Business Daily Media

Business Marketing

.

Hong Kong Baptist University-led research unveils cell entry mechanism of SARS-CoV-2 and therapeutic target for COVID-19

HONG KONG SAR - Media OutReach - 20 March 2023 - A study led by scientists from Hong Kong Baptist University (HKBU) has identified a protease called MT1-MMP that is a major host factor behind the infectivity of the SARS-CoV-2 virus in the human body, which leads to the infection of COVID-19 and multi-organ failure.

By applying a humanised antibody called 3A2 that can inhibit the activity of MT1-MMP, the viral load of infected mice was reduced by almost 90%. The research team also demonstrated that the protease is a potential therapeutic target for COVID-19.

Dr Xavier Wong Hoi-leong, Assistant Professor, and Dr Guo Xuanming, researcher of the Teaching and Research Division of the School of Chinese Medicine, introduce the research findings on the cell entry mechanism of SARS-CoV-2 and therapeutic target for COVID-19.
Dr Xavier Wong Hoi-leong, Assistant Professor, and Dr Guo Xuanming, researcher of the Teaching and Research Division of the School of Chinese Medicine, introduce the research findings on the cell entry mechanism of SARS-CoV-2 and therapeutic target for COVID-19.

The research findings have been published in the internationally renowned scientific journal Nature Communications.

ACE2 as a receptor for SARS-CoV-2 cell entry

Vaccination can protect people against COVID-19 and its potential complications, but it is not always effective in individuals with weak immune systems, or against some COVID-19 variants of concern. Thus, the development of a more effective treatment for COVID-19 remains a huge challenge in the post-vaccine era. Understanding the cell entry mechanism of SARS-CoV-2 is vital to curb the spread of the virus, and it will also aid the search for new COVID-19 treatments.

SARS-CoV-2 requires angiotensin-converting enzyme 2 (ACE2), a protein found on the membrane of human cells, as its receptor for cellular entry. Despite the lungs being the major organ affected by SARS-CoV-2 infection, only a small proportion of lung cells express ACE2.

Previous studies found that the infection of organs with low levels of ACE2 expression by SARS-CoV-2 is made possible by a soluble form of ACE2. The soluble ACE2 binds with SARS-CoV-2, carries the virus to cells with low levels of ACE2 expression, and facilitates its entry into the cells.

MT1-MMP mediates cell entry of SARS-CoV-2

A research team led by Dr Xavier Wong Hoi-leong, Assistant Professor of the Teaching and Research Division of the School of Chinese Medicine at HKBU, in collaboration with Dr Yuan Shuofeng, Assistant Professor of the Department of Microbiology at The University of Hong Kong, further studied how the physiological regulation of soluble ACE2 shedding contributes to the aetiology of COVID-19.

The team found that SARS-CoV-2 infection leads to the increased activation of MT1-MMP, a protease crucial for many physiological processes. MT1-MMP mediates the release of soluble ACE2 from ACE2-expressing cells. This soluble ACE2 in turn binds to the spike proteins of SARS-CoV-2 and carries it to the uninfected cells with low levels of ACE2 expression.

Notably, the team demonstrated that the introduction of human-soluble ACE2 enables SARS-CoV-2 to infect the lungs of a laboratory mouse strain (C57BL/6 mice) that is naturally insusceptible to SARS-CoV-2 infection due to the incompatibility of its mouse ACE2 and the viral spike proteins. The findings unveil the mechanism by which the virus hijacks host enzymes to enhance its infectivity, triggering multi-organ infections.

Antibody 3A2 blocks MT1-MMP activity

To study MT1-MMP's functions and how it affects viral infection, the researchers used human cells to create organoids, a 3D tissue structure grown in vitro to resemble and model different organs in the laboratory.

They discovered that blocking MT1-MMP activity with the monoclonal antibody 3A2 effectively depleted soluble ACE2 levels and reduced the degree of infection of SARS-CoV-2 in human lung, heart and liver organoids by 60-80%. Consistent results were obtained using the original strain of SARS-CoV-2, as well as variants of concern, such as Delta and Omicron. The results demonstrate that MT1-MMP is a major host factor that mediates the cell entry of SARS-CoV-2, and that it is also a potential therapeutic target for COVID-19 drugs.

The researchers further tested the effects of applying 3A2 in a mouse COVID-19 model. A group of 11 mice were treated with either 3A2 or vehicle controls. Older mice were used in the experiment as old age is a major risk factor for severe symptoms and mortality for COVID-19. The results show that 3A2 reduced the viral load of SARS-CoV-2 by almost 90% and dramatically alleviated lung tissue damage resulting from infection.

