of curcumin as a treatment option for COVID-19 which includes: targeting viral entry to host cells, targeting viral replication, anti-viral, anti-inflammatory and anti-oxidant. Hence, curcumin can be a potential treatment option for COVID-19 patients and this review also suggest that more clinical research and development is needed in order to prepare a new drug for emerging SARS-CoV-2.

scholarly journals Human ACE2 receptor polymorphisms and altered susceptibility to SARS-CoV-2

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Kushal Suryamohan ◽  
Devan Diwanji ◽  
Eric W. Stawiski ◽  
Ravi Gupta ◽  
Shane Miersch ◽  
...  
Keyword(s):  
Structural Data ◽  
Respiratory Illness ◽  
Host Cells ◽  
Host Susceptibility ◽  
Pseudotyped Virus ◽  
S Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Host Interaction ◽  
Biochemical Assays ◽  
Novel Coronavirus

AbstractCOVID-19 is a respiratory illness caused by a novel coronavirus called SARS-CoV-2. The viral spike (S) protein engages the human angiotensin-converting enzyme 2 (ACE2) receptor to invade host cells with ~10–15-fold higher affinity compared to SARS-CoV S-protein, making it highly infectious. Here, we assessed if ACE2 polymorphisms can alter host susceptibility to SARS-CoV-2 by affecting this interaction. We analyzed over 290,000 samples representing >400 population groups from public genomic datasets and identified multiple ACE2 protein-altering variants. Using reported structural data, we identified natural ACE2 variants that could potentially affect virus–host interaction and thereby alter host susceptibility. These include variants S19P, I21V, E23K, K26R, T27A, N64K, T92I, Q102P and H378R that were predicted to increase susceptibility, while variants K31R, N33I, H34R, E35K, E37K, D38V, Y50F, N51S, M62V, K68E, F72V, Y83H, G326E, G352V, D355N, Q388L and D509Y were predicted to be protective variants that show decreased binding to S-protein. Using biochemical assays, we confirmed that K31R and E37K had decreased affinity, and K26R and T92I variants showed increased affinity for S-protein when compared to wildtype ACE2. Consistent with this, soluble ACE2 K26R and T92I were more effective in blocking entry of S-protein pseudotyped virus suggesting that ACE2 variants can modulate susceptibility to SARS-CoV-2.

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