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Archive for the ‘COVID-19’ Category


Cryo-EM disclosed how the D614G mutation changes SARS-CoV-2 spike protein structure.

Reporter: Dr. Premalata Pati, Ph.D., Postdoc

SARS-CoV-2, the virus that causes COVID-19, has had a major impact on human health globally; infecting a massive quantity of people [ADD HERE the Global Number from John Hopkins University https://coronavirus.jhu.edu/data]; causing severe disease and associated long-term health sequelae; resulting in death and excess mortality, especially among older and prone populations; interrupting altering routine healthcare services; disruptions to travel, trade, education, and many other societal functions; and more broadly having a negative impact on peoples physical and mental health.

It’s need of the hour to answer the questions like what allows the variants of SARS-CoV-2 first detected in the UK, South Africa, and Brazil to spread so quickly? How can current COVID-19 vaccines better protect against them?

Scientists from the Harvard Medical School and the Boston Children’s Hospital help answer these urgent questions. The team reports its findings in the journal “Science a paper entitled Structural impact on SARS-CoV-2 spike protein by D614G substitution. The mutation rate of the SARS-CoV-2 virus has rapidly evolved over the past few months, especially at the Spike (S) protein region of the virus, where the maximum number of mutations have been observed by the virologists.

Bing Chen, HMS professor of pediatrics at Boston Children’s, and colleagues analyzed the changes in the structure of the spike proteins with the genetic change by D614G mutation by all three variants. Hence they assessed the structure of the coronavirus spike protein down to the atomic level and revealed the reason for the quick spreading of these variants.


This model shows the structure of the spike protein in its closed configuration, in its original D614 form (left) and its mutant form (G614). In the mutant spike protein, the 630 loop (in red) stabilizes the spike, preventing it from flipping open prematurely and rendering SARS-CoV-2 more infectious.

Fig. 2 Cryo-EM structures of the full-length SARS-CoV-2 S protein carrying G614.

(A) Three structures of the G614 S trimer, representing a closed, three RBD-down conformation, an RBD-intermediate conformation and a one RBD-up conformation, were modeled based on corresponding cryo-EM density maps at 3.1-3.5Å resolution. Three protomers (a, b, c) are colored in red, blue and green, respectively. RBD locations are indicated. (B) Top views of superposition of three structures of the G614 S in (A) in ribbon representation with the structure of the prefusion trimer of the D614 S (PDB ID: 6XR8), shown in yellow. NTD and RBD of each protomer are indicated. Side views of the superposition are shown in fig. S8.

IMAGE SOURCE: Bing Chen, Ph.D., Boston Children’s Hospital, https://science.sciencemag.org/content/early/2021/03/16/science.abf2303

The work

The mutant spikes were imaged by Cryo-Electron microscopy (cryo-EM), which has resolution down to the atomic level. They found that the D614G mutation (substitution of in a single amino acid “letter” in the genetic code for the spike protein) makes the spike more stable as compared with the original SARS-CoV-2 virus. As a result, more functional spikes are available to bind to our cells’ ACE2 receptors, making the virus more contagious.


Cryo-EM revealed how the D614G mutation changes SARS-CoV-2 spike protein structure.

IMAGE SOURCE:  Zhang J, et al., Science

Say the original virus has 100 spikes,” Chen explained. “Because of the shape instability, you may have just 50 percent of them functional. In the G614 variants, you may have 90 percent that is functional. So even though they don’t bind as well, the chances are greater and you will have an infection

Forthcoming directions by Bing Chen and Team

The findings suggest the current approved COVID-19 vaccines and any vaccines in the works should include the genetic code for this mutation. Chen has quoted:

Since most of the vaccines so far—including the Moderna, Pfizer–BioNTech, Johnson & Johnson, and AstraZeneca vaccines are based on the original spike protein, adding the D614G mutation could make the vaccines better able to elicit protective neutralizing antibodies against the viral variants

Chen proposes that redesigned vaccines incorporate the code for this mutant spike protein. He believes the more stable spike shape should make any vaccine based on the spike more likely to elicit protective antibodies. Chen also has his sights set on therapeutics. He and his colleagues are further applying structural biology to better understand how SARS-CoV-2 binds to the ACE2 receptor. That could point the way to drugs that would block the virus from gaining entry to our cells.

