Mount Sinai identifies drugs that could prevent COVID-19 replication
Skip to main content
MDHC_Logotype_white
Subscribe
  • My Account
  • Login
  • Subscribe
  • News
    • This Week's News
    • COVID-19
    • Providers
    • Insurance
    • Government
    • Finance
    • Technology
    • Safety & Quality
    • People
    • Regional News
    • Digital Edition
    • Chip Kahn
      Q&A: Providing 'health security' should be top priority for Congress, Biden says FAH CEO Kahn
      The Check Up: Chip Kahn
      The Check Up: Chip Kahn of the Federation of American Hospitals
      'Little old West Virginia' sets pace on vaccine rollout
      Firefighter walking towards forest fire.
      Wildfires producing more harmful pollution
    • The Check Up: Chip Kahn
      The Check Up: Chip Kahn of the Federation of American Hospitals
      Chip Kahn
      Q&A: Providing 'health security' should be top priority for Congress, Biden says FAH CEO Kahn
      'Little old West Virginia' sets pace on vaccine rollout
      Dr. Bruce Siegel
      By protecting the healthcare safety net, Biden can put us on the path to a stronger country
    • The Check Up: Trenda Ray
      The Check Up: Trenda Ray of the University of Arkansas for Medical Sciences
      Trenda Ray
      Q&A: Arkansas nursing leader looking for creative staffing solutions as COVID cases surge
      Cook Lydia 4x6_i.jpg
      Northeast Ohio health systems increase community benefit values in 2019
      Vaccine rollout hits snag as health workers balk at shots
    • CMS approves rule forcing insurers to ease prior authorization
      COVID-19 still a big uncertainty for insurers in 2021
      Health insurers' outlook boosted after Dems' Georgia win
      humana_i.jpg
      Humana supports Ohio not-for-profits with $500,000
    • The Check Up: Chip Kahn
      The Check Up: Chip Kahn of the Federation of American Hospitals
      'Little old West Virginia' sets pace on vaccine rollout
      Joe Biden
      Revamp of the nation's vaccination effort may not be enough
    • Operation Warp Speed Dr. Moncef Slaoui, Pfizer Group President Angela Hwang, Moderna CEO Stephane Bancel, CVS Health Executive Vice President Karen Lynch and McKesson CEO Brian Tyler participate in a panel discussion on the COVID-19 vaccine.
      Hospitals, drug companies strive to stand out virtually at JPM
      Intermountain, Trinity, Memorial Hermann behind $300M private equity fund
      Operation Warp Speed to bump up McKesson's stock price
      Reporter's notebook: J.P. Morgan's 2021 health conference
    • A man in a room with servers.
      Momentum grows to outsource hospital tech functions in 2021
      5 things to know about Google's $2.1B Fitbit acquisition
      Providence bets on machine-learning, consolidating data centers
      Mental health treatment was most common telehealth service during COVID
    • Sticking to Mediterranean diet is good for the brain
      Chance of COVID-19 triage care looms over Arizona hospitals
      U.S. ramps up vaccinations to get doses to more Americans
      367146427.jpg
      Should businesses mandate that staff get the COVID vaccine?
    • Cone Health CEO, CFO to depart amid pending Sentara merger
      Tower Health's finance chief resigning after years of steep losses
      AHRQ director Gopal Khanna resigns in response to Capitol riot
      Brigham president stepping down after Moderna controversy
    • Midwest
    • Northeast
    • South
    • West
  • Insights
    • ACA 10 Years After
    • Best Practices
    • InDepth Special Reports
    • Innovations
    • The Affordable Care Act after 10 years
    • New care model helps primary-care practices treat obesity
      doctor with patient
      COVID-19 treatment protocol developed in the field helps patients recover
      Rachel Wyatt
      Project to curb pressure injuries in hospitals shows promise
      Yale New Haven's COVID-19 nurse-staffing model has long-term benefits
    • Michellene Davis
      Healthcare leadership lacks the racial diversity needed to reduce health disparities
      Dr. James Hildreth
      How medical education can help fight racism
      Modern Healthcare InDepth: Breaking the bias that impedes better healthcare
      Videos: Healthcare industry executives describe their encounters with racism
      Quotes from rebadged employees
      Outsourcing IT, revenue cycle takes toll on internal culture
    • A woman with a wearable sensor talking to her provider.
      Wearable sensors help diagnose heart rhythm problems in West Virginia
      self service station
      COVID-19 pushes patient expectations toward self-service
      Targeting high-risk cancer patients with genetics
      A nurse holds up a phone with a message to a family member saying surgery has started.
      Texting, tablets help hospitals keep family updated on patient care
  • Transformation
    • Patients
    • Operations
    • Care Delivery
    • Payment
    • Highmark Health inks six-year cloud, tech deal with Google
      Study: 1 in 5 patients report discrimination when getting healthcare
      HHS proposes changing HIPAA privacy rules
      Android health records app launches at 230 health systems
    • California hospitals prepare ethical protocol to prioritize lifesaving care
      Amazon, JPMorgan Chase, Berkshire Hathaway disband Haven
      Digital pathways poised to reshape healthcare continuum in 2021
      Healthcare was the hardest hit by supply shortages across all U.S. industries
    • A woman with a wearable sensor talking to her provider.
      Wearable sensors help diagnose heart rhythm problems in West Virginia
      New care model helps primary-care practices treat obesity
