COVID super-immunity: one of the pandemic's great puzzles

Health

Nature.com 14 October, 2021 - 10:55am

Faced with the prospect of a broad crackdown from federal enforcers, crypto firms are increasingly trying to make the argument in Washington that the old rules shouldn’t apply. To shape the debate, they’re releasing their own policy proposals that would shield them from multiple regulators and even temporarily exempt them from some regulation altogether.

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Study reveals a highly effective COVID-19 screening system utilizing a live cell-based assay

News-Medical.Net 14 October, 2021 - 08:02pm

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Coronavirus disease 19 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the five worldwide pandemics that has caused the highest fatality rates. COVID-19 is the third zoonotic coronavirus (CoV) pandemic that has occurred in the last 20 years; thus, this indicates that there are ample possibilities of future novel CoV outbreaks.

The high transmissibility of SARS-CoV-2, insufficient vaccinations, and the emergence of various SARS-CoV-2 variants suggest that this virus is highly likely to become an endemic and will therefore continue to pose a serious threat to humans. Effective antivirals that specifically target the most conserved viral enzymes would be an important mechanism for treatment against future novel CoVs.

At present, the most effective antivirals against COVID-19 are immune modulators that help to reduce the cytokine storm resulting from severe COVD-19. Presently remdesivir is the only antiviral that has been approved by the United States Food and Drug Administration (FDA) against SARS-CoV-2. Remdesivir is a repurposed ribonucleic acid (RNA)-dependent RNA polymerase (RdRp) inhibitor that is used for the treatment of COVID-19.

Two viral enzymes that can be targeted for in future effective antivirals are viral genome polymerases like RdRp, as well as virus-specific proteases that cleave the viral polyprotein into functional proteins. The efficacy of remdesivir has been found to be limited; however, remdesivir combined with a SARS-CoV-2 protease inhibitor could be highly effective against COVID-19.

SARS-CoV-2 encodes for two viral proteases, out of which CoV 3-chymotrypsin-like Main Protease (Mpro) is the more vital one. Mpro is involved in the generation of mature CoV non-structural proteins, including the RdRp subunits. Since Mpro is essential for the production of the viral genome replicase, it could be used for the development of a cell-based drug screening system.

A new study published in Antiviral Research aimed to report a cell-based assay that involved the isolation and quantification of SARS-CoV-2 Mpro in human cells in the absence of other proteins. The dose-response of drug activity against SARS-CoV-2 Mpro was evaluated, along with recovery of Mpro function after the drug was removed.

The current study involved HEK293 cells for determining the effect of drugs on the intracellular expression, as well as the function of Mpro. Specific deoxyribonucleic acid (DNA) plasmids were constructed for the expression of Mpro in these cells.

The total proteins were extracted from both transfected and untransfected cells that were either treated with drugs or mock-treated followed by immunoblotting. This was followed by fluorescence microscopy for quantification and MTT assay for determination of the cell viability. Furthermore, Calu-3 cells were used for SARS-CoV-2 live virus manipulations and RNA isolation.

The results indicated that when the plasmid vector was expressed in HEK293 cells, it led to the production of a GST-Mpro fusion peptide. This fusion protein was found to self-cleave itself into GST and the fully functional Mpro protein.

The quantification of the protein was achieved through the use of a biosensor that involved the development of dimerization-dependent red fluorescent protein (RFP) with a caspase 3 cleavage site that was engineered between the two domains in a fusion protein construct. Cleavage of caspase 3 would result in loss of fluorescence.

The co-expression of Mpro with the biosensor resulted in cleavage of the biosensor and further led to the loss of RFP fluorescence. Furthermore, mutation of a glutamine residue in the Mpro cleavage site with alanine resulted in decreased cleavage of the biosensor and increased fluorescence as compared to wt Mro. Comparatively, mutation of the glutamine along with co-transfection with wt Mpro led to an even greater decrease in RFP cleavage and higher fluorescence.

