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Nafamostat is expected to prevent the transmission of new coronavirus infection (COVID-19)

Nafamostat is expected to prevent the transmission of new coronavirus infection (COVID-19)

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Credit: Image: 2020 The University of Tokyo.

Nafamostat mesylate (brand name: Fusan), which is the drug used to treat acute pancreatitis, may effectively block the requisite viral entry process the new coronavirus (SARS-CoV-2) uses to spread and cause disease (COVID-19). The University of Tokyo announced these new findings on March 18, 2020.

According to the new research, Nafamostat can prevent the fusion of the envelope of the virus with host cell surface membranes, the first step in infection with the causative virus SARS-CoV-2. Nafamostat can inhibit the membrane fusion at a concentration less than one-tenth that of Camostat mesylate (brand name: Foypan), which was recently identified by a German group as an inhibitor of SARS-CoV-2 infection (Reference 1).

Both Nafamostat and Camostat were developed in Japan as treatments for pancreatitis and some other diseases. These drugs have been prescribed in Japan for many years and have adequate clinical data with regard to safety.

The University of Tokyo plans to launch clinical trials in April 2020 in order to evaluate the effectiveness of these two drugs for treating COVID-19.

Search for therapeutics from existing drugs that have been confirmed to be safe (drug repurposing) seems to be extremely worthwhile

Professor Jun-ichiro Inoue and Assistant Professor Mizuki Yamamoto of the Research Center for Asian Infectious Diseases of the Institute of Medical Science, the University of Tokyo, have identified Nafamostat as a strong candidate to fight COVID-19.

Even after the World Health Organization’s declaration of a pandemic, no drug has yet been shown to be effective for treating COVID-19 caused by the new coronavirus (SARS-CoV-2). The development of effective drugs is an urgent issue.

“Considering that SARS-CoV-2 infection is already spreading worldwide, drug repurposing (*1), which searches for therapeutics among existing drugs with established safety records, seems to be extremely worthwhile,” Inoue said.

The genomic RNA of coronaviruses such as SARS-CoV-2 is surrounded by an envelope composed of a lipid bilayer and envelope proteins. SARS-CoV-2 initiates human cell entry after the Spike protein (S protein) present on the envelope binds to a cell membrane receptor ACE2 (*2). The S protein is cleaved into S1 and S2 by a human cell-derived protease (proteolytic enzyme) that is assumed to be Furin. S1 then binds to its receptor, ACE2. The other fragment, S2, is cleaved by TMPRSS2 (*3), a human cell surface serine protease, resulting in membrane fusion. According to Hoffmann et al., ACE2 and TMPRSS2 are essential in airway cells for SARS-CoV-2 infection (Reference 1).

The research group already reported in 2016 that Nafamostat effectively inhibits MERS-CoV S protein-initiated membrane fusion. The researchers did this using the Dual Split Protein (DSP) reporter fusion assay (*4) to screen a library consisting of 1,017 FDA-approved drugs. This screening result, together with experimental data from MERS-CoV infection of cultured airway epithelial cell-derived Calu-3 cells (*5), led them to propose that Nafamostat could be effective at inhibiting MERS-CoV infection (Reference 2).

In the present study, they newly established a SARS-CoV-2 S protein-initiated fusion assay and found that in the concentration range from 10 to 1000 nM, Nafamostat suppressed SARS-CoV-2 S protein-initiated fusion utilizing 293FT cells (derived from human fetal kidney) (*6) ectopically expressing ACE2 and TMPRSS2. Then, a similar experiment was performed using Calu-3 cells, which are considered an appropriate model for the cells SARS-CoV infects in humans. Low concentrations in the 1-10 nM range of Nafamostat significantly suppressed membrane fusion. This is almost the same as the concentration range for inhibition of membrane fusion by the MERS-CoV S protein.