      How hospitals are building on COVID-19 telehealth momentum
      Researchers: Hospital price variation exacerbates health inequities
    • MedPAC votes to boost hospital payments, freeze or cut other providers
      Most Next Gen ACOs achieved bonuses in 2019
      Congress recalibrates Medicare Physician Fee Schedule after lobbying
      CMS approves rule to encourage value-based drug pricing
  • Data/Lists
    • Rankings/Lists
    • Interactive Databases
    • Data Points
    • Health Systems Financials
      Executive Compensation
      Physician Compensation
  • Op-Ed
    • Bold Moves
    • Breaking Bias
    • Commentaries
    • Letters
    • Vital Signs Blog
    • From the Editor
    • Wellstar CEO calls adapting for the pandemic her bold move
      Howard P. Kern
      Recognizing the value of telehealth in its infancy
      Dr. Stephen Markovich
      A bold move helped take him from family doctor to OhioHealth CEO
      Dr. Bruce Siegel
      Why taking a hospital not-for-profit was Dr. Bruce Siegel’s boldest move
    • Barry Ostrowsky
      Ending racism is a journey taken together; the starting point must be now
      Laura Lee Hall and Gary Puckrein
      Increased flu vaccination has never been more important for communities of color
      John Daniels Jr.
      Health equity: Making the journey from buzzword to reality
      Mark C. Clement and David Cook
      We all need to 'do something' to fight inequities and get healthcare right, for every patient, every time
    • Dr. Bruce Siegel
      By protecting the healthcare safety net, Biden can put us on the path to a stronger country
      Healing healthcare: some ideas for triage by the new Congress, administration
      Dr. Sachin H. Jain
      Medicare for All? The better route to universal coverage would be Medicare Advantage for All
      Connectivity: a social determinant of health that can exacerbate all the others
    • Letters: Eliminating bias in healthcare needs to be ‘deliberate and organic’
      Letters: Maybe dropping out of ACOs is a good thing for patients
      Letters: White House and Congress share blame for lack of national COVID strategy
      Letters: VA making strides to improve state veterans home inspections
    • Sponsored Content Provided By Optum
      How blockchain could ease frustration with the payment process
      Sponsored Content Provided By Optum
      Three steps to better data-sharing for payer and provider CIOs
      Sponsored Content Provided By Optum
      Reduce total cost of care: 6 reasons why providers and payers should tackle the challenge together
      Sponsored Content Provided By Optum
      Why CIOs went from back-office operators to mission-critical innovators
  • Awards
    • Award Programs
    • Nominate
    • Previous Award Programs
    • Other Award Programs
    • Best Places to Work in Healthcare Logo for Navigation
      Nominations Open - Best Places to Work in Healthcare
      Nominations Open - Health Care Hall of Fame
      Nominations Open - 50 Most Influential Clinical Executives
    • 100 Most Influential People
    • 50 Most Influential Clinical Executives
    • Best Places to Work in Healthcare
    • Health Care Hall of Fame
    • Healthcare Marketing Impact Awards
    • Top 25 Emerging Leaders
    • Top 25 Innovators
    • Top 25 Minority Leaders
    • Top 25 Women Leaders
    • Excellence in Nursing Awards
    • Design Awards
    • Top 25 COOs in Healthcare
    • 100 Top Hospitals
    • ACHE Awards
  • Events
    • Conferences
    • Galas
    • Webinars
    • COVID-19 Event Tracker
    • Leadership Symposium
    • Healthcare Transformation Summit
    • Women Leaders in Healthcare Conference
    • Workplace of the Future Conference
    • Strategic Marketing Conference
    • Social Determinants of Health Symposium
    • Best Places to Work Awards Gala
    • Health Care Hall of Fame Gala
    • Top 25 Minority Leaders Gala (2022)
    • Top 25 Women Leaders Gala
  • Listen
    • Podcast - Next Up
    • Podcast - Beyond the Byline
    • Sponsored Podcast - Healthcare Insider
    • Video Series - The Check Up
    • Sponsored Video Series - One on One
    • Carter Dredge
      Next Up Podcast: Ready, set, innovate! Innovation and disruption in healthcare
      Next Up Podcast: COVID-19, social determinants highlight health inequities — what next?
      Next Up Podcast: Saving Rural Health
      Ceci Connolly
      Next Up Podcast: How to navigate the murky post-election waters
    • An older man wearing a mask receiving a vaccine.
      Beyond the Byline: Verifying information on the chaotic COVID-19 vaccine rollout
      doctor burnout
      Beyond the Byline: How healthcare supply chain struggles contribute to employee burnout
      Beyond the Byline: Covering race and diversity in the healthcare industry
      Beyond the Byline: How telehealth utilization has impacted investor-owned company earnings
    • Leading intention promote diversity and inclusion
      Introducing Healthcare Insider Podcast
    • The Check Up: Chip Kahn
      The Check Up: Chip Kahn of the Federation of American Hospitals
      The Check Up: Trenda Ray
      The Check Up: Trenda Ray of the University of Arkansas for Medical Sciences
      The Check Up: Dr. Kenneth Davis
      The Check Up: Dr. Kenneth Davis of Mount Sinai Health System
      The Check Up: Dr. Thomas McGinn
      The Check Up: Dr. Thomas McGinn of CommonSpirit Health
    • Video: Ivana Naeymi Rad of Intelligent Medical Objects
  • MORE +
    • Advertise
    • Media Kit
    • Newsletters
    • Jobs
    • People on the Move
    • Reprints & Licensing
MENU
Breadcrumb
  1. Home
  2. Supply Chain
September 02, 2020 12:48 PM

