New probe that mimics coronavirus may speed up drug discovery, say scientists

Agencies
September 22, 2020

Scientists have developed a new tool that mimics how the novel coronavirus which causes COVID-19 enters and infects cells, an advance that could potentially speed up the search for treatments against the deadly disease.

The novel tool, described in the journal ACS Nano, is a fluorescent nanoparticle probe with the spike protein that is present on the surface of the SARS-CoV-2 virus, which it uses to bind to human cells and enter them.

According to the researchers, including those from the National Center for Advancing Translational Sciences (NCATS) in the US, the probe could be used in tests to rapidly gauge the ability of therapeutics to block the actual virus from infecting human cells.

"Our goal is to create a screening system to find compounds that block SARS-CoV-2 from binding to cells and infecting them," explained Kirill Gorshkov, a co-author of the study from the Naval Research Laboratory (NRL) in the US.

Since using the actual virus in such screening studies would be difficult and require special facilities, the scientists said they used nanoparticles to mimic the viral function of binding to and invading the host human cell.

"We at NRL are experts in nanoparticles, and the NCATS researchers are experts in drug screening using cellular systems. So, it was the perfect match," explained Eunkeu Oh, another co-author of the study from NRL.

To create the probe, the scientists built an ultrasmall fluorescent particle called a quantum dot, fashioned from cadmium and selenium.

According to the researchers, these particles are at around 10 nanometers in size, which makes them 3,000 times smaller than the width of a single human hair.

They studded the quantum dots' surfaces with a section of the SARS-CoV-2 spike protein which binds to ACE2 -- a human cell surface protein.

The study noted that the first step in the pathway to novel coronavirus infection is the union of the spike protein with ACE2.

The scientists could track the dots' behaviour under a microscope based on their fluorescent glow.

"Because they're such bright fluorescent objects, the quantum dots give us a powerful system to track viral attachment and effects on the cell in real time," Gorshkov said.

The researchers observed how the nanoparticle probes attach to ACE2 in a lung cell line commonly used in coronavirus assays.

According to the scientists, the probes were not toxic to the test cells at the concentrations and exposure times used in the study.

While the quantum dots followed the SARS-CoV-2 pathway into cells, they said the probes also mimicked the virus in the presence of antibodies, which are proteins made by the immune system that can specifically neutralise invading foreign agents like viruses.

The study noted that the antibodies were potent inhibitors of the quantum dot probes as well, preventing them from binding to ACE2 and entering human cells.

Based on the observation, the researchers said the quantum dot probes could help rapidly test the ability of potential therapeutic agents to block the virus from entering and infecting cells.

They said assays using the probes could also determine the concentrations at which potential treatments may safely and effectively block infection.

"Using the quantum dots, we could create tests to use in drug screening and drug repurposing, using libraries of compounds that have activity but that also are approved by the U.S. Food and Drug Administration," Gorshkov said.

"Such assays could rapidly identify promising, safe treatments for COVID-19," he added.

The scientists believe the probe's flexible design can allow researchers to swap in spikes that bind to other receptors as well since ACE2 may not be the only protein SARS-CoV-2 targets.

According to the researchers, the probe could also be used to test how mutations in the spike change the way the virus behaves by adding mutated spikes to the quantum dots.

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Agencies
October 28,2020

Washington, Oct 28: Drugmakers Sanofi and GlaxoSmithKline have agreed to provide 200 million doses of their potential COVID-19 vaccine to the COVAX Facility, a collaboration designed to give countries around the world equal access to coronavirus vaccines.

The Sanofi-GSK vaccine candidate is in early stage trials, with results expected in early December. The drugmakers said Wednesday that they plan to begin phase three trial by the end of the year and request regulatory approval of the vaccine in the first half of 2021.

The facility is part of COVAX, a coalition of governments, health organisations, businesses and charities working to accelerate the development of COVID-19 vaccines.

Thomas Triomphe, head of Sanofi's vaccine unit, said: To address a global health crisis of this magnitude, it takes unique partnerships. The commitment we are announcing today for the COVAX Facility can help us together stand a better chance of bringing the pandemic under control.

Almost 44 million people have been confirmed to be infected with the virus worldwide and 1.16 million of them have died, according to a tally by Johns Hopkins University.

Experts say the true toll of the pandemic is much greater than that, due to limited testing, missed mild cases and concealment of cases by some governments.

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News Network
October 26,2020

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Houston: Indian and Pakistani women are diagnosed with breast cancer, including more aggressive forms, at a younger age, according to a study that provides an insight into understanding the risk factors influencing the disease.

The study, published in the International Journal of Cancer, examined the characteristics of breast cancer among Indian and Pakistani-American and non-Hispanic white women in the US using data from the National Cancer Institute's Surveillance, Epidemiology and End Results Program.

Both, Indian and Pakistani women are diagnosed with more aggressive forms of the disease, at a younger age, according to the researchers.