The research group also compared the effects of Nafamostat and Camostat. They found that Nafamostat inhibited SARS-CoV-2 S protein-initiated fusion at a concentration less than one-tenth that needed for Camostat. Based on the above explanation, they concluded that Nafamostat is the most effective drug against SARS-CoV-2 S protein-initiated fusion among the protease inhibitors used in clinical practice and tested so far.

Future potential of Nafamostat and Camostat

Nafamostat is administered clinically by intravenous infusion. The research group speculated that the blood concentration of Nafamostat after administration would exceed the concentration needed experimentally to inhibit membrane fusion via the SARS-CoV-2 S protein. Therefore, it is expected that Nafamostat will prevent SARS-CoV-2 from entering human cells. Camostat is an oral drug. Blood levels after oral administration may be inferior to Nafamostat.

“Both drugs could be used alone, or in combination with other antiviral drugs that target separate processes needed for virus production, such as RNA replication or viral protein processing,” said Inoue.

###

Research Notes

(*1) drug repurposing: An attempt to find new effective uses for existing drugs whose safety in humans has already been adequately established in clinical practice.

(*2) ACE2: Angiotensin converting enzyme 2, which catalyzes the conversion of angiotensin II to angiotensin 1-7. ACE2 acts as a receptor for both SARS-CoV and SARS-CoV-2.

(*3) TMPRSS2: Transmembrane protease, serine 2. A serine protease present in the cell surface membrane. The SARS-CoV-2 coronavirus S protein is said to undergo proteolysis by TMPRSS2 after binding to the host receptor. Absent protein degradation, membrane fusion cannot proceed. Nafamostat is thought to inhibit S protein-initiated membrane fusion by inhibiting TMPRSS2 activity.

(*4) fusion assay system: A DSP (Dual Split Protein) reporter is used to detect fusion. DSP is a chimeric protein of split Renilla luciferase and split GFP (DSP1-7, DSP8-11), which has neither activity by itself, but can regain both GFP and luciferase activity upon self-association via its split GFP domain to a partner protein. By expressing these two proteins in separate cells, fusion between the cells can be quantified based on restored GFP and luciferase activity.

(*5) Calu-3 cells: Human bronchial epithelial cell-derived immortalized cells established from human lung cancer. It is used for functional analysis of respiratory cells. These cells are our appropriate model for the lung epithelial cells that SARS-CoV2 and MERS-CoV actually infect.

(*6) 293FT cell: an immortalized cell line derived from human fetal kidney. It has excellent properties such as fast cell growth and easy gene transfer.

References

1. Hoffmann et al. Cell 181, 1-10 (2020)
https://www.sciencedirect.com/science/article/pii/S0092867420302294?via%3Dihub

2. Yamamoto et al. Antimicrob Agents Chemother 60, 6532-6539 (2016)
https://aac.asm.org/content/60/11/6532

Media Contact
Jun-ichiro Inoue
jun-i@ims.u-tokyo.ac.jp

Original Source

https://www.ims.u-tokyo.ac.jp/imsut/en/about/press/page_00002.html

Related Journal Article

http://dx.doi.org/10.1016/j.cell.2020.02.052

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Avricore Health Signs Master Agreement to Pilot HEALTHTAB™ Platform For Diabetes Management in Select Shoppers Drug Mart® Pharmacies

Avricore Health (AVCR) announces that patients will soon have access to its innovative point-of-care blood screening and health-data management platform, HealthTab™…

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VANCOUVER, BC – (GLOBE NEWSWIRE)  June 3, 2021 Avricore Health Inc. (TSXV: AVCR, OTC: AVCRF) (“Avricore Health” or the “Company”) is pleased to announce patients will soon have access to its innovative point-of-care blood screening and health-data management platform, HealthTab™, at select Shoppers Drug Mart locations. Through this pilot program, patients will have greater access to earlier diabetes detection and preventative screening services for at-risk individuals. Ultimately, the objective is to reduce the negative health impacts and support those living with diabetes achieve higher quality-of-life.

