scholarly journals Withaferin A: a potential therapeutic agent against COVID-19 infection

2020 ◽  
Author(s):  
Alex R. Straughn ◽  
Sham S. Kakar

Abstract The outbreak and continued spread of the novel coronavirus disease 2019 (COVID-19) is a preeminent global health threat that has resulted in the infection of over 6 million people worldwide. In addition, the pandemic has claimed the lives of over 350,000 people worldwide. Age and the presence of underlying comorbid conditions have been found to be key determinants of patient mortality. One such comorbidity is the presence of an oncological malignancy, with cancer patients exhibiting an approximate two-fold increase in mortality rate. Due to a lack of data, no consensus has been reached about the best practices for the diagnosis and treatment of cancer patients. Interestingly, two independent research groups have discovered that Withaferin A (WFA), a steroidal lactone with anti-inflammatory and anti-tumorigenic properties, may bind to the viral spike (S-) protein of SARS-CoV-2. Further, preliminary data from our research group has demonstrated that WFA does not alter expression of ACE2 in the lungs of tumor-bearing female mice. Downregulation of ACE2 has recently been demonstrated to increase the severity of COVID-19. Therefore, WFA demonstrates real potential as a therapeutic agent to treat or prevent the spread of COVID-19 due to the reported interference in viral S-protein to host receptor binding and its lack of effect on ACE2 expression in the lungs.

2020 ◽  
Author(s):  
Xingyi Guo ◽  
Zhishan Chen ◽  
Yumin Xia ◽  
Weiqiang Lin ◽  
Hongzhi Li

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.


2020 ◽  
pp. 036354652097518
Author(s):  
Mary K. Mulcahey ◽  
Arianna L. Gianakos ◽  
Angela Mercurio ◽  
Scott Rodeo ◽  
Karen M. Sutton

The outbreak of the novel coronavirus (COVID-19) has resulted in upward of 14 million confirmed cases and >597,000 deaths worldwide as of July 19, 2020. The current disruption in sports activities caused by COVID-19 presents a challenge to physicians, coaches, and trainers in discerning best practices for a safe return to sport. There is a distinct need to develop and adopt consistent measures for resumption of sports activities, including training and competition, in a way that places the health and well-being of athletes at the forefront while also protecting coaches, allied staff, and spectators. This article provides an overview of the effects of COVID-19 in the athletic population and presents considerations for training during the pandemic, as well as guidelines for return to sports as restrictions are lifted.


2020 ◽  
Author(s):  
Zarrin Basharat ◽  
Muhammad Jahanzaib ◽  
Noor Rahman ◽  
Ishtiaq Ahmad Khan ◽  
Azra Yasmin

Abstract Recent infections caused by the novel coronavirus (SARS-CoV-2) have led to global panic and mortality. Here, we analyzed the spike (S) protein of this virus using bioinformatics tools. We aimed to determine relative changes among different coronavirus species over the past two decades and to understand the conservation of the S-protein. Representative sequences of coronaviruses were collected from humans and other animals between 2000 and 2020. Evolutionary analyses found that the S-protein did not evolve overnight, but rather continuously over time. Post-translational modification (PTM) analysis using online tools and virtual screening of S-protein against a phytochemical database of Ayurvedic medicinal compounds (n = 2103) identified the S-protein inhibitors. Among these, top ranked were Gingerol (IUPAC name: 4'-Me ether, 3,5-di-Ac 3,5-di-Gingerdiols), 1-(5-Butyltetrahydro-2-furanyl)-2-hexacosanone and Ginsenoyne N ginseng that stimulates Caspase-3, Caspase-8, and the immune system. Gingerol is found in the fresh ginger and has reputation of being a potent antiviral. These compounds might prove useful to design drugs against COVID-19.


2020 ◽  
Author(s):  
Josh Sumner ◽  
Leah Haynes ◽  
Sarah Nathan ◽  
Cynthia Hudson-Vitale ◽  
Leslie D. McIntosh

AbstractThe novel coronavirus, COVID-19, has sparked an outflow of scientific research seeking to understand the virus, its spread, and best practices in prevention and treatment. If this international research effort is going to be as swift and effective as possible, it will need to rely on a principle of open science. When researchers share data, code, and software and generally make their work as transparent as possible, it allows other researchers to verify and expand upon their work. Furthermore, it allows public officials to make informed decisions. In this study, we analyzed 535 preprint articles related to COVID-19 for eight transparency criteria and recorded study location and funding information. We found that individual researchers have lined up to help during this crisis, quickly tackling important public health questions, often without funding or support from outside organizations. However, most authors could improve their data sharing and scientific reporting practices. The contrast between researchers’ commitment to doing important research and their reporting practices reveals underlying weaknesses in the research community’s reporting habits, but not necessarily their science.