Mount Sinai identifies drugs that could prevent COVID-19 replication

Neil Versel, Genomeweb
  • Tweet
  • Share
  • Share
  • Email
  • More
    Print
    Getty Images/iStockphoto
    Empty prescription medicine bottle on natural white surface.

    Researchers from the Icahn School of Medicine at Mount Sinai Health System in New York have developed a computational method to identify drugs that could be combat COVID-19. Unlike other research to repurpose drugs to treat infection, this effort focused on inhibiting viral uptake of SARS-CoV-2 in the first place.

    In a preprint paper posted to BioRxiv, the researchers explored viral sequences using PCR analysis, RNA sequencing, and bioinformatics. They identified four compounds that could block replication of the novel coronavirus, namely amlodipine, loperamide, terfenadine, and berbamine. They then validated these findings in multiple assays using primate Vero cells infected with SARS-CoV-2, A549 cells, and in human organoids.

    "These compounds were found to potently reduce viral load despite having no impact on viral entry or modulation of the host antiviral response in the absence of virus," according to the paper.

    "In the absence of a pan-specific coronavirus drug, or a SARS-CoV-2 vaccine, the next most useful tool would be the effective repurposing of FDA-approved drugs," the preprint said. "There is underutilized opportunity to understand the global molecular changes these drugs induce by using available sequencing data from diverse models and cell types."

    "You have a bunch of drugs that are blocking the virus in cell culture," said lead researcher Avi Ma'ayan, director of the Mount Sinai Center for Bioinformatics and principal investigator with the academic health system's LymeMIND team of other research into other potential COVID-19 treatments. "But this particular paper is showing a lot of details about why and which drug and … is beginning to understand the molecular mechanism."