The program, as per the Master Agreement Statement of Work, will launch in eleven Shoppers Drug Mart locations in Ontario with HealthTab™-integrated Afinion2™ analyzers by Abbott Diagnostics to refine workflow and engagement approaches.  Pharmacists will test patients’ average blood sugar (HbA1C) and lipids with results reported via the cloud-based HealthTab™ system. 

“Having accessible, high-quality diagnostics with real-time data reporting and the support of a trusted Shoppers Drug Mart pharmacist is a powerful combination in the battle against chronic disease in Canada,” said Hector Bremner, CEO of Avricore Health. “This initiative is a major step forward for our mission to deliver the most accessible early disease detection and management platform in the country.”

The program’s initial focus is to screen patients at-risk for developing diabetes and cardiovascular conditions and to support those already diagnosed by a physician to better manage their conditions for higher quality of life.

“Our purpose is to help Canadians live life well and that means providing the tools and services they need to successfully manage their overall health. Lowering barriers to health information and getting more support from a qualified health professional, like one of our pharmacists, are important steps forward in mitigating disease impacts and increasing patient quality of life,” said Doug Bryce, VP, Health & Pharmacy Programs and Innovation, Shoppers Drug Mart. “We’re committed to innovations in service because it allows us to better support our customers. The HealthTab™ Diabetes platform will provide our patients living with Diabetes new program options to better manage their conditions.”

This initiative builds off the past success of HealthTab™ used in a government-funded screening program for Chronic Kidney Disease (CKD) in Canadian pharmacies.

Learn more at: https://corporate.shoppersdrugmart.ca

 

About HealthTab™ + RASTR

HealthTab™ is a proven point-of-care screening system, designed to support pharmacists evolving role. The system empowers patients to be proactive about their health by directly measuring and monitoring key safety tests and biomarkers of chronic disease. The HealthTabÔ  test is simple, fast, lab-accurate, and requires just a few drops of blood from a finger stick.  Results can be printed in-store or accessed securely online.

As part of this direction for HealthTab™ the Company developed a revolutionary model for utilizing the system’s unique ability to offer real-time evaluations of treated populations and even real-world evaluation clinical trials.

The name for this approach is Rapid Access Safety Test Reporting, or RASTR Network, whereby the network of HealthTab™ systems feedback de-identified data through to electronic health records and data management systems via its API capabilities.  This is the first platform of harmonized analyzers, with fully integrated data-flow, for blood chemistry results to be sent to consumers, their healthcare teams and sponsors; such as researchers, insurance providers and the life-science sector.

The significance of this approach to the market is the enhanced access to screening and early detection of disease, better data for physicians and pharmacists to support their patients, plus new opportunities to conduct research and ensure patient safety.  

And, with the emergence of COVID-19 and its variants, the HealthTab™ + RASTR platform can now directly report results from the Abbott ID Now™, or manually report results from rapid-tests, dramatically reducing the administration time and increasing the accuracy and speed of information sharing.

About Avricore Health Inc.

Avricore Health Inc. is committed to becoming a health innovator and applying technologies at the forefront of science to core health issues at the community pharmacy level. The Company’s goal is to empower consumers, patients and pharmacists with innovative technology, products, services and information to monitor and optimize health. www.avricorehealth.com

 

Contact:

Avricore Health Inc.

Hector Bremner, CEO 604-773-8943

info@avricorehealth.com

www.avricorehealth.com

 