Evaluation of SARS-CoV-2 Mpro function took place with the help of a Mpro inhibitor known as GC376. Treatment of Mpro with ten-fold dilutions of 100 to 0.01 micromolar (µM) GC376 resulted in no cleavage of the biosensor, whereas treatment with 1 µM GC376 showed recovery of fluorescence levels. Thirdly, treatment with 10 and 100 µM GC376 showed high levels of RFP fluorescence recovery. No toxicity was observed following the treatment of cells with all concentrations of GC376.

The Mpro inhibitor activity of two FDA-approved drugs, Bepridil and Alverine, were compared to GC367. The results indicated that the extent of inhibition of intracellular Mpro function was higher with GC367 as compared to the two drugs. Furthermore, recovery of Mpro function was observed through the loss of fluorescence in cells expressing Mpro when the GC367 inhibitor was removed.

The current study was quite effective in determining the importance of Mpro for the development of antivirals. Although certain FDA-approved drugs having an affinity for intracellular Mpro and can therefore be repurposed for the treatment of COVID-19.

However, these drugs failed to show promising results. Therefore, the development of new antivirals with a higher affinity for Mpro is crucial, as these agents could inhibit their function and provide protection against SARS-CoV-2 and future zoonotic coronaviruses.

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Posted in: Medical Research News | Medical Condition News | Disease/Infection News

Tags: Alanine, Antigen, Assay, Biosensor, Cell, Coronavirus, Coronavirus Disease COVID-19, Cytokine, Dentistry, DNA, Drugs, Efficacy, Fluorescence, Fluorescence Microscopy, Fluorescent Protein, Food, Genome, Glutamine, Imaging, Intracellular, Medicine, MERS-CoV, Microscopy, Mutation, Pandemic, Plasmid, Polymerase, Promoter, Protein, Remdesivir, Research, Respiratory, Ribonucleic Acid, RNA, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Syndrome, Transfection, Virus

Suchandrima has a Bachelor of Science (B.Sc.) degree in Microbiology and a Master of Science (M.Sc.) degree in Microbiology from the University of Calcutta, India. The study of health and diseases was always very important to her. In addition to Microbiology, she also gained extensive knowledge in Biochemistry, Immunology, Medical Microbiology, Metabolism, and Biotechnology as part of her master's degree.

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Bhowmik, Suchandrima. "Study reveals a highly effective COVID-19 screening system utilizing a live cell-based assay". News-Medical. 14 October 2021. <https://www.news-medical.net/news/20211014/Study-reveals-a-highly-effective-COVID-19-screening-system-utilizing-a-live-cell-based-assay.aspx>.

Bhowmik, Suchandrima. "Study reveals a highly effective COVID-19 screening system utilizing a live cell-based assay". News-Medical. https://www.news-medical.net/news/20211014/Study-reveals-a-highly-effective-COVID-19-screening-system-utilizing-a-live-cell-based-assay.aspx. (accessed October 14, 2021).

Bhowmik, Suchandrima. 2021. Study reveals a highly effective COVID-19 screening system utilizing a live cell-based assay. News-Medical, viewed 14 October 2021, https://www.news-medical.net/news/20211014/Study-reveals-a-highly-effective-COVID-19-screening-system-utilizing-a-live-cell-based-assay.aspx.

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Methods used to limit transmission of SARS-CoV-2 effective against other viruses in China

News-Medical.Net 14 October, 2021 - 08:02pm

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When coronavirus disease 2019 (COVID-19) spread across the globe last year, most attempts at controlling the disease focused on reducing transmission. As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, primarily spreads through droplet transmission, the most effective measures focused on keeping people at a safe distance from each other.

Measures to help enforce this included lockdowns, stay-at-home orders, mass closures of public spaces, and mandatory face masks in most public areas. This has had the beneficial side effect of reducing influenza, which spreads through much the same methods. This has been observed in several studies

However, very few have examined the rates of transmission of other seasonal respiratory viruses have been affected. Researchers from Shenzhen's Children's Hospital have been investigating the occurrence of these diseases while these measures were in effect to understand better how to curb their transmission.

