Notch Therapeutics Appoints David Main as President and Chief Executive Officer to Advance the Company’s Novel Gene-Edited, iPSC-Derived Immune Cell…

TORONTO, July 20, 2020 /PRNewswire/ --Notch Therapeutics Inc., a biotechnology company creating universally compatible, off-the-shelf T cell therapies for cancer and immune disorders from renewable stem cell sources, is pleased to announce the appointment of David Main as President and Chief Executive Officer.

Notch is applying its scalable Engineered Thymic Niche (ETN) technology platform to develop homogeneous and universally compatible, stem cell-derived T cell therapies. To date, Notch has assembled a world-class scientific team and built a fully integrated, tightly controlled platform for generating and editing immune cells from clonal stem cells to enable development of a broad range of T cell therapeutics. Notch has also entered into a partnership with Allogene Therapeutics (NASDAQ: ALLO) to apply Notch's proprietary ETN platform to develop CAR-targeted, induced pluripotent stem cell (iPSC)-derived, off-the-shelf T cell or natural killer (NK) cell therapies for hematologic cancer indications.

"We have a clear goal at Notch: To create universally compatible, safe, and effective immunotherapies with the capability to treat thousands of patients from a single manufacturing run," said David Main. "The company has an internationally recognized team, a groundbreaking technology positioned to redefine and expand the clinical and commercial potential of cell therapy, and has already attracted a leading corporate partner. This is an exciting time to join and lead the company, which is now strongly positioned to advance our own pipeline of products as we also pursue additional partnering opportunities."

"We have spent the past year building a leading company developing next-generation, off-the-shelf immunotherapies driven by outstanding science and focused execution," said Ulrik Nielsen, Ph.D., Chairman of Notch. "David provides Notch with a proven industry leader and strategic thinker who has extensive experience driving and financing biotech innovation from early-stage research through commercial readiness. We are excited to bring in such outstanding leadership that is ideally suited to lead the company as it continues to advance its new class of off-the-shelf T cell therapy products."

Mr. Main is a highly experienced biopharmaceutical executive who brings to Notch more than 30 years of industry leadership experience with a strong track record of value creation and company growth. Most recently, as co-founder, Chairman, and CEO of Aquinox Pharmaceuticals, Mr. Main oversaw the advancement of the company's lead product from target validation through Phase 3 clinical trials. He also led the transition of Aquinox from a private to a NASDAQ-listed public company with approximately $300 million raised in equity capital and then completed the successful merger of Aquinox with Neoleukin Therapeutics. Prior to his leadership of Aquinox, Mr. Main served as President and CEO of INEX Pharmaceuticals and as a Vice President of QLT.

About Notch Therapeutics (www.notchtx.com) Notch is an immune cell therapy company creating universally compatible, allogeneic (off-the-shelf) T cell therapies for the treatment of cancer and immune disorders. Notch's technology platform uses genetically tailored stem cells as a renewable source for creating allogeneic T cell therapies that expand treatment options and has the potential to deliver safer, consistently manufactured and more cost-effective cell immunotherapies to patients. At the core of Notch's technology is the synthetic Engineered Thymic Niche (ETN) platform, which precisely controls the expansion and differentiation of stem cells in a process suitable for large-scale manufacturing, delivering fully defined, consistent, feeder-free and serum-free T cells that can be genetically tailored for any T cell-based immunotherapeutic application. This technology was invented in the laboratories of Juan-Carlos Ziga-Pflcker, Ph.D. at Sunnybrook Research Institute and Peter Zandstra, Ph.D., FRSC at the University of Toronto. Notch was founded by these two institutions, in conjunction with MaRS Innovation (now Toronto Innovation Acceleration Partners) and the Centre for Commercialization of Regenerative Medicine (CCRM) in Toronto.

Contact:Mary Moynihan M2Friend Biocommunications 802-951-9600 [emailprotected]

SOURCE Notch Therapeutics

Notch Therapeutics

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Notch Therapeutics Appoints David Main as President and Chief Executive Officer to Advance the Company's Novel Gene-Edited, iPSC-Derived Immune Cell...

embryonic stem cell NIH Director’s Blog

Posted on September 20th, 2016 by Dr. Francis Collins

Many people probably think of mice as unwanted household pests. But over more than a century, mice have proven to be incredibly valuable in medical research. One of many examples is how studies in mice are now helping researchers understand how mammalian genomes work, including the human genome. Scientists have spent decades inactivating, or knocking out, individual genes in laboratory mice to learn which tissues or organs are affected when a specific gene is out of order, providing valuable clues about its function.

More than a decade ago, NIH initiated a project called KOMPthe Knockout Mouse Project [1]. The goal was to use homologous recombination (exchange of similar or identical DNA) in embryonic stem cells from a standard mouse strain to knock out all of the mouse protein-coding genes. That work has led to wide availability of such cell lines to investigators with interest in specific genes, saving time and money. But its one thing to have a cell line with the gene knocked out, its even more interesting (and challenging) to determine the phenotype, or observable characteristics, of each knockout. To speed up that process in a scientifically rigorous and systematic manner, NIH and other research funding agencies teamed to launch an international research consortium to turn those embryonic stem cells into mice, and ultimately to catalogue the functions of the roughly 20,000 genes that mice and humans share. The consortium has just released an analysis of the phenotypes of the first 1,751 new lines of unique knockout mice with much more to come in the months ahead. This initial work confirms that about a third of all protein-coding genes are essential for live birth, helping to fill in a major gap in our understanding of the genome.

Posted In: Health, Science

Tags: conserved genes, embryonic development, embryonic stem cell, essential genes, genes, genetic conditions, genetics, genomics, homologous recombination, humans, International Mouse Phenotyping Consortium, knockout mice, Knockout Mouse Project, KOMP, miscarriages, mouse, phenotype, stem cells, stillbirths

Posted on July 19th, 2016 by Dr. Francis Collins

Caption: From stem cells to bone. Human bone cell progenitors, derived from stem cells, were injected under the skin of mice and formed mineralized structures containing cartilage (1-2) and bone (3). Credit: Loh KM and Chen A et al., 2016

To help people suffering from a wide array of injuries and degenerative diseases, scientists and bioengineers have long dreamed of creating new joints and organs using human stem cells. A major hurdle on the path to achieving this dream has been finding ways to steer stem cells into differentiating into all of the various types of cells needed to build these replacement parts in a fast, efficient manner.

Now, an NIH-funded team of researchers has reported important progress on this front. The researchers have identified for the first time the precise biochemical signals needed to spur human embryonic stem cells to produce 12 key types of cells, and to do so rapidly. With these biochemical recipes in hand, researchers say they should be able to generate pure populations of replacement cells in a matter of days, rather than the weeks or even months it currently takes. In fact, they have already demonstrated that their high-efficiency approach can be used to produce potentially therapeutic amounts of human bone, cartilage, and heart tissue within a very short time frame.