Cautionary Note Regarding Forward-Looking Statements

Information in this press release that involves Avricore Health’s expectations, plans, intentions or strategies regarding the future are forward-looking statements that are not facts and involve a number of risks and uncertainties. Avricore Health generally uses words such as “outlook,” “will,” “could,” “would,” “might,” “remains,” “to be,” “plans,” “believes,” “may,” “expects,” “intends,” “anticipates,” “estimate,” “future,” “positioned,” “potential,” “project,” “remain,” “scheduled,” “set to,” “subject to,” “upcoming,” and similar expressions to help identify forward-looking statements. In this press release, forward-looking statements include statements regarding: the completion of the placement and the expected timing thereof and the Company’s expected use of proceeds from the placement; the unique features that the HealthTab™ platform offers to pharmacists and patients. Forward-looking statements reflect the then-current expectations, beliefs, assumptions, estimates and forecasts of Avricore Health’s management. The forward-looking statements in this press release are based upon information available to Avricore Health as of the date of this press release. Forward-looking statements believed to be true when made may ultimately prove to be incorrect. These statements are not guarantees of the future performance of Avricore Health and are subject to a number of risks, uncertainties and other factors, some of which are beyond its control and may cause actual results to differ materially from current expectations, including without limitation: failure to meet regulatory requirements; changes in the market; potential downturns in economic conditions; and other risk factors described in Avricore’s public filings. These forward-looking statements speak only as of the date on which they are made, and the Company undertakes no obligation to update them publicly to reflect new information or the occurrence of future events or circumstances, unless otherwise required to do so by law.

 

Neither the TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy 

Ira Rotenberg
Author: Ira Rotenberg

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“Next Level Dystopian Sh*t”: Amazon Rolls Out Portable Panic Booth For Warehouse Employees To Collect Themselves

"Next Level Dystopian Sh*t": Amazon Rolls Out Portable Panic Booth For Warehouse Employees To Collect Themselves

After years of reports of Amazon warehouse employees being forced to urinate in bottles, forego medical care, and work through…

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"Next Level Dystopian Sh*t": Amazon Rolls Out Portable Panic Booth For Warehouse Employees To Collect Themselves

After years of reports of Amazon warehouse employees being forced to urinate in bottles, forego medical care, and work through injuries - causing hundreds to launch petitions and revolt, the online retail giant has come up with a solution...

...a special sensory deprivation booth that allows stressed out employees to collect themselves before heading back out to the floor.

Known simply as the “ZenBooth,” the new apparatus, according to a video released by the company on Wednesday, is an “interactive kiosk where you can navigate through a library of mental health and mindful practices to recharge that internal battery.” -daily dot

The "ZenBooth" is part of Amazon's WorkingWell program, which allows employees to "recharge and reenergize" with a series of "physical and mental activities, wellness exercises, and healthy eating support."

The panic booth features a small fan, some plants, and a library of meditation videos. Hopefully it features a toilet too.

(Did we mention most COVID-19 transmission occurs via aerosolized particles hanging in the air, particularly in poorly ventilated spaces?)

As the daily dot notes, the announcement received lots of pushback from Twitter users.

"why not just improve working conditions?" said one user.

"Or you could pay your employees well, not treat them like garbage, and accept unionization," added another.

"This is some next level dystopian shit. Maybe just pay people more and let them have bathroom breaks," read yet another tweet.

At least this is a step up from their now-abandoned, patented 'worker cages.'

Tyler Durden Fri, 05/28/2021 - 19:20

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Avricore Health’s CEO Discusses Abbott Diagnostics and Rapid COVID-19 Testing Rollout

Hector Bremner, CEO of Avricore Health Inc. (AVCR:CSE & AVCRF:OTC) Explains How HealthTab works with Abbott’s IDNow for Rapid COVID-19 testing

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The following is an interview with Hector Bremner, CEO of Avricore Health Inc. (AVCR:CSE & AVCRF:OTC)

Avricore Health Inc. (AVCR) has been generating a lot of interest and excitement recently on the news of a partnership with U.S. health giant Abbott Laboratories and sizeable financings. In an exclusive interview, Avricore CEO Hector Bremner explains the upside at the Vancouver-based company.

Corona Stocks: Investors have zeroed in on your relationship with Abbott Diagnostics. Can you explain how you are well positioned to assist in Canada’s COVID-19 response? 

