Repurposing Nimesulide, a Potent Inhibitor of the B0AT1 Subunit of the SARS-CoV-2 Receptor, as a Therapeutic Adjuvant of COVID-19

2020 ◽  
Vol 25 (10) ◽  
pp. 1171-1173 ◽  
Author(s):  
Mariafrancesca Scalise ◽  
Cesare Indiveri

The global pandemic caused by the SARS-CoV-2 infection is a health emergency that needs to be addressed immediately. The international scientific community, following World Health Organization (WHO) indications, launched different trials for testing drugs putatively able to block the SARS-CoV-2 infection or treat the COVID-19 disease symptoms. In parallel, studies devoted to a better understanding of SARS-CoV-2 biology are in the course for designing an effective vaccine. One of the human membrane proteins known to be docked by the virus is angiotensin-converting enzyme 2 (ACE2), proposed to be responsible for viral entry in target cells. Recently, the 3D structure of ACE2 has been obtained, showing its physical interaction with B0AT1 (SLC6A19), a plasma membrane transporter involved in the trafficking of amino acids in cells. The receptor targeted by SARS-CoV-2 is a supercomplex formed by a dimer of ACE2-B0AT1, in which ACE2 binds the viral protein and B0AT1 stabilizes the heterodimer. As a serendipity occurrence, nimesulide was shown to abolish the transport function of B0AT1. Here we suggest including nimesulide in the list of drugs to be tested for the identification of co-adjuvants in the treatment of COVID-19.

2020 ◽  
Vol 27 (2) ◽  
pp. 10-17
Author(s):  
V. M. Kovalenko ◽  
E. G. Nesukay ◽  
T. M. Kornienko ◽  
N. S. Titova

The World Health Organization announced on March 11, 2020 that coronavirus disease 2019 (COVID-19) is a global pandemic. The data of studies confirming that cardiovascular diseases are a common concomitant pathology among patients with COVID-19 and cardiological patients have a more severe course and high mortality are presented. The mechanism of interaction between COVID-19 and cardiovascular diseases has been identified. First, angiotensin-converting enzyme-2 (ACE2), a key enzyme in the renin-angiotensin-aldosterone system, is recognized as a functional receptor for SARS-CoV-2. Secondly, it was proved that SARS-CoV-2 through the cytokine mechanism causes direct damage to the myocardium and can disrupt the function of the cardiovascular system. This review highlights the need for continued use of ACE inhibitors and angiotensin receptor blockers in the treatment of patients with arterial hypertension, coronary heart disease and heart failure, as well as recommendations for urgent and emergency care for cardiac patients in the context of the COVID-19 pandemic.


2021 ◽  
Vol 8 (4) ◽  
pp. 777
Author(s):  
Arundhathi Shankaralingappa ◽  
Arun Babu Thirunavukkarasu

World health organization declared COVID-19 caused by SARS CoV-2 virus as a pandemic in early 2020. The target cells facilitating viral entry are ACE-2 receptor bearing cells like bronchial epithelial cells and pneumocytes.  Children pose a less risk compared to adults in acquiring this disease and mortality in them is low due to protective pathogenesis. Children with COVID-19 are also at risk of developing unique immunological phenomena, known as multi-system inflammatory syndrome in children. MIS-C is considered to be hyperimmune state resulting from cytokine storm and circulating immune complexes. This mini-review reflects the most recent understanding of the pathogenesis in children with special emphasis on MIS-C.


Author(s):  
Jenny Mendis ◽  
Ekrem Kaya ◽  
Tugba G. Kucukkal

Coronaviruses are a large family of viruses that can cause respiratory infections with varying severity from common cold to severe diseases such as novel coronavirus disease (COVID-19). COVID-19 has been declared as a global pandemic by the World Health Organization on March 11, 2020 and with the development of vaccines it slowed down as of this date. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses its spike glycoprotein (Sgp) to bind human angiotensin-converting enzyme 2 (hACE2) receptor, and mediates membrane fusion and virus entry. The recognition of Sgp to human ACE2 and its high affinity for it has been of great importance since this provides the first step in viral entry to human cells. Therefore, it is crucial to identify key residues (hotspots) in this process. In this study, computational alanine scanning has been performed for Sgp and hACE2. The residues identified with significance in binding and other residues in close proximity were studied further through molecular mechanics-based protein binding free energy change prediction methods. Moreover, the interfacial residues in both proteins were investigated for their cooperative binding. Additionally, folding free energy changes upon mutation to Ala were calculated to assess their effect on stability of Sgp and hACE2. Our results taken together with findings from previous studies revealed the residues that are most significant and are relatively significant in binding of Sgp to human ACE2 protein.