Posted In: Health, Science

Tags: bioengineering, Bone, cartilage, development, embryonic stem cell, heart cells, human embryonic stem cell, mesoderm, muscle cells, regenerative medicine, replacement tissue, RNA sequencing, scoliosis, stem cell differentiation, stem cells, tissue engineering

Posted on June 2nd, 2015 by Dr. Francis Collins

If youre curious what innovations are coming out of the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, take a look at this video shot via a microscope. What at first glance looks like water dripping through pipes is actually a cool new technology for swiftly and efficiently analyzing the gene activity of thousands of individual cells. You might have to watch this video several times and use the pause button to catch all of the steps, but it provides a quick overview of how the Drop-seq microfluidic device works.

First, a nanoliter-sized droplet of lysis buffer containing a bead with a barcoded sequencing primer on its surface slides downward through the straight channel at the top of the screen. At the same time, fluid containing individual cells flows through the curved channels on either side of the bead-bearing channelyou can catch a fleeting glimpse of a tiny cell in the left-hand channel about 5 seconds into the video. The two streams (barcoded-bead primers and cells) feed into a single channel where they mix, pass through an oil flow, and get pinched off into oily drops. Most are empty, but some contain a bead or a celland a few contain both. At the point where the channel takes a hard left, these drops travel over a series of bumps that cause the cell to rupture and release its messenger RNAan indicator of what genes are active in the cell. The mRNAs are captured by the primer on the bead from which, after the drops are broken, they can be transcribed, amplified, and sequenced to produce STAMPS (single-cell transcriptomes attached to microparticles). Because each bead contains its own unique barcode that enables swift identification of the transcriptomes of individual cells, this process can be done simultaneously on thousands of cells in a single reaction.

Posted In: Health, Science, Video

Tags: BRAIN Initiative, Drop-seq, embryonic stem cell, genomics, inDrop, neurology, retina, single cell analysis, technology, transciptome

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embryonic stem cell NIH Director's Blog

Clinton Vows to Fund Embryonic Stem Cell Research as …

By Peter J. Smith

WASHINGTON, D.C., October 9, 2007 (LifeSiteNews.com) - Democratic presidential candidate Hillary Rodham Clinton has promised to sign an executive order overturning President Bushs restrictions on federal funding for embryonic stem cell research once she is elected President.

The former First Lady and current junior senator from New York told her audience at the Carnegie Institution for Science that President Bush was waging a "war on science" that hindered the United States from becoming the "innovation nation."

"I will lift the current ban on ethical stem cell research," Clinton said. "The presidents ban on stem cell funding amounts to a ban on hope."

However the US has no actual ban on embryonic stem cell research. Regulations established by the Bush administration in August 2001 prohibit researchers from using federal funds to create new lines of embryonic stem cells, but it does not hinder private companies from funding their work.

"In her rush to attack the president, Hillary Clinton has conveniently forgotten that George W. Bush is the only president who has ever made federal money available for stem cell research," said Republican National Committee spokesman Danny Diaz according to Reuters.

Clintons speech also gave the impression that "ethical" stem cell research was synonymous with embryonic stem cell research, although this premise is hotly contested within the scientific community. A number of stem cell researchers reject on a practical basis any need to drive into ethically dubious territory, since stem cell therapies are continuing to be produced from non-controversial sources (e.g. adult stem cells, umbilical cord blood). On the other hand, the promise of cures from experimentation with embryonic stem cells is filled with more hot air than hope, since the cells derived from the destruction of a human embryo are naturally designed to work in the fast-developing embryonic environment and have been shownto be incompatible and tumor-causing in adult tests.

See related coverage by LifeSiteNews.com

Adult Stem Cell Research: True Potential Sacrificed for Other Possibilities Says Biotech Writer http://www.lifesitenews.com/ldn/2006/jun/06061311.html

UK Researcher: Cord Blood Real Potential for Cures, Not Embryonic Stem Cells - Part 1 http://www.lifesitenews.com/ldn/2006/aug/06081804.html

UK Researcher: Embryonic Stem Cells Have Never Been Used to Treat Anyone and no Plans Exist to do so http://www.lifesitenews.com/ldn/2006/aug/06082401.html

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Clinton Vows to Fund Embryonic Stem Cell Research as ...

Orchard Therapeutics Announces Orphan Drug and Rare Pediatric Disease Designations for OTL-203 for the Treatment of MPS-I – GlobeNewswire

July 20, 2020 07:00 ET | Source: Orchard Therapeutics (Europe) Limited

BOSTON and LONDON, July 20, 2020 (GLOBE NEWSWIRE) -- Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, today announced that the company has received both orphan drug designation and rare pediatric disease designation from the U.S Food and Drug Administration (FDA) for OTL-203, anex vivoautologous hematopoietic stem cell (HSC) gene therapy in development for the treatment of mucopolysaccharidosis type I (MPS-I).

We are pleased by the FDAs acknowledgement of the critical and urgent need to develop additional treatments for MPS-I given the severe, life-limiting nature of the disease, said Bobby Gaspar, M.D., PhD., chief executive officer of Orchard. The underlying causes of lysosomal storage disorders such as MPS-I have been notably difficult to address, and we are encouraged by the early evidence of our hematopoietic stem cell gene therapys approach to potentially treating this condition. The orphan drug and rare pediatric disease designations provide important momentum for the OTL-203 clinical program, which we remain committed to advancing as quickly as possible for patients in need.

The FDA grants orphan designation, also referred to as orphan status, to drugs intended for the treatment of rare diseases that affect fewer than 200,000 people in the US.1 This designation affords Orchard certain benefits, including tax credits for qualified clinical testing, waiver or partial payment of FDA application fees and seven years of market exclusivity, if approved.2 Separately, rare pediatric disease designations are granted for rare diseases that primarily affect children under 18 years old with recipients of this designation being awarded a priority review voucher, upon approval.3 The priority review voucher may be redeemed, transferred, or sold.4

Orchard recently announced new interim data from an ongoing proof-of-concept clinical trial evaluating the safety and efficacy of OTL-203. The first primary outcome measure was met with all eight patients achieving hematologic engraftment. Additionally, improved motor skills compared to baseline, stable cognitive scores, and normal growth was seen in the first two patients with at least one year of follow-up. Orchard expects to release full proof-of-concept results and initiate the registrational study for OTL-203 in 2021.