Hector Bremner: For us it is huge. Abbott’s commitment to human health and point of care is by far second to none. Abbott is as equally focused on pharmacy as us and we have been really grateful to their team, we work quite closely right now and we think that relationship is going to mature over this year. Their device offerings have been fantastic and offer us the type of product offerings that we think fit pharmacy, particularly with the Afinion 2 which is the device that this quarter people will read and see a bit about from us. The Afinion 2 is a blood chemistry device, uses a very small sample, it is right there in the pharmacy. The test is conducted right there and it is screening for diabetes, conducting an A1C test and also testing lipids. So we think that the relationship with Abbott has been really tremendous. It is a really powerful partnership. We have this totally unique service that really brings the devices to life. 

Corona Stocks: There was a disclosure that you are meeting with federal health officials along with Abbott and you are together seeking a federal government contract to create a platform using Abbott’s ID Now molecular testing device and Avicore’s HealthTab to test patients for COVID-19. The platform would use Avicore’s software to automatically report results from Abbott’s ID Now, presumably to government health authorities.  Can you share any details on that? 

Hector Bremner: We are actively pursuing conversations at all levels of government as we think HealthTab is missing piece to a truly successful rapid testing program and this is going very well.  And, thankfully in the past few weeks, the focus of the conversation in the media and in government announcements has been moving positively towards rapid testing again. Up until very, very recently rapid testing has been seen as not as important as [getting vaccines]. Now everyone is stepping back and realizing that we are better off using these rapid tests as a way of getting a better line of sight as to what we are actually fighting, and quarantining, containing the virus into areas, really getting on top of it. You can’t fight something when you are in the dark. 

Corona Stocks: What role would you play in this effort?

Hector Bremner: Fundamentally, we are a data generating and reporting platform, so that means using HealthTab to better track test results being done with rapid tests.  There have several stories lately showing that much of the tests purchased by government have not been deployed.  We are also hearing that tests are ending up on the black market.  And, what is used, has created a lot of labor and questions about who and how to report this information to.  So, HealthTab can automate a great deal of the labor and workflow and ensure timely disclosures and increase people’s confidence in these testing programs overall.   

Corona Stocks: More testing will likely mean more cases, correct?

Hector Bremner: Yes, there was even a study this weekend that current estimates are that there are many times more cases than are ever announced at any time due to the lack of testing. We think rapid testing in 2021 and 2022 is going to play a critical role. And going forward for travel, and for certain workplaces and major events, having a real-time rapid reporting system in place to watch for virus outbreaks is something that is going to be part of the 21st century. This isn’t the first major virus outbreak over the last 20 years, it certainly has been the most impactful. We are seeing these viruses mutate very rapidly. The vaccine will get out there but we will be living with virus outbreaks. We have an incredible number of humans on the planet and they are very mobile and traveling all over the place, interacting with each other. The reality is we need to be very, very vigilant and we can’t let this happen again. Testing and real-time reporting is critical to this. 

Rapid testing, and having real-time reporting of [virus outbreaks], and breaking down the silos of communication, which is what HealthTab does, that is going to be critical to maintaining and avoiding future shutdowns.” 

Corona Stocks: COVID-19 made for a crazy year for markets, but is a net positive for Avricore, correct?

Hector Bremner: It certainly opened up a business line that didn’t exist in the sense that viral testing – our platform is really fantastic for rapid response and getting real time eyes on the pandemic. We are still in those conversations and we are very bullish on where they are going. Canada in particular hasn’t been as progressive on the rapid testing front as other jurisdictions. 

This said, we are making great strides in advancing our blood screening of diabetes and heart disease in pharmacy, and this demonstrates that while we can operate and succeed in today’s environment, we are going to excel beyond it. 

Corona Stocks: It also seems given vaccine shortages becoming political dynamite, that governments are very motivated to be seen doing something positive? 