In January, the team showed that a structurally engineered “decoy” ACE2 protein binds to SARS-CoV-2 200 times more strongly than the body’s own ACE2. The decoy potently inhibited the virus in cell culture, suggesting it could be an anti-COVID-19 treatment. Chen is now working to advance this research into animal models.

Main Source:

Abstract

Substitution for aspartic acid by glycine at position 614 in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 appears to facilitate rapid viral spread. The G614 strain and its recent variants are now the dominant circulating forms. We report here cryo-EM structures of a full-length G614 S trimer, which adopts three distinct prefusion conformations differing primarily by the position of one receptor-binding domain. A loop disordered in the D614 S trimer wedges between domains within a protomer in the G614 spike. This added interaction appears to prevent premature dissociation of the G614 trimer, effectively increasing the number of functional spikes and enhancing infectivity, and to modulate structural rearrangements for membrane fusion. These findings extend our understanding of viral entry and suggest an improved immunogen for vaccine development.

https://science.sciencemag.org/content/early/2021/03/16/science.abf2303?rss=1

Other Related Articles published in this Open Access Online Scientific Journal include the following:

COVID-19-vaccine rollout risks and challenges

Reporter : Irina Robu, PhD

https://pharmaceuticalintelligence.com/2021/02/17/covid-19-vaccine-rollout-risks-and-challenges/

COVID-19 Sequel: Neurological Impact of Social isolation been linked to poorer physical and mental health

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2021/03/30/covid-19-sequel-neurological-impact-of-social-isolation-been-linked-to-poorer-physical-and-mental-health/

Comparing COVID-19 Vaccine Schedule Combinations, or “Com-COV” – First-of-its-Kind Study will explore the Impact of using eight different Combinations of Doses and Dosing Intervals for Different COVID-19 Vaccines

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2021/02/08/comparing-covid-19-vaccine-schedule-combinations-or-com-cov-first-of-its-kind-study-will-explore-the-impact-of-using-eight-different-combinations-of-doses-and-dosing-intervals-for-diffe/

COVID-19 T-cell immune response map, immunoSEQ T-MAP COVID for research of T-cell response to SARS-CoV-2 infection

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2020/11/20/covid-19-t-cell-immune-response-map-immunoseq-t-map-covid-for-research-of-t-cell-response-to-sars-cov-2-infection/

Tiny biologic drug to fight COVID-19 show promise in animal models

Reporter : Irina Robu, PhD

https://pharmaceuticalintelligence.com/2020/10/11/tiny-biologic-drug-to-fight-covid-19-show-promise-in-animal-models/

Miniproteins against the COVID-19 Spike protein may be therapeutic

Reporter: Stephen J. Williams, PhD

https://pharmaceuticalintelligence.com/2020/09/30/miniproteins-against-the-covid-19-spike-protein-may-be-therapeutic/

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COVID-19-vaccine rollout risks and challenges

Reporter : Irina Robu, PhD

BioNTech and Pfizer and Moderna COVID-19 vaccines received Emergency Use Authorization in January 2021 in Canada, European Union, United Kingdom and United States. However, in certain places COVID-19 has hit a few hindrances such as stockpiles have accumulated, deployment to vulnerable countries and at-risk groups has been slower than expected.  Yet, experts can see the light at the end of the tunnel of the pandemic. In United States, hundred of organization take a vital role in vaccine deployment, adapting their operations to meet the demands for volume, speed and better technology. Tens of thousands of transporters, vaccine handlers, medical and pharmacy staff, and frontline workers have mandatory training on the specific characteristics of each manufacturer’s distinct vaccines.