The researchers examined patients admitted to the Shenzhen Children's Hospital with acute respiratory infections (ARIs) between September and December in 2019 and 2020. Any patients below 14 years old presenting with one or more of the following symptoms was eligible for admission into the study; cough, sore throat, body temperature above 37.5C, or dyspnea/tachypnoea.

Nasopharyngeal swabs were obtained within 24 hours of admission, and the nucleic acids were extracted and tested for 11 common respiratory pathogens, including coronaviruses, adenoviruses, and influenza. The common pathogens were: Influenza A (InfA), Influenza B (InfB), Human parainfluenza virus (HPIV), Human respiratory syncytial virus (RSV), adenoviruses (AdV), Human metapneumovirus (HMPV), Human rhinovirus (HRV), Human bocavirus (HBoV), Human coronavirus (HCoV), Chlamydia (Ch), and Mycoplasma pneumoniae (MP). These were tested for using PCR assays.

Over 5,500 children were included in the study, with around 1000 more in 2020 than in 2021. The participants were divided by age and year of admission and included an equal mix of sexes. In 2109, 80% of those tested were positive on at least one test, with 70% of these positive for only one pathogen. In 2020, 70% were positive for at least one pathogen, with 85% of these positive for only one pathogen. The most detected pathogens in 2019 were HRV, MP, and HPIV, while in 2020, MP was replaced with RSV. Five pathogens (InfA, HRV, MP, AdV, and Ch) were detected less in 2020 than 2019. In school children, all pathogens were lower in 2020.

Having evaluated the rates of each of the eleven pathogens, the researchers showed that detection of InfA, MP, HRV, and AdV decreased by a significant margin, reducing the number of drugs prescribed to combat these diseases. The COVID-19 restrictions also appeared to subvert the normal trends seen in several of these diseases.

As Shenzen is in southern China, its climate typically follows the subtropical monsoon pattern, leading to high rates of influenza in the autumn and winter. Despite this, the rates of this disease remained low across the whole year.

COVID-19 restrictions likely played a large role in this, but it is also possible that COVID-19 infection may block infection of another virus. This has been seen in several other illnesses, normally due to interference between the two species or resource competition. However, the researchers point out that fear of hospitals and pharmacies as COVID-19 hotspots may have driven away many individuals who would otherwise have been tested, resulting in artificially decreased results.

Some viruses, such as RSV, HPIV, and HMPV, showed increased detection rates during the pandemic. In the case of RSV, this may be due to the decreased instances of influenza, which is known to interfere with RSV infection.

The researchers conclude that the methods used to limit the transmission of COVID-19 are also strongly effective against several other viruses, most notably influenza, and highlight the importance of these results in helping to inform public health policymakers. These could help plan strategies to prevent and limit influenza outbreaks and inform healthcare workers and authorities of the most dangerous threats in each season.

While the study was limited in geographical location and did not examine the results across the entire year, the researchers have provided a useful and fascinating insight into the pandemic's effects, and the attempts to restrict have had on the epidemiological landscape.

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Posted in: Medical Science News | Medical Research News | Disease/Infection News

Tags: Children, Chlamydia, Coronavirus, Coronavirus Disease COVID-19, Cough, Drugs, Dyspnea, Healthcare, Hospital, Influenza, Mycoplasma, Nasopharyngeal, Pandemic, Pathogen, Public Health, Respiratory, Respiratory Syncytial Virus, Rhinovirus, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Sore Throat, Syndrome, Throat, Virus

Sam completed his MSci in Genetics at the University of Nottingham in 2019, fuelled initially by an interest in genetic ageing. As part of his degree, he also investigated the role of rnh genes in originless replication in archaea.

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Hancock, Sam. "Methods used to limit transmission of SARS-CoV-2 effective against other viruses in China". News-Medical. 14 October 2021. <https://www.news-medical.net/news/20211014/Methods-used-to-limit-transmission-of-SARS-CoV-2-effective-against-other-viruses-in-China.aspx>.