About OTL-203 and MPS-I Mucopolysaccharidosis type I (MPS-I) is a rare, inherited neurometabolic disease caused by a deficiency of the alpha-L-iduronidase (IDUA) lysosomal enzyme, which is required to break down sugar molecules called glycosaminoglycans (also known as GAGs). The accumulation of GAGs across multiple organ systems results in symptoms including neurocognitive impairment, skeletal deformity, loss of vision and hearing, and cardiovascular and pulmonary complications. MPS-I occurs at an overall estimated frequency of one in every 100,000 live births. There are three subtypes of MPS-I; approximately 60 percent of children born with MPS-I have the most severe subtype, called Hurler syndrome, and rarely live past the age of 10 when untreated.

Treatment options for MPS-I include hematopoietic stem cell transplant and chronic enzyme replacement therapy, both of which have significant limitations. Though early intervention with enzyme replacement therapy has been shown to delay or prevent some clinical features of the condition, it has only limited efficacy on neurological symptoms. OTL-203 is an ex vivo autologous hematopoietic stem cell gene therapy being studied for the treatment of MPS-I. Orchard was granted an exclusive worldwide license to intellectual property rights to research, develop, manufacture and commercialize the gene therapy program for the treatment of MPS-I developed by the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy.

About Orchard Orchard Therapeutics is a global gene therapy leader dedicated to transforming the lives of people affected by rare diseases through the development of innovative, potentially curative gene therapies. Our ex vivo autologous gene therapy approach harnesses the power of genetically modified blood stem cells and seeks to correct the underlying cause of disease in a single administration. In 2018, Orchard acquired GSKs rare disease gene therapy portfolio, which originated from a pioneering collaboration between GSK and theSan Raffaele Telethon Institute for Gene Therapy in Milan, Italy. Orchard now has one of the deepest and most advanced gene therapy product candidate pipelines in the industry spanning multiple therapeutic areas where the disease burden on children, families and caregivers is immense and current treatment options are limited or do not exist.

Orchard has its global headquarters in London and U.S. headquarters in Boston. For more information, please visit http://www.orchard-tx.com, and follow us on Twitter and LinkedIn.

Availability of Other Information About Orchard Investors and others should note that Orchard communicates with its investors and the public using the company website (www.orchard-tx.com), the investor relations website (ir.orchard-tx.com), and on social media (Twitter andLinkedIn), including but not limited to investor presentations and investor fact sheets,U.S. Securities and Exchange Commissionfilings, press releases, public conference calls and webcasts. The information that Orchard posts on these channels and websites could be deemed to be material information. As a result, Orchard encourages investors, the media, and others interested in Orchard to review the information that is posted on these channels, including the investor relations website, on a regular basis. This list of channels may be updated from time to time on Orchards investor relations website and may include additional social media channels. The contents of Orchards website or these channels, or any other website that may be accessed from its website or these channels, shall not be deemed incorporated by reference in any filing under the Securities Act of 1933.

Forward-Looking Statements This press release contains certain forward-looking statements about Orchards strategy, future plans and prospects, which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include express or implied statements relating to, among other things, Orchards business strategy and goals, the therapeutic potential of Orchards product candidates, including the product candidate or candidates referred to in this release, and Orchards expectations regarding the timing of clinical trials and announcement of clinical data for its product candidates and the likelihood that such data will be positive and support further clinical development and regulatory approval of these product candidates. These statements are neither promises nor guarantees and are subject to a variety of risks and uncertainties, many of which are beyond Orchards control, which could cause actual results to differ materially from those contemplated in these forward-looking statements. In particular, these risks and uncertainties include, without limitation: the severity of the impact of the COVID-19 pandemic on Orchards business, including on clinical development and commercial programs; the risk that any one or more of Orchards product candidates, including the product candidate or candidates referred to in this release, will not be approved, successfully developed or commercialized; the risk of cessation or delay of any of Orchards ongoing or planned clinical trials; the risk that Orchard may not successfully recruit or enroll a sufficient number of patients for its clinical trials; the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical studies or clinical trials will not be replicated or will not continue in ongoing or future studies or trials involving Orchards product candidates; the delay of any of Orchards regulatory submissions; the failure to obtain marketing approval from the applicable regulatory authorities for any of Orchards product candidates or the receipt of restricted marketing approvals; and the risk of delays in Orchards ability to commercialize its product candidates, if approved. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements.

Other risks and uncertainties faced by Orchard include those identified under the heading "Risk Factors" in Orchards quarterly report on Form 10-Q for the quarter ended March 31, 2020, as filed with the U.S. Securities and Exchange Commission (SEC) on May 7, 2020, as well as subsequent filings and reports filed with the SEC. The forward-looking statements contained in this press release reflect Orchards views as of the date hereof, and Orchard does not assume and specifically disclaims any obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law.

___________________________________ 1 316 Orphan Drug Act & 316.20-21: Verification of orphan-drug status (https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=316.20)

2FDA Industry Guidance: Designating an Orphan Product: Drugs and Biological Products (https://www.fda.gov/industry/developing-products-rare-diseases-conditions/designating-orphan-product-drugs-and-biological-products)

3FDA Rare Pediatric Disease Designation Voucher Programs (https://www.fda.gov/industry/developing-products-rare-diseases-conditions/rare-pediatric-disease-rpd-designation-and-voucher-programs)

4360ff Title 21 Food and Drugs (https://www.govinfo.gov/content/pkg/USCODE-2012-title21/pdf/USCODE-2012-title21-chap9-subchapV-partB-sec360ff.pdf)

Contacts

Investors Renee Leck Director, Investor Relations +1 862-242-0764 Renee.Leck@orchard-tx.com

Media Molly Cameron Manager, Corporate Communications +1 978-339-3378 media@orchard-tx.com

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Orchard Therapeutics Announces Orphan Drug and Rare Pediatric Disease Designations for OTL-203 for the Treatment of MPS-I - GlobeNewswire

Growing Infrastructure Development Projects in Asia-Pacific to Fuel Growth of the Animal Stem Cell Therapy Market 2017 2025 – Bulletin Line

According to the latest report published by PMR, the Animal Stem Cell Therapy market is anticipated to grow at a steady pace over the forecast period (2019-2029). The report sheds light on the various trends and restraining factors that are expected to shape the growth of the Animal Stem Cell Therapy in the upcoming years. The report ponders over the various parameters that are expected to impact revenue generation, sales, and demand for the Animal Stem Cell Therapy in the various regional markets.

According to the study, the Animal Stem Cell Therapy market is likely to attain a market value of ~US$ XX by 2019 and grow at a CAGR of ~XX% during the assessment period. The market study introspects the competition landscape of the Animal Stem Cell Therapy market and highlights the key developments and technological innovations witnessed in the current Animal Stem Cell Therapy market landscape.

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Animal Stem Cell Therapy Market Segmentation

The report dissects the Animal Stem Cell Therapy market into different segments to provide a fair understanding of the different aspects of the Animal Stem Cell Therapy market.