The common operating model provides the details of end-to-end vaccine deployment. Possible areas of risk to the rapid delivery of COVID-19 vaccines in the United States include:

Raw-materials constraints in production scaling

Scaling access to material and boosting production levels can cause logistical, contractual and even diplomatic challenges, requiring new forms of collaboration. The top two US manufacturers, for example, can produce 280 million vials per year, capable of holding up to 2.8 billion doses.

Quality-assurance challenges in manufacturing

Generating yields to produce a new class of vaccines—such as those based on mRNA or viral vectors—at an unprecedented scale (1.8 billion to 2.3 billion doses by mid-2021), manufacturers have required massive volumes of inputs, a larger technical workforce.

Cold-chain logistics and storage-management challenges

Manufacturers and distributors are preparing to maintain cold-chain requirements for distribution and long-term storage of mRNA-based vaccines. Large amounts of dry ice may be needed at various locations before administration.

Increased labor requirements

Complex protocols for handling and preparing COVID-19 vaccines have the potential to strain labor capacities or divert workers from other critical roles.

Wastage at points of care

Errors in storing, preparing, or scheduling administration of doses at points of care will have significant consequences and proper on-site storage conditions are also of critical importance.

IT challenges

IT systems, including vaccine-tracking systems and immunization information systems will be vital for allocating, distributing, recording, and monitoring the deployment of vaccines.

There are several possible approaches to help mitigate each of the six risks discussed, each with practical steps for organization to take across the common operating model.

Building resilient raw-materials supplies

  • Resilience planning.Producers can partner with global suppliers of raw materials and ancillary-product manufacturers to create redundancies.
  • Collaboration between industry and government.Ongoing industry engagement with government is essential for ramping-up production and maintaining high levels of production.

 Scaling manufacturing within quality guidelines

  • Scale manufacturing in new and existing facilities.  Various digital and analytics tools can help expand capacity and scale more quickly.
  • Assure quality and yield in current facilities. By continuing to coordinate with regulators, manufacturers and authorities can certify that procedures and dosage quality meet both long-established and newly issued guidelines.
  • Establish predictable supplier plans. Each manufacturing stakeholder can follow a clearly defined plan and they can also conduct regular cross-functional risk reviews to ensure that quality.

Optimizing the cold chain

  • Build redundancy into distribution.Manufacturers, distributers should quickly identify points of failure and creating redundancies at each stage.
  • Leverage feedback loops.Reporting systems could be set up to capture supply-chain disruption events as soon as they happen, with data used to refine best practices and procedures and avoid further losses.
  • Use point-of-care stock management.Vaccine inventories can be redistributed to locations with greater demand. Strategies to avoid over stockpiling must confirm maintenance of the cold chain to prevent risks to the receiving administration site.

Addressing labor shortages

  • Use several types of point-of-care facilities.Rely on hospitals and primary-care locations for vaccine administration, in addition to retail pharmacies.
  • Streamline administration across sites.Deploying vaccines at larger, streamlined vaccination sites can be more efficient and improve patient safety, labor utilization, and speed of vaccination.

 Reducing spoilage at points of care

  • Track and monitor spoilage at points of care.Manufacturers and distributors can collaborate to establish the means to identify and trace instances of spoilage. They can learn from experience and refine guidance, training, certification, and allocation to optimize utilization of doses.
  • Pace first-dose allocation.Allocation of first doses to populations and locations where the need is greatest and the confidence in the availability of second doses is high (such as healthcare professionals and vulnerable populations in nursing homes).
  • Prioritize second doses.Authorities can help ensure that the recommended two-dose course schedule for such vaccines as the Pfizer-BioNTech, Moderna, and AstraZeneca vaccines are duly completed.
  • Establish recipient commitment.Vaccine recipients could be asked to commit to second-dose appointments at their point of care before first-dose administration.
  • Manage certification.National and local government institutions can collaborate to ensure that vaccination certifications are withheld until recipients receive their second dose.

