Feinberg
Northwestern Medicine | Northwestern University | Faculty Profiles

News Center

  • Categories
    • Campus News
    • Disease Discoveries
    • Clinical Breakthroughs
    • Education News
    • Scientific Advances
  • Press Releases
  • Media Coverage
  • Podcasts
  • Editor’s Picks
    • COVID-19
    • Cardiology
    • Cancer
    • Neurology and Neuroscience
    • Aging and Longevity
    • Artificial Intelligence in Medicine
  • News Archives
  • About Us
    • Media Contact
    • Share Your News
    • News Feeds
    • Social Media
    • Contact Us
Menu
  • Categories
    • Campus News
    • Disease Discoveries
    • Clinical Breakthroughs
    • Education News
    • Scientific Advances
  • Press Releases
  • Media Coverage
  • Podcasts
  • Editor’s Picks
    • COVID-19
    • Cardiology
    • Cancer
    • Neurology and Neuroscience
    • Aging and Longevity
    • Artificial Intelligence in Medicine
  • News Archives
  • About Us
    • Media Contact
    • Share Your News
    • News Feeds
    • Social Media
    • Contact Us
Home » Study Shows Cell Membrane-Bound Enzyme is Essential for COVID-19 Infection
Disease Discoveries

Study Shows Cell Membrane-Bound Enzyme is Essential for COVID-19 Infection

By Melissa RohmanMay 26, 2022
Share
Facebook Twitter Email
Daniel Batlle, MD, the Earle, del Greco, Levin Professor of Nephrology/Hypertension, was lead author of the study published in Cell.

The membrane-bound form of angiotensin converting enzyme 2 (ACE2) is essential for enabling infection with SARS-CoV-2, the virus that causes COVID-19, according to a study published in the journal Cell.

There are two forms of ACE2 — a full-length form that can bind to the cell membrane of healthy host cells and a shorter, soluble form that circulates in the blood in small amounts. While both forms contain the same genetic sequence used by the receptor binding domain of the SARS-CoV-2 spike protein, soluble ACE2 lacks the ability to anchor to the cell membrane.

The current findings demonstrate that the full-length form is essential for SARS-CoV-2 infectivity while the soluble form does not promote infectivity, according to Daniel Batlle, MD, the Earle, del Greco, Levin Professor of Nephrology/Hypertension and lead author of the study.

“These findings are important to the COVID-19 field of promising therapies that involve soluble ACE2 proteins,” Batlle said. “They show that very low concentrations do not promote infectivity for SARS-CoV-2, whereas a high dose — which is the one targeted for the neutralization of SARS-CoV-2 — has the expected beneficial effect achieved by intercepting the viral spikes such that they cannot reach the membrane bound ACE2.”

Previous work from the Batlle laboratory and others have demonstrated that when soluble ACE2 proteins were administered in high doses to mice infected with SARS-CoV-2, viral replication was prevented and overall survival markedly improved.

However, other work has suggested that in a human kidney cell line, lower concentrations of soluble ACE2 may actually increase SARS-CoV-2 infectivity. This prompted a team of international investigators led by Batlle to perform further investigations using low concentrations of soluble ACE2 proteins.

In the current study, the team assessed viral infectivity by measuring RNA levels in the same human kidney cell line infected with SARS-CoV-2, which was exposed to very low concentrations of soluble ACE2. They also performed studies in human lung and kidney organoids infected with the SARS-CoV-2.

Overall, they found that lower concentrations of soluble ACE2 did not enhance SARS-CoV-2 infectivity in the kidney cell line or in the lung and kidney organoids. Additionally, using a new model of kidney organoids that lacked ACE2, the investigators discovered that SARS-CoV-2 infectivity is not possible in the absence of ACE2. This was the case for both low and high concentrations of soluble ACE2 which had no impact on SARS-CoV-2 infection, demonstrating that membrane bound ACE2 is the essential receptor for SARS-CoV-2 infection, according to Batlle.

“Soluble ACE2 at low concentrations are found in normal people and patients with COVID-19 and cardiovascular disease at risk for COVID-19 complications, therefore it is reassuring to know that soluble ACE2 cannot promote infectivity in humans,” Batlle said.

Jan Andrzej Wysocki, MD, PhD, research assistant professor of Medicine in the Division of Nephrology and Hypertension, and Luise Hassler, a research scholar in the Division of Nephrology and Hypertension, were co-authors of the study.

Other co-authors include Vasuretha Chandar, MS, and Robert Schwartz, MD, PhD, from Cornell University; Vanessa Monteil, PhD, and Ali Mirazimi, MD, PhD, from the Karolinska Institute in Sweden; Elena Garreta, PhD, and Nuria Montserrat, PhD, from The Institute for Bioengineering of Catalonia in Spain; Michael Bader, PhD,  from the Max Delbrück Center for Molecular Medicine in Berlin; and Josef Penninger, PhD, from the Department of Medical Genetics at the University of British Columbia in Vancouver, Canada.

This work was supported by a gift from the Joseph and Bessie Feinberg Foundation and National Institutes of Health grant R21AI166940-01.

COVID-19 Infectious Diseases Research
Share. Facebook Twitter Email

Related Posts

Pre-Surgery Immunotherapy May Increase Survival in Advanced Melanoma

Mar 23, 2023

Hormone Therapy Plus Current Treatments Improves Survival in Prostate Cancer

Mar 22, 2023

How ChatGPT Has, and Will Continue to, Transform Scientific Research

Mar 21, 2023

Comments are closed.

Latest News

Pre-Surgery Immunotherapy May Increase Survival in Advanced Melanoma

Mar 23, 2023

Hormone Therapy Plus Current Treatments Improves Survival in Prostate Cancer

Mar 22, 2023

How ChatGPT Has, and Will Continue to, Transform Scientific Research

Mar 21, 2023

New Directions for HIV Treatment

Mar 21, 2023

Humans are Not Just Big Mice: Identifying Science’s Muscle-Scaling Problem

Mar 20, 2023
  • News Center Home
  • Categories
  • Press Release
  • Media Coverage
  • Editor’s Picks
  • News Archives
  • About Us
Flickr Photos
20230317_NM336
20230317_NM626
20230317_NM662
20230317_NM655
20230317_NM642
20230317_NM643
20230317_NM624
20230317_NM303
20230317_NM551
20230317_NM559
20230317_NM536
20230317_NM508

Northwestern University logo

Northwestern University Feinberg School of Medicine

RSS Facebook Twitter LinkedIn Flickr YouTube Instagram
Copyright © 2023 Northwestern University
  • Contact Northwestern University
  • Disclaimer
  • Campus Emergency Information
  • Policy Statements

Type above and press Enter to search. Press Esc to cancel.