2020 ◽  
Vol 11 (SPL1) ◽  
pp. 748-752
Author(s):  
Swapnali Khabade ◽  
Bharat Rathi ◽  
Renu Rathi

A novel, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causes severe acute respiratory syndrome and spread globally from Wuhan, China. In March 2020 the World Health Organization declared the SARS-Cov-2 virus as a COVID- 19, a global pandemic. This pandemic happened to be followed by some restrictions, and specially lockdown playing the leading role for the people to get disassociated with their personal and social schedules. And now the food is the most necessary thing to take care of. It seems the new challenge for the individual is self-isolation to maintain themselves on the health basis and fight against the pandemic situation by boosting their immunity. Food organised by proper diet may maintain the physical and mental health of the individual. Ayurveda aims to promote and preserve the health, strength and the longevity of the healthy person and to cure the disease by properly channelling with and without Ahara. In Ayurveda, diet (Ahara) is considered as one of the critical pillars of life, and Langhana plays an important role too. This article will review the relevance of dietetic approach described in Ayurveda with and without food (Asthavidhi visheshaytana & Lanhgan) during COVID-19 like a pandemic.


2020 ◽  
Vol 11 (SPL1) ◽  
pp. 758-762
Author(s):  
Amit Biswas ◽  
KunalChandankhede

Wuhan originated Covid-19 disease is caused by SARC-COV 2 virus. It is a contagious disease it spread all over the world. World health organization declared a global pandemic disease. In Covid-19 immunity plays an important role. In old age people or having other co-morbid conditions the mortality rate is more. Ayurveda has a big role in improved immunity or to intact immunity. The principle of Ayurveda is to keep individual swastha (diseases free). To maintain individual disease-free Ritucharya is one of the important subjects of Ayurveda. Aimed of study is to find out Ritucharya literature from the Ayurveda and modern research specifically Varsha and Sharad ritu. Ritucharya contains dietary regimen, living modification, common medicine, and contraindicated things those changing according to environmental change. Upcoming season in India is Varsha and Sharad ritu. Environmental changes are huge in this season and it directly affected human beings. So this study reveals property of ritu, dietary regimen, living modification, common medicine and contraindicated things in upcoming varsha and sharad ritu.


2020 ◽  
Vol 17 ◽  
Author(s):  
Ajoy Basak ◽  
Sarmistha Basak

: The current global pandemic outbreak of a novel type of corona virus termed by World Health Organization as COVID-19 became an grave concern and worry to human health and world economy. Intense research efforts are now underway worldwide to combat and prevent the spread of this deadly disease. This zoonotic virus, a native to bat population is most likely transmitted to human via a host reservoir. Due to its close similarity to previously known SARS CoV (Severe Acute Respiratory Syndrome Corona Virus) of 2002 and related MERS CoV (Middle East Respiratory Syndrome Corona Virus) of 2012, it is also known as SARS CoV2. But unlike them it is far too infectious, virulent and lethal. Among its various proteins, the surface spike glycoprotein “S” has drawn significant attention because of its implication in viral recognition and host-virus fusion process. A detail comparative analysis of “S” proteins of SARS CoV (now called SARS CoV1), SARS CoV2 (COVID-19) and MERS CoV based on structure, sequence alignment, host cleavage sites, receptor binding domains, potential glycosylation and Cys-disulphide bridge locations has been performed. It revealed some key features and variations that may elucidate the high infection and virulence character of COVID-19. Moreover this crucial information may become useful in our quest for COVID-19 therapeutics and vaccines.


Coronaviruses ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 49-56
Author(s):  
Gaurav M. Doshi ◽  
Hemen S. Ved ◽  
Ami P. Thakkar

The World Health Organization (WHO) has recently announced the spread of novel coronavirus (nCoV) globally and has declared it a pandemic. The probable source of transmission of the virus, which is from animal to human and human to human contact, has been established. As per the statistics reported by the WHO on 11th April 2020, data has shown that more than sixteen lakh confirmed cases have been identified globally. The reported cases related to nCoV in India have been rising substantially. The review article discusses the characteristics of nCoV in detail with the probability of potentially effective old drugs that may inhibit the virus. The research may further emphasize and draw the attention of the world towards the development of an effective vaccine as well as alternative therapies. Moreover, the article will help to bridge the gap between the new researchers since it’s the current thrust area of research.


Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Vikram Rao ◽  
Subrat Kumar Bhattamisra

Background: COVID-19, a Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2) was first diagnosed in the patients from Wuhan, China in December 2019. Within couple of months of infection, it was declared as pandemic by World health organization. COVID-19 has become the most contagious infection with a serious threat to global health. In this review, we aimed to discuss the pathogenesis, diagnostics, current treatments and potential vaccines for COVID-19. Methods: An extensive literature search was conducted using keywords “COVID-19”; “Coronavirus”; “SARS-Cov-2”; “SARS” in public domains of Google, Google scholar, PubMed, and ScienceDirect. Selected articles were used to construct this review. Results: SARS-Cov-2 uses the Spike (S) protein on its surface to recognize the receptor on angiotensin-converting enzyme 2 (ACE2) and bind with 10-folds greater affinity than SARS-Cov-1. Molecular assays and immunoassays are the most frequently used tests whereas computed tomography (CT) scans, Artificial intelligence enabled diagnostic tools were also used in patients. In therapeutic treatment, few drugs were repurposed and there are 23 therapeutic molecules including the repurposed drugs are in different stages of clinical trial. Similarly, development of vaccines is also in the pipeline. Few countries have managed well to contain the spread by rapid testing and identifying the clusters. Conclusion: Till now, the acute complications and mortality of COVID-19 has been linked to the pre-existing comorbid conditions or age. Besides the development of therapeutic strategies that includes drugs and vaccine, the long term implication of COVID-19 infection in terms of the disorder/disability in the cured/discharged patients is a new area to investigate.


2021 ◽  
Vol 22 (8) ◽  
pp. 4081
Author(s):  
Ghaydaa A. Shehata ◽  
Kevin C. Lord ◽  
Michaela C. Grudzinski ◽  
Mohamed Elsayed ◽  
Ramy Abdelnaby ◽  
...  

COVID-19 is a severe respiratory disease caused by the newly identified human coronavirus (HCoV) Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The virus was discovered in December 2019, and in March 2020, the disease was declared a global pandemic by the World Health Organization (WHO) due to a high number of cases. Although SARS-CoV-2 primarily affects the respiratory system, several studies have reported neurological complications in COVID-19 patients. Headache, dizziness, loss of taste and smell, encephalitis, encephalopathy, and cerebrovascular diseases are the most common neurological complications that are associated with COVID-19. In addition, seizures, neuromuscular junctions’ disorders, and Guillain–Barré syndrome were reported as complications of COVID-19, as well as neurodegenerative and demyelinating disorders. However, the management of these conditions remains a challenge. In this review, we discuss the prevalence, pathogenesis, and mechanisms of these neurological sequelae that are secondary to SARS-CoV-2 infection. We aim to update neurologists and healthcare workers on the possible neurological complications associated with COVID-19 and the management of these disease conditions.


Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1145
Author(s):  
Hakimeh Baghaei Daemi ◽  
Muhammad Fakhar-e-Alam Kulyar ◽  
Xinlin He ◽  
Chengfei Li ◽  
Morteza Karimpour ◽  
...  

Influenza is a highly known contagious viral infection that has been responsible for the death of many people in history with pandemics. These pandemics have been occurring every 10 to 30 years in the last century. The most recent global pandemic prior to COVID-19 was the 2009 influenza A (H1N1) pandemic. A decade ago, the H1N1 virus caused 12,500 deaths in just 19 months globally. Now, again, the world has been challenged with another pandemic. Since December 2019, the first case of a novel coronavirus (COVID-19) infection was detected in Wuhan. This infection has risen rapidly throughout the world; even the World Health Organization (WHO) announced COVID-19 as a worldwide emergency to ensure human health and public safety. This review article aims to discuss important issues relating to COVID-19, including clinical, epidemiological, and pathological features of COVID-19 and recent progress in diagnosis and treatment approaches for the COVID-19 infection. We also highlight key similarities and differences between COVID-19 and influenza A to ensure the theoretical and practical details of COVID-19.


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