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Key Participants

The key participants in the animal stem cell therapy market are Magellan Stem Cells, ANIMAL CELL THERAPIES, Abbott Animal Hospital, VETSTEM BIOPHARMA, Veterinary Hospital and Clinic Frisco, CO, etc. The companies are entering into the collaboration and partnership to keep up the pace of the innovations.

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Growing Infrastructure Development Projects in Asia-Pacific to Fuel Growth of the Animal Stem Cell Therapy Market 2017 2025 - Bulletin Line

Market Share and Size Analysis of Cell Therapy Manufacturing Market till 2029 – 3rd Watch News

Prophecy Market Insights has recently published the Cell Therapy Manufacturing detailed market report which will help retailers, manufacturers, and distributors to understand and realize the market drivers, restraints, and opportunities to generate revenue, and trends that are instrumental in shaping the target market and its revenue.

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This segment includes factors that have emerged as key success factors and strategies adopted by key market participants.

The survey report includes a vast investigation of the geographical scene of the Cell Therapy Manufacturing market, which is manifestly arranged into the localities;

Australia, New Zealand, Rest of Asia-Pacific

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Cell Therapy ManufacturingMarket Key Players:

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Market Share and Size Analysis of Cell Therapy Manufacturing Market till 2029 - 3rd Watch News

Global Cancer Stem Cells Market 2020 by Key Players, Regions, Type and Application, Forecast to 2025 – Jewish Life News

Global Cancer Stem Cells Market 2020 by Company, Regions, Type and Application, Forecast to 2025 aimed at strengthening players overall growth and offering a strong position in their business, explores facts, events, and possible variations in the market considering regional and global levels. The report contains detailed, accurate research studies that provide an in-depth analysis of global Cancer Stem Cells market dynamics. The report highlights significant insights about the market involving market size, application, fundamental statistics, market share, and growth factors. The research incorporates an exact competitive assessment of industry players and their valuable strategies during the projected timeframe 2020 to 2025.

The report profoundly evaluated in the report covering scope, profitability, demand status, uncertainties, and development forecast. Then report compiles in-depth analysis on critical subjects of the global Cancer Stem Cells industry such as consumption, revenue, sales, production, trends, opportunities, geographic expansion, competition, segmentation, growth drivers, and challenges. The market development and other occurrences are studied to offer detailed and accurate estimates up to 2025. The study report identifies the current and forthcoming opportunities and challenges in the global market.

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NOTE: This report takes into account the current and future impacts of COVID-19 on this industry and offers you an in-dept analysis of Cancer Stem Cells market.

Key players operating in the market: Thermo Fisher Scientific, Promocell, Bionomics, Abbvie, Miltenyi Biotec, Merck Kgaa, Oncomed Pharmaceuticals, Stemline Therapeutics, Lonza, Macrogenics, Irvine Scientific, Biotime, Stemcell Technologies, Sino Biological

Market segment by product type: Cell Culturing, Cell Separation, Cell Analysis, Molecular Analysis, Others

Market segment by application: , Breast Cancer Diagnosis and Treatment, Prostate Cancer Diagnosis and Treatment, Colorectal Cancer Diagnosis and Treatment, Lung Cancer Diagnosis and Treatment, Others

Regional Segment:

Regional insights on the global Cancer Stem Cells market around several geographies have been covered in this insightful study, coupled with country-level analysis. Influential market dynamics across regional segments are slated in the report, with their magnitudes differing from country to country. Key regions split in this report: North America (United States, Canada and Mexico), Europe (Germany, France, UK, Russia and Italy), Asia-Pacific (China, Japan, Korea, India, Southeast Asia and Australia), South America (Brazil, Argentina, Colombia, Middle East and Africa (Saudi Arabia, UAE, Egypt, Nigeria and South Africa)

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Global Cancer Stem Cells Market 2020 by Key Players, Regions, Type and Application, Forecast to 2025 - Jewish Life News

3D Cell Culture Market 2020 with Top Countries Data, Global Industry Forecasts Analysis, Top Company Profiles, Competitive Landscape and Key Regions…

3D Biotek

Scope of the 3D Cell Culture Market Report:

The global 3D cell culture market is relatively concentrated; the sales of top nine manufacturers account about 68.23% of total global Production in 2016. The largest manufacture of 3D cell culture is Thermo Fisher Scientific; its Production is 252.73 K Unit in 2016. The next is Corning and Lonza Group.

North America is the largest consumption region of 3D cell culture in 2016. In 2016, the sales of 3D cell culture is about 470 K Unit in North America; its sales proportion of total global sales exceeds 36%.The next is Europe. Asia has a large growth rate of 3D cell culture.

Cancer research is currently the most well established application area and accounts for 40.05% of the present 3D culture market. Drug Discovery has also emerged quite popular with 36.25% of the current market share. Stem cells and regenerative medicine together capture a share of 24.08% in the current 3D culture market and would gradually gain focus as the market matures in the field of therapeutics in 2016. The worldwide market for 3D Cell Culture is expected to grow at a CAGR of roughly 13.5% over the next five years, will reach 970 million US$ in 2024, from 510 million US$ in 2019, according to a new Research study.

This report focuses on the 3D Cell Culture in global market, especially in North America, Europe and Asia-Pacific, South America, Middle East and Africa. This report categorizes the market based on manufacturers, regions, type and application.

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Report further studies the market development status and future 3D Cell Culture Market trend across the world. Also, it splits 3D Cell Culture market Segmentation by Type and by Applications to fully and deeply research and reveal market profile and prospects.

Major Classifications are as follows:

Geographically, this report is segmented into several key regions, with sales, revenue, market share and growth Rate of 3D Cell Culture in these regions, from 2014 to 2024, covering

This 3D Cell Culture Market Research/Analysis Report Contains Answers to your following Questions

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Major Points from Table of Contents:

1. Market Overview 1.1 3D Cell Culture Introduction 1.2 Market Analysis by Type 1.3 Market Analysis by Applications 1.4 Market Dynamics 1.4.1 Market Opportunities 1.4.2 Market Risk 1.4.3 Market Driving Force

2.Manufacturers Profiles

2.4.1 Business Overview 2.4.2 3D Cell Culture Type and Applications 2.4.2.1 Product A 2.4.2.2 Product B

3.Global 3D Cell Culture Sales, Revenue, Market Share and Competition By Manufacturer (2019-2020)

3.1 Global 3D Cell Culture Sales and Market Share by Manufacturer (2019-2020) 3.2 Global 3D Cell Culture Revenue and Market Share by Manufacturer (2019-2020) 3.3 Market Concentration Rates 3.3.1 Top 3 3D Cell Culture Manufacturer Market Share in 2020 3.3.2 Top 6 3D Cell Culture Manufacturer Market Share in 2020 3.4 Market Competition Trend