Meeting IT challenges

  • Balance IT upgrades and resilience.Stakeholders should identify IT systems that can be relied upon in the deployment of COVID-19 vaccines and assess their ability to perform at scale.
  • Share cyberthreat intelligence.COVID-19-vaccine stakeholders should agree upon common requirements and processes for generating and sharing threat intelligence.
  • Establish means of demonstrating immunity.Manufacturers and distributers can commission systems to track and verify that vaccine recipients have demonstrated immunity. if it will release them from travel limits and other pandemic-related restrictions.

Although not one organization is involved for managing vaccine deployment, but the risks can be fully address if organizations align on lead organization to build scenarios to test responses to emerging crises. The groups could align on lead organizations to manage issues while building scenarios to test responses to emerging crises. The benefits in managing each of these risks could be demonstrated with compelling metrics and communications.  As COVID-19-vaccine rollouts commence, the steps mentioned above can be undertaken by manufactures, distributors and governments.

SOURCE

https://www.mckinsey.com/business-functions/risk/our-insights/the-risks-and-challenges-of-the-global-covid-19-vaccine-rollout?cid=other-eml-nsl-mip-mck&hlkid=19a51f848bee4d00806d2da81315f70d&hctky=2071733&hdpid=062f1841-f911-48f3-ab14-a9f92e30721f#

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Early Details of Brain Damage in COVID-19 Patients

Reporter: Irina Robu, PhD

 

COVID-19 has currently claimed more American lives than World War I, Vietnam War and the Korean war combined. And while it is mainly a respiratory disease, COVID-19 infection affects other organs, including the brain. Researchers at Harvard-affiliated Massachusetts General Hospital found that COVID patients with neurological symptoms show more than some metabolic disturbances in the brain as patients who have suffered oxygen deprivation.

During the course of the pandemic, thousand patients with COVID-19 have been seen at MGH and the severity of the neurological symptoms varies from temporary loss of smell to more severe symptoms such as dizziness, confusion, seizures, and stroke. According to the principal investigator of the study, Eva Maria Ratai, Department of Radiology used 3 Tesla Magnetic Resonance Spectroscopy (MRS) to identify neurochemical abnormalities even the structural imagining findings are normal. COVID-19 patients’ brains showed N-acetyl-aspartate (NAA) reduction, choline elevation, and myo-inositol elevation, comparable to what is seen with these metabolites in other patients with leukoencephalopathy after hypoxia without COVID.

Their research indicated that one of patients with COVID-19 indicate the most severe white matter damage, whereas another had COVID-19 associated necrotizing leukoencephalopathy at the time of imaging. And the patient that experience cardiac arrest showed subtle white matter changes on structural MR. The control cases included one patient with damage due to hypoxia from other causes: one with sepsis-related white matter damage, and a normal, age-matched, healthy volunteer.

The main question still remains whether the decrease in the oxygen of the brain is causing the white matter to change or whether the virus itself is attacking white matter. The conclusion is that MRS can be used as a disease and therapy monitoring tool.

SOURCE

Small study reveals details of brain damage in COVID-19 patients

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Mechanistic link between SARS-CoV-2 infection and increased risk of stroke using 3D printed models and human endothelial cells

Reporter: Adina Hazan, PhD

 

Kaneko, et al.  from UCLA aimed to explore why SARS-CoV-2 infection is associated with an increased rate of cerebrovascular events, including

  • ischemic stroke and
  • intracerebral hemorrhage

While some suggested mechanisms include an overall systemic inflammatory response including increasing circulating cytokines and leading to a prothrombotic state, this may be only a partial answer. A SARS-CoV-2 specific mechanism could be likely, considering that both angiotensin-converting enzyme-2 (ACE2), the receptor necessary for SARS-CoV-2 to gain entry into the cell, and SARS-CoV-2 RNA have been reportedly detected in the human brain postmortem.