Chemotherapy ◽  
2020 ◽  
pp. 1-6
Author(s):  
Naziye Ak ◽  
Sezai Vatansever

<b><i>Background:</i></b> The novel coronavirus disease 2019 has become a worldwide threat. We aimed to explore reflections of these unexpected changes to newly diagnosed cancer patients. <b><i>Method:</i></b> We searched the 2 months after the index case of our country. The first admission day and the first day of intravenous treatment of newly diagnosed patients were recorded. <b><i>Results:</i></b> In the 60 days measured during the pandemic, the total number of patients on polyclinics was 159/weekdays, and the total applied chemotherapy cycles were 276/week. For comparison, the total numbers in the previous year were 267/weekday and 363/week for polyclinic and applied chemotherapy cycles, respectively. The total number of newly admitted patients in 2020 was 283. For comparison, the number of new patients in the same 60-day period in 2019 was 495. Patients who were admitted for adjuvant treatment required a median of 8 days for the first course, those who were admitted for neoadjuvant treatment required 12 days, and metastatic patients required 14 days; there were no significant differences between treatment types (<i>p</i> = 0.233). However, the median treatment time was 11.5 and 17 days, in 2020 and in 2019, respectively. A significant difference was observed between the 2 groups (<i>p</i> &#x3c; 0.001). <b><i>Conclusion:</i></b> The effective shift of workers and accurate regulations have not resulted in apparent delays in patient care. While a decrease in the number of patients has detected, faster healthcare service was introduced to newly diagnosed patients. The reason for the decrease in the number of patients should be investigated with new studies.


2020 ◽  
Vol 16 (1) ◽  
pp. 55-57
Author(s):  
Milad Shirvaliloo

It is not unbeknownst to us that since the very onset of the COVID-19 outbreak, many patients from different age groups have suffered greatly, and in a remarkable number of cases, succumbed to their untimely demise as a result of infection with the novel coronavirus or SARS-CoV- -2. The elderly are perhaps the most vulnerable community, who stand at the pinnacle of morbidity and mortality rates due to contracting severe forms of COVID-19. Hopefully, based on the recent findings and the present evidence, there might be a number of medications that would possibly be of great prophylactic and therapeutic value to the elderly patients diagnosed with COVID-19. According to an interventional study, Thymosin α1 is arguably one such medication that has recently been indicated to be an effective therapeutic agent for inpatient management of lymphocytopenia and T cell exhaustion caused by COVID-19.


Author(s):  
Habeb Al-Kamel ◽  
Oliver Grundmann

: COVID-19 is an emerging viral infection of zoonotic origin that is closely related to the severe acute respiratory syndrome coronavirus (SARS-CoV) that caused an outbreak in 2003. Therefore, scientists named the new virus SARS-CoV-2. On March 11, 2020, The World Health Organization (WHO) recognized COVID-19 as a global pandemic. At present, three vaccines have been approved or are being considered for approval by national regulatory agencies to immunize against COVID-19. However, the vaccines do not yet remain widely available and no specific treatment against the virus is available. The pathogenesis and proliferation pathways of SARS-CoV-2 are still not well known. Thus, in this article, the saponin glycyrrhizin is discussed as a new potential therapeutic agent of natural origin (licorice root, Glycyrrhizaglabra) for the potential treatment of COVID-19 infections.


2020 ◽  
Vol 6 (4) ◽  
pp. 00385-2020
Author(s):  
Daniel H.L. Lemmers ◽  
Mohammed Abu Hilal ◽  
Claudio Bnà ◽  
Chiara Prezioso ◽  
Erika Cavallo ◽  
...  

BackgroundIn mechanically ventilated acute respiratory distress syndrome (ARDS) patients infected with the novel coronavirus disease (COVID-19), we frequently recognised the development of pneumomediastinum and/or subcutaneous emphysema despite employing a protective mechanical ventilation strategy. The purpose of this study was to determine if the incidence of pneumomediastinum/subcutaneous emphysema in COVID-19 patients was higher than in ARDS patients without COVID-19 and if this difference could be attributed to barotrauma or to lung frailty.MethodsWe identified both a cohort of patients with ARDS and COVID-19 (CoV-ARDS), and a cohort of patients with ARDS from other causes (noCoV-ARDS).Patients with CoV-ARDS were admitted to an intensive care unit (ICU) during the COVID-19 pandemic and had microbiologically confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. NoCoV-ARDS was identified by an ARDS diagnosis in the 5 years before the COVID-19 pandemic period.ResultsPneumomediastinum/subcutaneous emphysema occurred in 23 out of 169 (13.6%) patients with CoV-ARDS and in three out of 163 (1.9%) patients with noCoV-ARDS (p<0.001). Mortality was 56.5% in CoV-ARDS patients with pneumomediastinum/subcutaneous emphysema and 50% in patients without pneumomediastinum (p=0.46).CoV-ARDS patients had a high incidence of pneumomediastinum/subcutaneous emphysema despite the use of low tidal volume (5.9±0.8 mL·kg−1 ideal body weight) and low airway pressure (plateau pressure 23±4 cmH2O).ConclusionsWe observed a seven-fold increase in pneumomediastinum/subcutaneous emphysema in CoV-ARDS. An increased lung frailty in CoV-ARDS could explain this finding more than barotrauma, which, according to its etymology, refers to high transpulmonary pressure.


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