4.Global 3D Cell Culture Market Analysis by Regions

4.1 Global 3D Cell Culture Sales, Revenue and Market Share by Regions 4.1.1 Global 3D Cell Culture Sales and Market Share by Regions (2014-2019) 4.1.2 Global 3D Cell Culture Revenue and Market Share by Regions (2014-2019) 4.2 North America 3D Cell Culture Sales and Growth Rate (2014-2019) 4.3 Europe 3D Cell Culture Sales and Growth Rate (2014-2019) 4.4 Asia-Pacific 3D Cell Culture Sales and Growth Rate (2014-2019) 4.6 South America 3D Cell Culture Sales and Growth Rate (2014-2019) 4.6 Middle East and Africa 3D Cell Culture Sales and Growth Rate (2014-2019)

5.3D Cell Culture Market Forecast (2020-2024) 5.1 Global 3D Cell Culture Sales, Revenue and Growth Rate (2020-2024) 5.2 3D Cell Culture Market Forecast by Regions (2020-2024) 5.3 3D Cell Culture Market Forecast by Type (2020-2024) 5.3.1 Global 3D Cell Culture Sales Forecast by Type (2020-2024) 5.3.2 Global 3D Cell Culture Market Share Forecast by Type (2020-2024) 5.4 3D Cell Culture Market Forecast by Application (2020-2024) 5.4.1 Global 3D Cell Culture Sales Forecast by Application (2020-2024) 5.4.2 Global 3D Cell Culture Market Share Forecast by Application (2020-2024)

6.Sales Channel, Distributors, Traders and Dealers 6.1 Sales Channel 6.1.1 Direct Marketing 6.1.2 Indirect Marketing 6.1.3 Marketing Channel Future Trend 6.2 Distributors, Traders and Dealers

7.Research Findings and Conclusion

8.Appendix 8.1 Methodology 8.2 Data Source

Continued..

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Epigenetics Market to Witness an Outstanding Growth by 2025 – Cole of Duty

Global Epigenetics Market: Overview

The global epigenetics market is expected to grow at a fast paced CAGR in the next few years, owing to factors such as extensive use in the research of developmental and disease process, and growing importance of Life Science. Increasing incidences of cancer and other life threatening diseases will also drive the growth of the global epigenetics market. Epigenetic changes are extensively used in cancer research for studying tumor biology as well as to develop therapeutic drugs to fight cancer.

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Global Epigenetics Market: Trends

The recent market trend of increasingly using epigenetics for understanding the development of a disease extensively fuel the growth of this market in the coming years. Another trend that will aid the growth of the global epigenetics market is the escalating demand for personalized medicine. Extensive investments are being made by various organisations, pharmaceutical companies, and governments for the research and development of drugs, and this is another trend that is benefiting the growth of the global epigenetics market. This is because epigenetic techniques enable researchers to compare epigenetic changes between disease samples and normal samples. Public health can thus be analyzed as the changes in epigenetics are influenced by internal biological system and environment directly.

With the economies of developing countries growing faster than that of developed countries, several institutes and research facilities are being set up in the developing countries. The rise in the number of testing and research facilities, particularly in the field of biotechnology and pharmaceuticals, will lead to a rise in demand for epigenetic analysis for diagnosis of diseases and development of therapeutic drugs. This will also drive the growth prospects of the global epienetics market.

Global Epigenetics Market: Market Potential

The rise in the application of epigenetics for cancer prevention as well as cancer diagnosis thanks to technologies such as epigenetics therapy and DNA methylation to control cancer or diagnose cancer respectively, will create new opportunities of growth in the global epigenetics market. New methods such as such as ChIP and next generation sequencing (NGS) are being used to understand gene sequence which are modified due to epigenetic changes. The growing number of retail clinics, companion diagnostics, and the development of whole genome technology are pushing the demand for personalized medicine. This is also acting as a driver for the global epienetics market. As different people react differently to a particular medicine, increasing number of patients and doctors are inclined towards personalized medicine.

Investments in research and development has increased remarkably in the last few years. As investments from the developing economies pricing faster then developed nation where is research facilities is an institution setup in developing companies which is giving rise to testing biotechnology thereby giving rise to a heightened demand for disease diagnosis and development of therapeutic drugs.

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Global Epigenetics Market: Regional Outlook

The global epigenetics market is segmented on the basis of geography into Asia Pacific, North America, Europe, and the Rest of the World. Of these, North America has been leading in this market in account of the early adoption of advanced technologies and solutions. Increased investments in research and development as well as growing geriatric population, and the increasing pool patient population are some of the other factors which make North America a key market for epigenetics. In addition to North America, it is estimated the developing economies in Asia Pacific will emerge as lucrative markets for epigenetics.

Global Epigenetics Market: Competitive Landscape

Illumina, Diagenode, Abcam, CellCentric Ltd, Merck, Thermo Fisher Scientific, Zymo research, Qiagen, Chroma Therapeutics Ltd,Syndax Pharmaceuticals, Inc., Sigma-Aldrich Corporation, Eisai Co. Ltd, Oncolys Biopharma Inc., Novartis International AG, and Valirx Plc are some of the leading players within the global epienetics market.

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Epigenetics Market to Witness an Outstanding Growth by 2025 - Cole of Duty

Biological, clinical and epidemiological features of COVID-19, SARS and MERS and AutoDock simulation of ACE2 – Infectious Diseases of Poverty – BioMed…

Biological, clinical and epidemiologic features of COVID-19

The comparison of features among COVID-19, SARS-CoV and MERS-CoV is summarized in Table1.

With high-throughput sequencing, researchers announced the sequencing of SARS-CoV-2. The genome of SARS-CoV-2 consists of 6 major ORFs that are common to coronaviruses, and the sequence of SARS-CoV-2 has almost 70% similarity to that of SARS-CoV and nearly 40% similarity to that of MERS-CoV [5, 6, 11, 12]. The main differences among SARS-CoV-2, SARS-CoV and MERS-CoV are in ORF1a and the sequence of gene spike coding protein-S [5], which was identified as a key protein that interacts with target cells.

In terms of electron microscopic morphology, SARS-CoV-2 virions are generally spherical, but some are polygonal. The diameter is between 60 and 140nm. The virus particles have prominent spines that are approximately 9 to 12nm, which cause the virus to have a coronal shape. According to the virus morphology observed under the microscope, the virus is consistent with other in the coronavirus family, including SARS-CoV and MERS-CoV [5, 13].

The receptor on the target cells is the factor determining how the virus enters the cell and which tissues are susceptible, and the spike protein initiates the merging of the viral envelope with the host cell cytomembrane. Existing experimental studies have shown that ACE2 is likely to be the cell receptor of SARS-CoV-2, and SARS-CoV-2 does not use other coronavirus receptors. The main receptors of SARS-CoV and MERS-CoV are ACE2 and hDPP4 (human dipeptidyl peptidase 4 or CD26), respectively [1, 5, 14].