One of the difficulties in studying vasculature mechanisms is that the inherent 3D shape and blood flow subject this tissue to different stressors, such as flow, that could be critically relevant during inflammation. To accurately study the effect of SARS-CoV-2 on the vasculature of the brain, the team generated 3D models of the human middle cerebral artery during intracranial artery stenosis using data from CT (computed tomography) angiography. This data was then exported with important factors included such as

  • shear stress during perfusion,
  • streamlines, and
  • flow velocity to be used to fabricate 3D models.

These tubes were then coated with endothelial cells isolated and sorted from normal human brain tissue resected during surgery. In doing so, this model could closely mimic the cellular response of the vasculature of the human brain.

Surprisingly, without this 3D tube, human derived brain endothelial cells displayed very little expression of ACE2 or, TMPRSS2 (transmembrane protease 2), a necessary cofactor for SARS-COV-2 viral entry.

Interestingly,

  • horizontal shear stress increased the expression of ACE2 and
  • increased the binding of spike protein to ACE2, especially within the stenotic portion of the 3D model.

By exposing the endothelial cells to liposomes expressing the SARS-CoV-2 spike protein, they also were able to explore key upregulated genes in the exposed cells, in which they found that

  • “binding of SARS-CoV-2 S protein triggered 83 unique genes in human brain endothelial cells”.

This included many inflammatory signals, some of which have been previously described as associated with SARS-COV-2, and others whose effects are unknown. This may provide an important foundation for exploring potential therapeutic targets in patients susceptible to cerebrovascular events.

Overall, this study shows important links between the

  • mechanisms of SARS-CoV-2 and the
  • increase in ischemic events in these patients. It also has important implications for
  • treatment for SARS-CoV-2, as high blood pressure and atherosclerosis may be increasing ACE2 expression in patients, providing the entry port for viral particles into brain endothelia.

SOURCE:

https://www.ahajournals.org/doi/10.1161/STROKEAHA.120.032764

Other related articles published in this Open Access Online Scientific Journal include the following:

The Impact of COVID-19 on the Human Heart

Reporters: Justin D. Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2020/09/29/the-impact-of-covid-19-on-the-human-heart/

 

SAR-Cov-2 is probably a vasculotropic RNA virus affecting the blood vessels: Endothelial cell infection and endotheliitis in COVID-19

Reporter: Aviva Lev-Ari, PhD, RN – Bold face and colors are my addition

https://pharmaceuticalintelligence.com/2020/06/01/sar-cov-2-is-probably-a-vasculotropic-rna-virus-affecting-the-blood-vessels-endothelial-cell-infection-and-endotheliitis-in-covid-19/

 

Diagnosis of Coronavirus Infection by Medical Imaging and Cardiovascular Impacts of Viral Infection, Aviva Lev-Ari, PhD, RN  Lead Curator – e–mail: avivalev-ari@alum.berkeley.edu

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Mysteries of COVID Smell Loss

Reported : Irina  Robu, PhD

When Covid-19 patients have smell loss it tends to be sudden and severe. They are usually don’t have a blocked, stuffy or runny nose – most people with coronavirus can still breathe freely.  Since the epidemy started in march, an estimated of 80 percent of people with COVID-19 have experience smell disturbances in addition to loss of taste and the ability to smell chemical irritants. Research has shown that smell loss is common in people with COVID-19 disease, the reason why researchers and doctors have recommended to use a diagnostic test to determine if a patient has COVID-19.

Yet, the mystery is how the new coronavirus robs patients of their senses. During the early days of the epidemic, physicians and researchers thought that COVID related loss of smell might signal that the virus makes its way into the brain through the nose, where it can do the most severe damage. According to Sandeep Robert Data, a neuroscientist at Harvard Medical School, the research data showed that the primary source is the in the nose, but more specifically in the nasal epithelium. It looks like the virus attacks the cells responsible for registering odors rather than attacking neurons directly.  