The researchers, who are part of the Rutgers School of Public Health and Rutgers Cancer Institute of New Jersey, reviewed incidence data among Indian and Pakistani women between 1990 and 2014.

"Our results provide an insight into breast cancer in Indian and Pakistani women, suggesting several hypotheses to guide future scientific studies to better understand the risk factors influencing disease etiology and prognosis," said Jaya M Satagopan, lead author and director of the Center for South Asian Quantitative Health and Education at the Rutgers School of Public Health.

South Asians are the fastest-growing major ethnic group in the United States with breast cancer rates increasing within the population, but little is known about the disease in this socio-culturally unique population, according to the study.

The researchers also reviewed the disease characteristics, treatment and survival data between 2000 and 2016 for 4,900 Indian and Pakistani women and 482,250 non-Hispanic white women with breast cancer.

They found that the occurrence of breast cancer in Indian and Pakistani women was lower than in non-Hispanic white women, however, the number of Indian and Pakistani women diagnosed with breast cancer increased over the years.

Indian and Pakistani women with breast cancer were more likely to be diagnosed at a younger age and at more advanced stages of the disease. In addition, they received more subcutaneous or total mastectomies than non-Hispanic white women, it said.

While the researchers found that Indian and Pakistani women were less likely to die of breast cancer than their non-Hispanic white counterparts, their health was tracked for a shorter time.

Prior cancer research has shown that fewer Indian and Pakistani women participate in scientific studies and that several sociocultural factors may delay their seeking health care.

Research also has shown poor mammogram screening rates in Indian and Pakistani women, which is linked to a lack of family support, lack of transportation, modesty, fear, beliefs that cancer is divine punishment for past deeds, having lived in the United States for less than 10 years, low English proficiency and a lack of faith in the health system.

"Our study indicated that there are important differences in this population that justify further studies to better understand biological, sociocultural, and system level factors such as interactions with the health system, affecting breast cancer screening patterns, diagnosis, risk and survival among South Asian women, given the paucity of literature on this topic,” said the study's senior author Elisa V Bandera, co-leader of the Cancer Prevention and Control Research Program at Rutgers Cancer Institute of New Jersey and professor at Rutgers Robert Wood Johnson Medical School.

The study recommends identifying strategies to better engage Indian and Pakistani women in breast cancer studies and to improve interactions between health care providers and Indian and Pakistani women to identify sociocultural factors associated with screening decisions and health care use in this population.

"As the South Asian population in the United States — and especially in New Jersey — grows, it is imperative that we work to promote health equity in cancer prevention, screening, early diagnosis and treatment through community engagement and a team science approach," said Anita Kinney, director of the Center for Cancer Health Equity at Rutgers School of Public Health and Rutgers Cancer Institute of New Jersey and professor at the Rutgers School of Public Health, who is also one of the study's authors.

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Agencies
October 28,2020

An analysis of more than 80 studies reporting complications experienced by COVID-19 patients has revealed that about one-third of them have abnormalities in the frontal lobe of the brain, findings which shed light on the neurological symptoms of the disease.

The review of studies, published in Seizure: European Journal of Epilepsy, focused on abnormalities detected using electroencephalogram (EEG) scans, which are used to evaluate the electrical activity in the brain.

"We found more than 600 patients that were affected in this way. Before, when we saw this in small groups we weren't sure if this was just a coincidence, but now we can confidently say there is a connection," said Zulfi Haneef, assistant professor of neurology at Baylor College of Medicine in the US.

The scientists explained that patients are recommended an EEG test when they have a slowed reaction to stimuli, followed by seizure-like events, speech issues, confusion, or an inability to wake up after sedation.

From the review of studies, the researchers said the most common findings from the EEG were slowing or abnormal electrical discharge, mostly in the frontal lobe of the patients.

They said some of the EEG alterations found in COVID-19 patients may indicate damage to the brain that might not be repaired after recovering from the disease.

Since the brain cannot regenerate, Haneef cautioned that any damage to the organ will more than likely be permanent.

"We know that the most likely entry point for the virus is the nose, so there seems to be a connection between the part of the brain that is located directly next to that entry point," he said.

"Another interesting observation was that the average age of those affected was 61, one-third were female and two-thirds were males. This suggests that brain involvement in COVID-19 could be more common in older males," Haneef added.

However, the scientists believe more studies are needed to validate the conclusions drawn in the review research.

According to Haneef, the virus may not be directly causing the abnormal EEG readings in the brain.

He said alterations in oxygen intake, heart problems related to COVID-19, or other side effects may also be involved.

"These findings tell us that we need to try EEG on a wider range of patients, as well as other types of brain imaging, such as MRI or CT scans, that will give us a closer look at the frontal lobe," Haneef said.

"A lot of people think they will get the illness, get well and everything will go back to normal, but these findings tell us that there might be long-term issues, which is something we have suspected and now we are finding more evidence to back that up," he added.

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