Although the study of COVID-19 is still in progress, our summary and comparison of coronaviruses can be useful for further research and clinical applications. The clinical symptoms of COVID-19 are similar to those of SARS and MERS, including fever, cough, myalgia and fatigue. Almost all of the patients have pneumonia, and their chest CT examinations are abnormal [1, 4, 15,16,17]. However, those who are infected with SARS-CoV-2 rarely have significant upper respiratory signs and symptoms, including nosebleed, sneezing or sore throat, which indicates that the target cell may exist in the lower respiratory tract. This is consistent with the autopsy reports of patients with COVID-19 that show that SARS-CoV-2 infection mainly causes deep airway inflammatory reactions and alveolar damage. Some patients may also have headache, hemoptysis, diarrhea, dyspnea and lymphocytopenia, but patients are less likely to have gastrointestinal symptoms [4]. Complications include acute respiratory distress syndrome, acute heart injury, and secondary infections. COVID-19 patients can be divided into those with asymptomatic, mild and severe cases. For most patients, the incubation period of the virus is generally 714days. Typically, COVID-19 gradually progresses and worsens. Thus, each patients condition becomes more serious in the second week.

COVID-19, SARS, and MERS have different mortality rates. Among them, MERS had the highest fatality rate, and COVID-19 has the lowest fatality rate. It is worth noting that watery diarrhea is common in almost 60% of patients who suffer from SARS, and there is a typical biphasic clinical course [10, 18, 19]. In MERS, most patients have symptoms that include dry cough fever, malaise, myalgia, sore throat, headache, nausea, vomiting, and diarrhea, which are similar to the symptoms of SARS, but MERS has an unpredictable and erratic clinical course [19,20,21,22]. Fibrosis and consolidation in COVID-19 are less serious than the lesions caused by SARS, revealing that in COVID-19, the chest lesions are not primarily serous inflammation but rather are exudative reactions. Whether damage to the brain, myocardium, epicardium, kidneys, spleen and digestive organs is associated with viral infection needs further research.

Next-generation sequencing (NGS) and electron microscopy technology play critical roles in the early diagnosis of COVID-19, but their diagnostic values have been weakened by the use of specific nucleic acid detection technology [11, 23]. At present, clinically confirmed patients are usually diagnosed by collecting throat swabs and then detecting the nucleic acid of SARS-CoV-2.

Diagnosis based on clinical manifestations can be an early and rapid screening method. Patients with mild symptoms may not present positive signs. Patients in severe condition may have shortness of breath, moist rales in lungs, weakened breath sounds, dullness on percussion, and changes in voice, and the physical examination can help identify these symptoms. In addition, CT imaging plays an important role in the diagnosis. The imaging features of lesions show characteristic (1) distribution (mainly subpleural, along the bronchial vascular bundles); (2) quantity (often more than three lesions, occasionally single or double lesions); (3) shape (patchy, large block, nodular, lumpy, honeycomb-like or grid-like, cord-like, etc.); (4) density (mostly uneven, crazy-paving pattern mixed with ground glass opacity and interlobular septal thickening, consolidation and thickened bronchial wall, etc.); and (5) concomitant signs (e.g., air bronchogram, rare pleural effusion and mediastinal lymph node enlargement). However, these are not enough. COVID-19 needs to be distinguished from other known viruses that cause pneumonia, such as influenza virus, parainfluenza virus, adenovirus, respiratory syncytial virus, rhinovirus, human metapneumovirus, SARS-CoV, etc. and from Mycoplasma pneumonia, Chlamydia pneumonia, and bacterial pneumonia. In addition, COVID-19 should be distinguished from noninfectious diseases, such as vasculitis, dermatomyositis, and organizing pneumonia.

Research on identifying effective drugs has started, and there have been many in vitro and in vivo experiments being conducted [24]. Vaccines against SARS-CoV-2 are currently in development, and there are at least two kinds currently ready for testing. There are approximately 15 potential vaccine candidates in the pipeline globally using a wide range of approaches (such as messenger RNA, DNA, nanoparticle, and synthetic and modified virus-like particles). The vaccine candidates will be developed by a number of organizations using DNA, recombinant and mRNA vaccine platforms109. On 23 January 2020, The Coalition for Epidemic Preparedness Innovations (CEPI) announced that they will fund vaccine development programmes with Inovio, The University of Queensland and Moderna, Inc., with the target of testing the experimental vaccines clinically. It will likely take approximately a year for most candidates to enter phase 1 clinical trials except for those funded by CEPI. For SARS, the vaccines in development include viral vector-based vaccines, DNA vaccines, subunit vaccines, virus-like particle (VLP)-based vaccines, inactivated whole-virus (IWV) vaccines and live attenuated vaccines, and the latest findings for these vaccines are based on the review by Yong et al. (2019) in August 2019 [25]. There was one SARS vaccine trial conducted by the US National Institute of Allergy and Infectious Diseases. Both Phase I clinical trials reported positive results, but only one will proceed to the Phase 2 trial. For MERS, there is only one published clinical study on a vaccine developed by GeneOne Life Science & Inovio Pharmaceuticals [26]. For therapeutics, there are nine clinical trials registered with the clinical trials registry (ClinicalTrials.gov) investigating therapeutic agents for COVID-19. Five studies on hydroxychloroquine, lopinavir plus ritonavir and arbidol, mesenchymal stem cells, traditional Chinese medicine and glucocorticoid therapy usage have commenced recruitment, and the other four are on antivirals, interferon atomization, darunavir and cobicistat, Arbidol, and remdesivir [24].

COVID-19 patients admitted to a qualified hospital are given chemotherapy, including antiviral treatment, antibiotic therapy, corticosteroid therapy and other medications, such as ibuprofen as an antipyretic, nutrition support treatment, H2 receptor antagonists or proton pump inhibitors for gastrointestinal bleeding, and selective (M1, M3) receptor anticholinergic drugs for dyspnea, coughing, wheezing, and respiratory distress syndrome. Although -interferon atomization inhalation and oral lopinavir/ritonavir can be considered, the effectiveness of the combined use of antivirals is still unknown, given the lack of evidence from a randomized controlled trial (RCT). Given the high risk of adverse effects, there are limitations on the use of corticosteroids. Traditional Chinese medicine has shown a good effect with regard to both prevention and treatment. Fumigating rooms with moxa and wearing perfumed Chinese herb bags can help prevent community transmission. Huoxiang Zhengqi capsules are recommended for hypodynamia accompanied by gastrointestinal upset caused by COVID-19. For hypodynamia and fever, Jinhua Qinggan granules, Lianhua Qingwen capsules, Shufeng Jiedu capsules and Fangfeng Tongsheng pills are recommended [23].