It is well known that  olfactory neurons do not have angiotensin-converting enzyme 2 (ACE2) receptors, which permit the virus entry to cells, on their surface. But sustentacular cells, which provide support for  olfactory neurons are scattered with the receptors. These cells preserve the important  balance of salt ions in the mucus that neurons rest on on to send signals to the brain. If that balance is disturbed, it could lead to a closure of neuronal signaling and loss of smell.

The sustentacular cells correspondingly deliver the metabolic and physical support necessary to keep the fingerlike cilia on the olfactory neurons wherever receptors that detect odors are disturbed. Nicolas Meunier, a neuroscientist at the Paris-Saclay University in France determined that disruption of the olfactory epithelium might explain the loss of smell. Yet, it remains unclear if the damage done by the virus or because it invades immune cells.

Since COVID-19 doesn’t cause nasal congestion, researchers have found a few clues about the loss of smell. Taste receptor cells, which detect chemicals in the saliva and sends signals to the brain do not have ACE receptors. They don’t necessarily  get infected by COVID-19, but other support cells in the tongue carry the receptor.

Researchers determined that more clues on  to how the virus obliterates smell. However, some patients have seen that after five months the ability to smell has returned but not as great as expected. That news is welcomed for patients that have suffered loss of smell due to the COVID-19 virus, yet apprehensions about long term loss of smell is a large cause of concern.

SOURCE

https://www.scientificamerican.com/article/mysteries-of-covid-smell-loss-finally-yield-some-answers1/

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The complication of Pfizer’s Vaccine Distribution’s Plan

Reporter : Irina Robu, PhD

Even though Pfizer announcing the development of safe and effective vaccine is cause for celebration, scientists and public experts face  the challenge of how to quickly make millions of doses of the vaccine and getting them to hospitals, clinics and pharmacies. But Pfizer distribution of vaccines rely on a network of companies, federal and state agencies and on the ground health workers in the midst of a pandemic that is spreading at a high rate in United States.

Before Pfizer can begin shipping its vaccine, federal and state governments must inform Pfizer of how many doses are needed along with syringes, needles and other supplies needed to administer the vaccine. In addition, employees at the locations should be trained to store and administer the vaccine and to ensure that after people are vaccinated, they return for a second dose.

The complication of Pfizer’s vaccine is that it has to be stored at minus 70 degree Celsius until before it is injected.  Pfizer is making the vaccine at facilities in Kalamazoo, Mich., and Puurs, Belgium. The doses distributed in the United States will mostly come from Kalamazoo. When they receive emergency authorization from FDA, Pfizer will send limited doses to large hospitals, pharmacies and other vulnerable groups. At the same time, nine other candidates are also in the final stage of testing.

In Kalamazoo, vaccines will go into vials, vi will go into trays (195 vials per tray) and the trays will go into specially designed cooler-type boxes (up to five trays per box).The reusable boxes, each toting between 1,000 and 5,000 doses and stuffed with dry ice, are equipped with GPS-enabled sensors. Pfizer employees will be able to monitor the boxes’ locations and temperatures as FedEx and UPS transport them to hospitals and clinics nationwide.

The minute Pfizer coolers reach their destinations, hospitals or pharmacies will have a few alternatives of  how to store the vaccine. The easiest option is using ultracold freezers, but they can stash the trays in conventional freezers for up to five days. The destinations can keep the vials in the cooler for up to 15 days as long as they replenish the dry ice and don’t open it more than twice a day.

The chief executives at Pfizer and BioNTech suggest that Pfizer is able to produce up to 50 million doses per year and only half of those will go to US. But since two doses are needed for each person, only 12.5 million doses can be vaccinated.

The other challenge is distributing the vaccine in rural areas, where if not administering the doses fast enough it can go bad. Even though Pfizer has developed and tested an effective vaccine, figuring out how to distribute it is the hardest challenge Pfizer will face.

