questions and ideas
Stilbene-based natural compounds as promising drug candidates against COVID-19

Note that resveratrol is already available in the supply chain and inexpensive. J Biomol Struct Dyn . 2020 May 12;1-10. doi: 10.1080/07391102.2020.1762743. Online ahead of print. Hussain Mustatab Wahedi , Sajjad Ahmad , Sumra Wajid Abbasi PMID: 32345140 DOI: 10.1080/07391102.2020.1762743 The pandemic coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a great threat to public health. Currently, no potent medicine is available to treat COVID-19. Quest for new drugs especially from natural plant sources is an area of immense potential. The current study aimed to repurpose stilbenoid analogs, reported for some other biological activities, against SARS-CoV-2 spike protein and human ACE2 receptor complex for their affinity and stability using molecular dynamics simulation and binding free energy analysis based on molecular docking. Four compounds in total were probed for their binding affinity using molecular docking. All of the compounds showed good affinity (> -7 kcal/mol). However, fifty nanoseconds molecular dynamic simulation in aqueous solution revealed highly stable bound conformation of resveratrol to the viral protein: ACE2 receptor complex. Net free energy of binding using MM-PBSA also affirmed the stability of the resveratrol-protein complex. Based on the results, we report that stilbene based compounds in general and resveratrol, in particular, can be promising anti-COVID-19 drug candidates acting through disruption of the spike protein. Our findings in this study are promising and call for further in vitro and in vivo testing of stiblenoids, especially resveratrol against the COVID-19. Stilbenoid analogs could be potential disruptors of SARS-CoV-2 spike protein and human ACE2 receptor complex.In particular, resveratrol revealed highly stable conformation to the viral protein: ACE2 receptor complex.The strong interaction of resveratrol is affirmed by molecular dynamic simulation studies and better net free energies. Keywords: COVID-19; MM-PBSA; Stilbenoids; molecular docking; molecular dynamic simulations

Therapeutic blockade of inflammation in severe COVID-19 infection with intravenous N-acetylcysteine

Glucose 6-phosphate dehydrogenase (G6PD) deficiency facilitates human coronavirus infection due to glutathione depletion. G6PD deficiency may especially predispose to hemolysis upon coronavirus disease-2019 (COVID-19) infection when employing pro-oxidant therapy. However, glutathione depletion is reversible by N-acetylcysteine (NAC) administration. We describe a severe case of COVID-19 infection in a G6PD-deficient patient treated with hydroxychloroquine who benefited from intravenous (IV) NAC beyond reversal of hemolysis. NAC blocked hemolysis and elevation of liver enzymes, C-reactive protein (CRP), and ferritin and allowed removal from respirator and veno-venous extracorporeal membrane oxygenator and full recovery of the G6PD-deficient patient. NAC was also administered to 9 additional respirator-dependent COVID-19-infected patients without G6PD deficiency. NAC elicited clinical improvement and markedly reduced CRP in all patients and ferritin in 9/10 patients. NAC mechanism of action may involve the blockade of viral infection and the ensuing cytokine storm that warrant follow-up confirmatory studies in the setting of controlled clinical trials. Keywords: Coronavirus 19, COVID-19, N-acetylcysteine, Glutathione, Glucose 6-phosphate dehydrogenase, Mechanistic target of rapamycin, C-reactive protein, Ferritin, Respirator, Extracorporeal membrane oxygenation

Potential therapeutic effects of Resveratrol against SARS-CoV-2

Home Acta Virologica 2020 Acta Virologica Vol.64, No.3, p.276-280, 2020 --- Novel Coronavirus COVID-19 or Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), are human pathogens. Current pandemics of SARS-CoV-2 represents a major health problem worldwide, with over four million cases and more than 300,000 deaths in the world. Development of effective therapy thus became an emergency. This report aims to highlight Resveratrol as possible therapeutic candidate in SARS-CoV-2 infection. The antiviral efficacy of Resveratrol was demonstrated for several viruses, including coronavirus. Resveratrol was shown to mitigate the major pathways involved in the pathogenesis of SARS-CoV-2, including regulation of the renin-angiotensin system (RAS) and expression of angiotensin-converting enzyme 2 (ACE2), stimulation of immune system and downregulation of pro-inflammatory cytokines release. It was also reported to promote SIRT1 and p53 signaling pathways and increase cytotoxic T lymphocytes (CTLs) and natural killer (NK) immune cells. In addition, Resveratrol was demonstrated to be a stimulator of fetal hemoglobin and a potent antioxidant, by trapping reactive oxygen species (ROS). According to these reports, Resveratrol could be proposed as potential therapeutics in the treatment of SARS-CoV-2. Keywords: SARS-CoV-2; Resveratrol; antiviral activity; immune response; ACE2; oxidative stress; HbF.