Nursing care is important for isolated and critically ill patients, as classified according to the guidelines. Isolated patients at home should monitor their body temperature and breathing regularly. Patients are given oxygen therapy via a nasal catheter or a mask, antiviral drugs, antibacterial drugs, symptomatic treatments, nutritional support and psychological counselling. Critically ill patients are monitored with regard to their vital signs, water-electrolyte balance, acid-base balance, and the functioning of various organs. In addition to nutritional support and psychological counselling, they need oxygen therapy and some special treatments. For example, if a patient develops moderate to severe ARDS, invasive mechanical ventilation with the patient in a prone position needs to be initiated [23, 27].

According to Yang et al., the case fatality ratio (CFR) during the first weeks of the epidemic ranged from 0.15% (95% confidence interval [CI]: 0.120.18%) in mainland China excluding Hubei t 1.41% (95% CI: 1.381.45%) in Hubei Province excluding the city of Wuhan to 5.25% (95% CI: 4.985.51%) in Wuhan City based on data from the Wuhan Municipal Health Commission and the China and National Health Commission of China [28]. Chen et al. systematically described 99 cases of COVID-19 in Wuhan, China. Critically ill patients died of severe pneumonia, septic shock, respiratory failure and multiple organ failure (MOF). The authors reached a speculative conclusion that SARS-CoV-2 is more likely to infect older adult males with chronic comorbidities as a result of their weaker immune systems. In patients with severe coinfections, immune function is important in addition to the virulence of the pathogens. Old age, obesity, and the presence of comorbidities might be associated with increased mortality. In addition, a substantial decrease in the total number of lymphocytes indicates that SARS-CoV-2 consumes many immune cells and inhibits the bodys cellular immune function; therefore, a low absolute value of lymphocytes could be used as a reference index in the diagnosis of new SARS-CoV-2 infections in the clinic [29].

It is essential to analyze the infection source, transmission route, susceptible population and replication rate, especially the intermediate host and the exact route of transmission, to find the best measures to prevent the further spread of COVID-19.

The infection sources include patients, virus carriers, and infected animals that serve as viral reservoirs. Searching for the hosts of the virus, or for the infection sources, is a vital process in understanding the viral dynamics. SARS-CoV-2 has 96.2% genetic sequence similarity to the previously identified BatCoV RaTG13, suggesting that bats are most likely to be the host of SARS-CoV-2 [1, 3, 30, 31]. The cluster of cases in the seafood market was comprehensively analyzed, and sequence comparison revealed that pangolins are the most likely intermediate host for SARS-CoV-2 [30]. However, SARS-CoV and MERS-CoV were also identified as having zoonotic origins, and the animal reservoirs seemed to be bats [9, 32]. Although bat coronaviruses are genetically related, the intermediate hosts are involved in cross-species transmission, after which human-to-human transmission developed. In contrast to SARS-CoV-2, the intermediate host of SARS-CoV was mainly palm civets [9, 33, 34], and the intermediate host of MERS-CoV was thought to be dromedary camels [22, 35]. All three coronaviruses can be traced to bats, while there are different intermediate hosts involved in cross-species transmission. These three viruses have caused widespread epidemics that originated in animal reservoirs; the high morbidity and mortality levels have caused panic and substantial economic loss.

Viruses can directly infect people but can also infect one or more kinds of animals. Although these animals themselves do not cause disease, they can act as vectors for the virus and transmit it to humans; during this process, some viruses may mutate and evolve new characteristics. According to the experimental results of Peng et al. [5], SARS-CoV-2 can be transmitted through respiratory droplets and direct contact, confirming that while the main transmission route of SARS-CoV-2 is aerosols, other routes of transmission may exist. Moreover, a recent experiment conducted with recovering patients found that SARS-CoV-2 can also exist in the patients stool, suggesting that the fecal-oral route may be a route of transmisson [36]. Li et al. investigated cases of SARS and found that SARS was spread mainly by respiratory droplets [19]. By analyzing case data, Hui et al. also found that direct person-to-person transmission through close contact can also spread SARS-CoV [18]. MERS-CoV was mainly transmitted through close contact with infected family members or infected individuals in the hospital. Xiao et al. identified seven hypothesized transmission modes based on the three main transmission routes (long-range airborne, close contact, and fomite), and the infection risks associated with each hypothesis were estimated using the multiagent modeling framework. This showed that transmission occurred via both the long-range airborne and close contact routes [22]. Based on the available data, all three coronaviruses can be transmitted by breathing respiratory droplets that contain virions, which indicates that wearing masks is an effective means of protecting susceptible people. All three coronaviruses are transmitted from animals to humans and from humans to humans.

There is no evidence that people with certain characteristics are not susceptible to COVID-19. The available data suggest that people of all ages who have close contact with patients can be infected by SARS-CoV-2 [36,37,38]. The general public is susceptible, and the data are still being updated daily. The elderly population and patients with basic diseases are more susceptible to severe illness after infection, and children and infants can also be infected by SARS-CoV-2 [39]. SARS-CoV had a tendency to affect healthier and younger persons, with a mean patient age of 39.9years (range 191), and the male to female ratio was 11.3, with a slight female predominance. MERS-CoV had a tendency to affect the elderly and frail populations, especially males, with a mean age of 56years (range 1494), and the male to female ratio was 3.31 with a male predominance [8, 10, 40].

A commonly used measure of infectivity is the basic reproduction number (R0), which is the average number of people infected who pass the virus on to others without intervention. In other words, the value is equivalent to how many people can be infected by an average patient. The larger the R0 is, the harder it is to control the epidemic. Researchers have estimated the R0 to be in the range of 2.83.9, assuming extreme cases, which means that on average a COVID-19 patient passes the virus on to 2.83.9 healthy persons [28, 41]. In comparison, the R0 of MERS has been reported to be less than 1, and the R0 of SARS is estimated to be 3. Considering that the disease is now widespread around the world, the R0 of COVID-19 may change and could be higher than those of SARS and MERS.

As of May 24, 2020, there were caused 84536 confirmed cases of COVID-19, 4645 deaths and 79757 cured cases in China. A total of 5490640 cases have been diagnosed, and 346328 deaths have occurred worldwide. SARS infected more than 8098 people in 29 countries and caused 916 deaths, with a mortality rate of approximately 10%. MERS was first found in the Arabian Peninsula and infected approximately 2254 people (from 2012 through September 16, 2018) in 27 countries; MERS caused 800 deaths, with a mortality rate of approximately 35%. SARS was characterized by superspreading events, while COVID-19 is unique for its indiscriminate transmission among the general public. However, MERS seemed to be less aggressive [8, 10, 42].