Hancock, Sam. "Methods used to limit transmission of SARS-CoV-2 effective against other viruses in China". News-Medical. https://www.news-medical.net/news/20211014/Methods-used-to-limit-transmission-of-SARS-CoV-2-effective-against-other-viruses-in-China.aspx. (accessed October 14, 2021).

Hancock, Sam. 2021. Methods used to limit transmission of SARS-CoV-2 effective against other viruses in China. News-Medical, viewed 14 October 2021, https://www.news-medical.net/news/20211014/Methods-used-to-limit-transmission-of-SARS-CoV-2-effective-against-other-viruses-in-China.aspx.

In our latest interview, News-Medical spoke to Dr. Mark Penney about how we can improve COVID-19 vaccinations through contact-tracing apps.

Dr. Rebecca Huntley and Dr. Lai Heng Foong

In this interview, we spoke to researchers about how healthcare professionals can help to address the health issues surrounding climate change.

News-Medical speaks to Professor Seung Hwan Ko about his new face mask that can adapt to your changing conditions and environment.

News-Medical.Net provides this medical information service in accordance with these terms and conditions. Please note that medical information found on this website is designed to support, not to replace the relationship between patient and physician/doctor and the medical advice they may provide.

Owned and operated by AZoNetwork, © 2000-2021

New Pandemic Origin Probe; A First for CMS and LGBTQ Care; COVID-Flu Jab Mix-up

MedPage Today 14 October, 2021 - 12:00am

by Nicole Lou, Staff Writer, MedPage Today

The WHO released its proposed roster of scientific advisors who have the "last chance" to conduct an official inquiry into the origin of how SARS-CoV-2 came to infect humans. (Reuters)

Black Americans are catching up in COVID vaccination rates. (New York Times)

Apple seeks to make AirPods a wearable health device. (Wall Street Journal)

As of Thursday at 8 a.m. EDT, the unofficial U.S. COVID-19 toll reached 44,684,338 cases and 719,546 deaths, up 112,605 cases and 2,976 deaths since this time a day ago.

Will the coming colder months extend the tail end of the Delta variant's spread? (CNN)

How pandemic restrictions may live on as tools to stamp out the flu. (The Atlantic)

After Texas Gov. Abbott banned workplace COVID vaccine mandates, former Houston Methodist employees are demanding their jobs back. (Houston Public Media)

A judge blocked a vaccine mandate for correctional officers that had been set to take effect Friday in California. (Sacramento Bee)

Melbourne is ending its months-long lockdown ahead of schedule, thanks to fast vaccine uptake in the Australian city. (Reuters)

Ebola vaccination is back on in the Democratic Republic of Congo following the death of a toddler and his family members, the WHO announced.

The WHO honored Henrietta Lacks, the provider of the HeLa cell line, with a posthumous award for her contributions to science. (Al Jazeera)

Lateral flow tests for coronavirus may be more accurate than previously thought, researchers say. (BBC)

CMS is covering gender-affirming care as an essential health benefit for the first time, starting in 2023 with one state, HHS announced.

Scientists share their experiences of being attacked or threatened during the pandemic. (Nature)

Wind makes a difference in outdoor SARS-CoV-2 transmission, says a fluid dynamics study. (Physics of Fluids)

What does waning immunity mean for people around the world who received the CoronaVac and Sinopharm vaccines? (Nature)

The National Academy of Medicine is launching a public-private partnership on reducing carbon emissions from the healthcare industry. (New England Journal of Medicine)

An Indiana pharmacy accidentally gave COVID-19 vaccines to two young children and their parents who had gone in for flu shots. (CNN)

A conversation in a Florida bar, and a man is persuaded to get a coronavirus vaccine. (Washington Post)

Vaccine holdouts in Auckland, New Zealand, are eligible for a unique experience: a Pfizer jab in an Air New Zealand plane, a tour of the hangar, service by crew members, and a commemorative boarding pass. (CNN)

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