SOURCE

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12/5/2020

Regeneron’s Covid Antibody coktail has been cleared for emergency use by the FDA. The emergency authorization for REGN-COV2, a combination of monoclonal antibodies casiriviamb and imdevimab, marks the second for the antibody therapy. The first emergency authorization was given to Eli Lily’s bamlanivimab.

The difference that REGN-COV2 is a concoction of several drugs, whereas Lilly’s treatment contains only one drug, the two emergency authorizations  are almost identical. They treat both for mild-to-moderate COVID-19 patients at least 12 years of age who are not hospitalized but are at high risk for progressing to severe COVID-19.

SOURCE

https://www.fiercepharma.com/pharma/regeneron-following-lilly-s-footsteps-wins-fda-emergency-nod-for-covid-19-antibody-cocktail


Regeneron’s new antibody cocktail drug, REGN-COV2

Reporter : Irina Robu, PhD

Regeneron,  leading biotechnology company using the power of science to bring new medicines to patients in need answered quickly to the COVID-19 pandemic and found an antibody cocktail  as the pandemic numbers increase in the U.S. The antibody cocktail, also known as REGN-COV2 antibody combination therapy is an investigational medicine, and its safety and efficacy have not been fully evaluated by any regulatory authority.

REGN-COV2 is being studied in four ongoing late-stage clinical trials: two Phase 2/3 trials for the treatment of hospitalized and non-hospitalized COVID-19 patients, Phase 3 RECOVERY trial of hospitalized COVID-19 patients in the UK, and a Phase 3 trial for the prevention of COVID-19 in uninfected people who are at high-risk of exposure to a COVID-19 patient. The Phase 3 prevention trial is being jointly conducted with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).

The company expects approval from FDA on its antibody cocktail and expect to have 2.4-gram doses ready for about 80,000 patients at the end of November and 200,000 doses at the beginning of January.  At the same time, Regeneron partnered with Roche to expand its capacity further by increasing its manufacturing capacity.

Regeneron come in COVID-19 research early this year as the outbreak was in its early stages, testing hundreds of virus-neutralizing antibodies in mice and seeing how they compared with antibodies from human survivors of the novel coronavirus.

SOURCE

https://www.fiercepharma.com/manufacturing/regeneron-predicts-300-000-covid-19-cocktail-doses-ready-by-january-and-substantially

 

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From AAAS Science News on COVID19: New CRISPR based diagnostic may shorten testing time to 5 minutes

Reporter: Stephen J. Williams, Ph.D.

 

 

 

 

 

 

 

 

 

A new CRISPR-based diagnostic could shorten wait times for coronavirus tests.

 

 

New test detects coronavirus in just 5 minutes

By Robert F. ServiceOct. 8, 2020 , 3:45 PM

Science’s COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.

 

Researchers have used CRISPR gene-editing technology to come up with a test that detects the pandemic coronavirus in just 5 minutes. The diagnostic doesn’t require expensive lab equipment to run and could potentially be deployed at doctor’s offices, schools, and office buildings.

“It looks like they have a really rock-solid test,” says Max Wilson, a molecular biologist at the University of California (UC), Santa Barbara. “It’s really quite elegant.”

CRISPR diagnostics are just one way researchers are trying to speed coronavirus testing. The new test is the fastest CRISPR-based diagnostic yet. In May, for example, two teams reported creating CRISPR-based coronavirus tests that could detect the virus in about an hour, much faster than the 24 hours needed for conventional coronavirus diagnostic tests.CRISPR tests work by identifying a sequence of RNA—about 20 RNA bases long—that is unique to SARS-CoV-2. They do so by creating a “guide” RNA that is complementary to the target RNA sequence and, thus, will bind to it in solution. When the guide binds to its target, the CRISPR tool’s Cas13 “scissors” enzyme turns on and cuts apart any nearby single-stranded RNA. These cuts release a separately introduced fluorescent particle in the test solution. When the sample is then hit with a burst of laser light, the released fluorescent particles light up, signaling the presence of the virus. These initial CRISPR tests, however, required researchers to first amplify any potential viral RNA before running it through the diagnostic to increase their odds of spotting a signal. That added complexity, cost, and time, and put a strain on scarce chemical reagents. Now, researchers led by Jennifer Doudna, who won a share of this year’s Nobel Prize in Chemistry yesterday for her co-discovery of CRISPR, report creating a novel CRISPR diagnostic that doesn’t amplify coronavirus RNA. Instead, Doudna and her colleagues spent months testing hundreds of guide RNAs to find multiple guides that work in tandem to increase the sensitivity of the test.