Epidemiological changes have been monitored, taking into account potential routes of transmission and subclinical infections. The official platform updates the public daily on the number of newly diagnosed cases, deaths and cures in each administrative region based on data from the Centers for Disease Control and Prevention and hospitals at all levels. Since the outbreak, many emergency measures have been taken to reduce person-to-person transmission of SARS-CoV-2. For example, public services and facilities provide disinfectants on a routine basis to encourage appropriate hand hygiene, and physical contact with wet and contaminated objects is considered when dealing with the virus, especially fecal and urine samples that can potentially serve as an alternative route of transmission. China and other countries have implemented major prevention and control measures, including screening travelers, to control further spread of the virus [43]. There are many people donating money, vegetables, medical supplies, etc. to the areas affected by the epidemic. In Wuhan, two hospitals, Vulcan Mountain Hospital and Raytheon Mountain Hospital, were built within 10 days, which can contain 1000 and 1300 patients, respectively. According to the Peoples Daily, the National Health and Fitness Commission reported that there are more than 11000 critical care workers and more than 2000 intensive care unit nurses, and there will be more pooling of medical resources in places where they are most needed. The Chinese government has shut down schools and closed businesses to reduce transmission [44].

The outbreak has also caused widespread public concern. Husnayain et al. studied the potential to use Google Trends (GT) to monitor public restlessness regarding the COVID-19 epidemic, and they found that searches related to COVID-19 and face masks increased rapidly [45]. With the advent of 5G and the rapid development of the information age, it may be more convenient for the masses to obtain the latest news from the Internet; thus, Internet-based risk communication is becoming an appropriate strategy. There are many disease control organizations and medical institutions that have played an official role in this outbreak and provided accurate and reliable information to the public in a timely manner. For example, laboratory confirmation of COVID-19 was performed in five different institutions, namely, the China CDC, Chinese Academy of Medical Science, Wuhan Institute of Virology, and Academy of Military Medical Sciences, and Chinese Academy of Sciences [29]. According to the CCTV news, with scientific progress has enabled the use of advanced technologies to control this epidemic. In addition, the health code divides the public into three health situations, namely, green, red and yellow. This provides an effective method of facilitating crowd tracking and monitoring. Furthermore, the geographic information system (GIS), which has long been used by many health professionals when tracking and combating contagion, also plays an important role in the geographical tracking and mapping of epidemics. A range of practical online/mobile GIS and mapping dashboards and applications have come into use for tracking the COVID-19 epidemic [46].

Some treatments have been adopted in clinical practice, and a few have been successful [24, 47]. According to Prashant Pradhan, the first case cured in sevendays in the United States showed that the antiviral medication remdesivir may become one of the specific medicines for COVID-19; however, this remains to be verified through clinical trials [16]. According to the research by Wang, XF, et al. about the clinical manifestations and epidemiology in children with COVID-19 treated with lopinavir and ritonavir and without glucocorticoids and immunoglobulin, all 20 patients improved and were discharged from hospital. This may lead to the conclusion that childrens clinical symptoms of COVID-19 are nonspecific and milder than those in adults, which has significant clinical value [48].

Future research priorities may be focused on biological research on SARS-CoV-2 and clinical research on COVID-19 diagnosis and treatment. According to Pradhan et al., there are four unique insertions, which have similarity to HIV, in the S-protein in COVID-19, which may explain its contagiousness. The gene binding site may become a new target of therapeutics to prevent transmission of the virus [49]. Specifically, virus particles are found in the feces, which suggests that there may exist other routes of transmission, such as fecal-oral transmission. Previously, we focused on cutting off transmission routes mainly by limiting contact and preventing respiratory droplet transmission. This finding emphasizes the significance of dealing with the feces of the patient. Therefore, for patients who already have COVID-19, careful disposal of their feces is an important concern with regard to reducing viral transmission [36]. On the basis of the research by Hongzhou Lu, lopinavir/ritonavir, nucleoside analogs, neuraminidase inhibitors, remdesivir, peptide (EK1), Arbidol, RNA synthesis inhibitors (such as TDF, 3TC), anti-inflammatory drugs (such as hormones and other molecules), Chinese traditional medicine and so on could be therapies for COVID-19, but the effects and safety remain to be tested in clinical trials [27].

3D structures of remdesivir, chloroquine, ciclesonide, niclosamide, and lopinavirus were obtained from NCBI PubChem. The crystal structure of ACE2 (PDB code: 6M17) was obtained from the Protein Data Bank. The ligands within the crystal structure complex were extracted by PyMOL software (San Carlos, CA, USA). AutoDock 4.2 was used for the docking system test. AutoDock tools initialized the ligands by adding gasteiger charges, merging nonpolar hydrogen bonds, and setting rotatable bonds. The ligands were rewritten into PDBQT format, which can be read by Autodock software (AutoDock 4.2, San Carlos, CA, USA). AutoDock Tools were used to add polar hydrogen to the entire receptor. The grid box was set to contain the entire receptor region. The receptor output was also saved in PDBQT format. AutoDock Vina was set with the macromolecule held fixed and the ligands flexible. Affinity maps for all the atom types present, as well as an electrostatic map, were computed, with a grid spacing of 0.375. The structural models were collected from the lowest-energy docking solution of each cluster of autodocks. It is evident from the findings of Fig.2 and Table2 that combinations of antiviral agents are more successful than a single drug.

AutoDock calculations were performed to determine and compare the binding affinities of remdesivir, chloroquine, ciclesonide, niclosamide, and lopinavirus to ACE2. LEU: Leucine, PHE: Phenylalanine, MET: Methionine, VAL: Valine), ILE: Isoleucine, TRP: Ttryptophan, TYR: Tyrosine

The outbreak of SARS renewed interest in this family of viruses and resulted in the development of new drugs, among which remdesivir, chloroquine, ciclesonide, niclosamide, and lopinavirus are the most promising [50,51,52]. In addition, as mentioned above, ACE2 plays a vital role in the development of COVID-19 [53]. With regard to testing the effectiveness of previous medicines used by scientists for the treatment of diseases caused by coronaviruses, AutoDock calculations have been performed to classify specific binding amino acids and thus to determine the likely common cure targets for ACE2. As shown in Table2 and Fig.2, we found that chloroquine and ciclesonide share similar binding amino acid residues (MET124, LEU127, ILE472 and VAL589). Likewise, remdesivir and niclosamide also possess MET124. Taken together, we might therefore hypothesize that MET124 plays a key role in the efficiency of these drugs targeting ACE2. MET24 appears to be a potential target for COVID-19. However, there is no similar amino acid for lopinavir, suggesting that further studies are needed to elucidate the molecular mechanism of lopinavir treatment of COVID-19.

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Biological, clinical and epidemiological features of COVID-19, SARS and MERS and AutoDock simulation of ACE2 - Infectious Diseases of Poverty - BioMed...