Hector Bremner: I think so. We don’t want to do this again. This is a very costly endeavor and I am confident that the economy is going to rebound very quickly when we reopen and the fundamentals are still strong. But the reality is we got to this situation and after Bird Flu, Swine Flu, all of these outbreaks were contained and we were not vigilant, we were not taking them seriously. We need to ensure the infrastructure is there to monitor and respond quickly. We also need a healthcare approach of proactiveness.  We offer an important tools in these efforts. 

And it’s not just viruses, it’s the big costly killers like diabetes and heart disease that need more screening and monitoring.  These issues are linked, and the expenses and deaths associated with them are avoidable.  That’s our responsibility today, to act now and make tomorrow safer and healthier. 

Corona Stocks: You already have Ontario pharmacy operators endorsing HealthTab, what support do you see coming from the health care industry this year? 

Hector Bremner: Pharmacists recognize that they need to change their scope of practice. The future looks like point of care technology and cognitive services. We provide that platform so they are really leaning in on that. We know the patient has also made that decision. Good examples are 23andMe and Ancestry and health apps. With HealthTab and their community pharmacist, patients can take direct control and don’t have to spend huge amount so time to find out what they can now find out in minutes. They can walk in and learn if they have diabetes or if they already have it work with their pharmacists to manage it better. And the drug companies have already been going towards real-world evaluation and modifying the way they are doing studies to lower studies, which HealthTab facilitates in some really powerful ways.

All the players are making the decisions and right now the process is being adopted. Over the course of this year people are going to see from us that major pharmacy groups are really leaning in on the (HealthTab) system, they are going to be see drug makers and private players like insurance companies really leaning in on using our platform and trying to engage their customers better and also enhance their own operation. 

Corona Stocks: Is there a competitor to HealthTab in the market?

Hector Bremner: Not directly, everybody is sort of adjacent to us. There are a million and one health dashboard apps, as I call them, that seek to be a digital interface for healthcare.  But they are limited in terms of plug-ins and who can connect to them, which reduces their true effectiveness.  There are also B2B enterprise solutions, and there are some device specific solutions, but again we are so successful is that we bring the patient, healthcare team, and researcher together by acting as a middleware, allowing for other technologies to be enhanced by the data we are able to generate and share.  

So, our approach is entirely unique, and while someone else might have something similar, we have solved the shortcomings out there and will win the sector. It’s kind how Facebook overtook Myspace, both may seem similar, but won was just built better and put the focus on the user experience. That is what we are doing with HealthTab. 

Corona Stocks: You are raising a lot of money, $3 million in the last few months. What is the reasoning behind that?

Hector Bremner: When you are running a public company, you are actually running two businesses as the same time. You are running the actual business where you are expected to be a subject matter expert and that is more than enough to fill your day. Then you have the market side of your business which is a whole other universe of activities. We did not want to head into this year, given our very full business development hopper, being split in our focus.

So late last year and into January-February we wanted to make sure we were fully capitalized, we will be debt free at the close of this current round and we will have sufficient capital to roll out what we plan to this year. As much of a dumpster fire that 2020 was, Avricore had a 10X year and we’re going to have another one. We think that we have got a lot of wind at our backs. 

Corona Stocks: With your government background, coming to Avricore a year ago, it seems like the company is much more focused today on delivering the promise of HealthTab and playing a key role in fighting COVID-19. 

Hector Bremner: My career has largely been in strategic communications and turning things around. We were no doubt in a tough situation when I first got involved, however we’ve done the hard work and sacrifices it takes to succeed and today, we are much more focused.  

We fundamentally believe that all the sacrifices, all the hard work, were worth it because HealthTab is just that important. This team has done so much. Roger Seccombe, who developed HealthTab, our CTO, and everybody involved, they have all leaned in and made a lot of sacrifices, especially last year. 

Today, we are getting to a place where other people are starting to now see it too and we are really excited. There are big things to come.

Sign up now – and never miss out on important news or information on Avricore Health.

 
 
Ira Rotenberg
Author: Ira Rotenberg

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