MT1-MMP as a therapeutic target

Dr Wong said: "Two major challenges when it comes to developing COVID-19 drugs are how to enhance treatment results for patients with weakened immune systems, and how to maintain the drugs' effectiveness across different viral strains. 3A2 has good potential to become an effective drug for curing COVID-19 because it antagonises the activity of MT1-MMP, instead of boosting the immunity of patients or acting directly on the virus.

"Our previous studies have demonstrated that 3A2 also offers protection against obesity and diabetes, two major risk factors for severe symptoms and mortality for COVID-19. Therefore, 3A2 could be particularly suitable for high-risk groups, including older adults and people with metabolic disorders. It could also be effective against emerging coronaviruses in the future, because ACE2 is a doorway for many such viruses with similar cell entry mechanisms. Further research and experiments on 3A2 are required before it can be applied in humans."

Hashtag: #HKBU

The issuer is solely responsible for the content of this announcement.

News from Asia

UD Trucks Celebrates 20 Years of Quon: A Legacy of People-First Innovation, Shaping The Future of Sustainable Logistics

SINGAPORE - Media OutReach Newswire - 10 June 2024 - UD Trucks celebrates the 20th anniversary of its flagship heavy-duty truck, Quon. In alignment with its "Better Life" purpose, UD Trucks remain...

Embrace Shopping Flexibility with Shopee’s Upgraded Change of Mind Policy: Easy & Fuss-Free 15-Day Free Returns, No Questions Asked*!

Shopee expands its Change of Mind policy to offer free returns on eligible items across all product categories within a 15-day guarantee period with no questions asked*, previously available only t...

Expereo Announces Appointment of Eric Wong as President of APAC

SINGAPORE - Media OutReach Newswire - 11 June 2024 - Expereo, the world's leading global intelligent internet company that connects people, places and things anywhere, today announces the appointm...

Jetstar Asia Highlights Exciting Family-Friendly Destinations for the June School Holidays

SINGAPORE - Media OutReach Newswire - 11 June 2024 - Jetstar Asia is excited to present a selection of family-friendly holiday destinations perfect for the June school holidays. From breathtaking...

Dive Into Summer With New Family Experiences At Nha Trang Marriott Resort & Spa, Hon Tre Island

Experience the Best of Vietnam’s Coastal Beauty NHA TRANG, VIETNAM - Media OutReach Newswire - 11 June 2024 - Marriott Bonvoy's largest hotel in Vietnam, the expansive Nha Trang Marriott Resort &...

G-AsiaPacific Wins Third AWS Partner of the Year Malaysia Award at AWS Partner Awards ASEAN 2024

Cloud Powerhouse G-AsiaPacific Clinches Third AWS Partner of the Year Malaysia Award SUBANG JAYA, MALAYSIA - Media OutReach Newswire - 11 June 2024 - G-AsiaPacific, a leading cloud service provid...

SHARP Revolutionises the Mobile Experience with the World’s Lightest 5G Smartphone and Heat-Releasing System for Prolonged Game Play

Experience Unmatched Features with the AQUOS R8s pro and AQUOS sense8 Smartphone SINGAPORE - Media OutReach Newswire - 11 June 2024 - SHARP, the renowned leader in consumer technology, is launch...

XTransfer and Banking Circle Announce Strategic Partnership

Collaboration Set to Boost Payment Capabilities for Importers/Exporters in Europe and the Middle East HONG KONG SAR - Media OutReach Newswire - 11 June 2024 - XTransfer, the World's Leading &...

London Square’s spectacular showcase at Rosewood Hong Kong provides a dazzling view of its UK new homes

HONG KONG SAR - Media OutReach Newswire - 11 June 2024 - Leading UK residential developer London Square, renowned for creating some of the most striking new homes in London, unveiled an exciting s...

OPPO Scores Unforgettable Experiences with Global Brand Ambassador Kaká at the UEFA Champions League Final 2024

LONDON, UNITED KINGDOM - Media OutReach Newswire – 1 June 2024 - The UEFA Champions League final kicked off today at London's legendary Wembley Stadium...

Popular

How to Implement a Well-Trained Sales Team

Technically, a sales force is not limited to simply all of the sales reps within a company's sales department. In reality, all company employees are salespeople, regardless of the department or position. If you work for the co...

How automating debt management could help your business stay afloat in 2024

With insolvencies on the rise, it pays to invest in technology that can help ensure you get paid. Another day, another business going belly-up and, more often than not, leaving its creditors whistling for their money or, if t...

How Thinking Inside The Box Helped Businesses Navigate The Pandemic

Businesses that have survived and thrived over the past 18 months have needed great adaptability, resourcefulness, imagination, and a slice of luck to be in a sector that can still operate. Importing and manufacturing have n...