The upshot of Polyphenolic compounds on immunity amid COVID-19 pandemic and other emerging communicable diseases: An appraisal

Polyphenols are a large family of more than 10,000 naturally occurring compounds, which exert countless pharmacological, biological and physiological benefits for human health including several chronic diseases such as cancer, diabetes, cardiovascular, and neurological diseases. Their role in traditional medicine, such as the use of a wide range of remedial herbs (thyme, oregano, rosemary, sage, mint, basil), has been well and long known for treating common respiratory problems and cold infections. This review reports on the most highlighted polyphenolic compounds present in up to date literature and their specific antiviral perceptive properties that might enhance the body immunity facing COVID-19, and other viral infectious diseases. In fact, several studies and clinical trials increasingly proved the role of polyphenols in controlling numerous human pathogens including SARS and MERS, which are quite similar to COVID-19 through the enhancement of host immune response against viral infections by different biological mechanisms. Thus, polyphenols ought to be considered as a potential and valuable source for designing new drugs that could be used effectively in the combat against COVID‐19 and other rigorous diseases. Keywords: Polyphenols, Natural product, COVID-19, SARS, Respiratory tract, Infectious diseases

US has potential of becoming coronavirus epicentre, says WHO

WHO spokeswoman Margaret Harris said in Geneva there had been a "very large acceleration" in coronavirus infections in the United States which had the potential of becoming the new epicenter. Over the past 24 hours, 85 percent of new cases were from Europe and the United States, she told reporters. Of those, 40 percent were from the United States. Asked whether the United States could become the new epicenter, Harris said: "We are now seeing a very large acceleration in cases in the U.S. So it does have that potential. We cannot say that is the case yet but it does have that potential." ------------------------------------------- (Source: VOA )

The Virus Can Be Stopped, but Only With Harsh Steps, Experts Say

Scientists who have fought pandemics describe difficult measures needed to defend the United States against a fast-moving pathogen. "If it were possible to wave a magic wand and make all Americans freeze in place for 14 days while sitting six feet apart, epidemiologists say, the whole epidemic would sputter to a halt. The virus would die out on every contaminated surface and, because almost everyone shows symptoms within two weeks, it would be evident who was infected. If we had enough tests for every American, even the completely asymptomatic cases could be found and isolated. The crisis would be over."

CDC: Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19) — United States, February 12–March 16, 2020

What this tells us is that nobody is immune from getting COVID-19 and potential hospitalization, which in the US is astronomically expensive. "California on Tuesday reported the first death in the United States of a Covid-19 patient younger than 18, and the family of a 12-year-old in Georgia said Sunday she was on a ventilator and fighting for her life in an Atlanta hospital. There also have been "concerning reports from France and Italy" about young people becoming seriously ill, "and very seriously ill in the ICUs," said Dr. Deborah Birx, the White House's coronavirus reponse coordinator, last week. There are now more than 52,000 cases of the virus in the United States. At least 680 people had died as of Tuesday afternoon." (Source CNN)

Drug Companies Will Make a Killing From Coronavirus Unless we fix the system, American taxpayers will get gouged on a vaccine they paid to produce.

Opinion Drug Companies Will Make a Killing From Coronavirus Unless we fix the system, American taxpayers will get gouged on a vaccine they paid to produce. By Mariana Mazzucato and Azzi Momenghalibaf Ms. Mazzucato is a professor at University College London and the author of “The Value of Everything.” Ms. Momenghalibaf is a senior program officer at the Open Society Public Health Program.

Trump's Indadequate Response

Mr. Trump is known for undermining scientists, institutions and the media. He shut down the White House National Security Council’s entire global health security unit in 2018, an error that is perhaps going to cost him dearly now. He can only sincerely hope that “one day, it’s like a miracle, it will disappear”.