In a new preprint, the researchers report that with a single guide RNA, they could detect as few as 100,000 viruses per microliter of solution. And if they add a second guide RNA, they can detect as few as 100 viruses per microliter.

That’s still not as good as the conventional coronavirus diagnostic setup, which uses expensive lab-based machines to track the virus down to one virus per microliter, says Melanie Ott, a virologist at UC San Francisco who helped lead the project with Doudna. However, she says, the new setup was able to accurately identify a batch of five positive clinical samples with perfect accuracy in just 5 minutes per test, whereas the standard test can take 1 day or more to return results.

The new test has another key advantage, Wilson says: quantifying a sample’s amount of virus. When standard coronavirus tests amplify the virus’ genetic material in order to detect it, this changes the amount of genetic material present—and thus wipes out any chance of precisely quantifying just how much virus is in the sample.

By contrast, Ott’s and Doudna’s team found that the strength of the fluorescent signal was proportional to the amount of virus in their sample. That revealed not just whether a sample was positive, but also how much virus a patient had. That information can help doctors tailor treatment decisions to each patient’s condition, Wilson says.

Doudna and Ott say they and their colleagues are now working to validate their test setup and are looking into how to commercialize it.

Posted in:

doi:10.1126/science.abf1752

Robert F. Service

Bob is a news reporter for Science in Portland, Oregon, covering chemistry, materials science, and energy stories.

 

Source: https://www.sciencemag.org/news/2020/10/new-test-detects-coronavirus-just-5-minutes

Other articles on CRISPR and COVID19 can be found on our Coronavirus Portal and the following articles:

The Nobel Prize in Chemistry 2020: Emmanuelle Charpentier & Jennifer A. Doudna
The University of California has a proud legacy of winning Nobel Prizes, 68 faculty and staff have been awarded 69 Nobel Prizes.
Toaster Sized Machine Detects COVID-19
Study with important implications when considering widespread serological testing, Ab protection against re-infection with SARS-CoV-2 and the durability of vaccine protection

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Online Event: Vaccine matters: Can we cure coronavirus? An AAAS Webinar on COVID19: 8/12/2020

Reporter: Stephen J. Williams. PhD

Source: Online Event

Top on the world’s want list right now is a coronavirus vaccine. There is plenty of speculation about how and when this might become a reality, but clear answers are scarce.Science/AAAS, the world’s leading scientific organization and publisher of the Science family of journals, brings together experts in the field of coronavirus vaccine research to answer the public’s most pressing questions: What vaccines are being developed? When are we likely to get them? Are they safe? And most importantly, will they work?

link: https://view6.workcast.net/AuditoriumAuthenticator.aspx?cpak=1836435787247718&pak=8073702641735492

Presenters

Presenter
Speaker: Sarah Gilbert, Ph.D.

University of Oxford
Oxford, UK
View Bio

Presenter
Speaker: Kizzmekia Corbett, Ph.D.

National Institute of Allergy and Infectious Diseases, NIH
Bethesda, MD
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Presenter
Speaker: Kathryn M. Edwards, M.D.

Vanderbilt Vaccine Research Program
Nashville, TN
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Presenter
Speaker: Jon Cohen

Science/AAAS
San Diego, CA
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Presenter
Moderator: Sean Sanders, Ph.D.

Science/AAAS
Washington, DC
View Moderator Bio

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via Dr. Giordano Featured in Forbes Article on COVID-19 Antibody Tests in Italy and USA

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