    "We looked for those drugs that are really matching that signature. There are more drugs that fall into that cloud," Ma'ayan said.

    The researchers used a collection of gene expression profiles from the National Institutes of Health's Library of Integrated Network-based Cellular Signatures (LINCS) database that has previously been applied to identify drugs that attenuate the Ebola virus. With SARS-CoV-2, the Mount Sinai team was able to spot transcriptional irregularities by comparing changes in gene expression before and after infection or drug treatment.

    In this new work, the Mount Sinai team studied 50 genes that were downregulated by the virus or 50 upregulated by certain drugs. They also looked at the 100 genes most commonly coexpressed by ACE2, known to be the receptor of SARS-CoV-2. This methodology also led the researchers to quercetin, an effector of these ACE2-coexpressed genes.

    The research on ACE2 expression was more of a negative control, according to Ma'ayan. "We did look for drugs that can reduce the level of the expression of the receptor and we found a drug that had a high score, but it actually made things worse," he said. "When you test it with the virus, you actually get more viral replication and more virus when you use that drug."

    Manual examination of drugs revealed that terfenadine, loperamide, berbamine, trifluoperazine, amlodipine, RS-504393, and chlorpromazine regularly targeted this expression space.

    The antidiarrheal loperamide is widely available over the counter. Terfenadrine is an antihistamine, sold as Seldane in the U.S., that was pulled from the market in the 1990s after it was linked to cardiac arrhythmia.

    While SARS-CoV-2 appears to prevent antiviral response by masking aberrant RNA, replication of the virus still produces a unique transcriptional footprint, they said, citing a May paper in Cell from Daniel Blanco-Melo, a postdoctoral researcher in Mount Sinai's tenOever Laboratory.

    The Ma'ayan work builds on this by attempting to identify drugs that might invert transcriptional signatures to inhibit replication. The tenOever Lab assisted on this new experiment, and Benjamin tenOever, director of Mount Sinai's Virus Engineering Center for Therapeutics and Research (VECToR), is listed as an author on the preprint.

    The findings, or "predictions," as Ma'ayan called them, were validated with multiple assays and multiple cell lines. Ma'ayan's lab built the computational model, but tenOever's lab tested the hypotheses about drugs that the model predicted. Ma'ayan said that some predictions were based on earlier work by tenOever's team.

    According to Ma'ayan, seven of the eight drugs initially tested completely blocked transmission in monkey Vero cells. Some also worked in human cells.

    The prepress paper only mentioned the genetic signatures from the Cell paper, but Ma'ayan said that he and his colleagues looked at signatures from other viruses and compounds, including the controversial hydroxychloroquine, in an effort to determine if that might inhibit SARS-CoV-2 replication.

    Ma'ayan said that hydroxychloroquine does work similarly to the drugs his Mount Sinai tested, but requires a much higher concentration than the others. It also has more side effects, so he said that loperamide and amlodipine are likely to be more effective than hydroxychloroquine.

    After the prepress article was posted, the researchers found several other published studies that have data from cells infected with the coronavirus, so they now are trying to see if there is a consensus on the drug and pathway predictions. "That we think is critical. We are creating a more comprehensive across-lab analysis," Ma'ayan said.

    They are using machine learning to look for common themes among published "hits," according to Ma'ayan. "A lot of people are publishing drugs that are working in cells, but we're trying to synthesize all that information and try to make sense of it, and also explain the mechanisms behind those observations," he said.

    Ma'Ayan said that his goal is to get these compounds into human clinical trials, whether at Mount Sinai or elsewhere. He also wants to study combination therapies.

    Christina Fliege technical research lead at the NCSA Genomics in the National Center for Supercomputing Applications at the University of Illinois at Urbana-Champaign, said it was important not to "overinterpret" the results because the work involved Gene Ontology analysis. "Gene ontology ... analysis, in general just gives a hint of further experiments," Fliege said.

    "That's a problem because the number of genes they're using for Gene Ontology as an input is quite small, which means that whatever you miss will have a big impact on the statistical results," Mainzer added.

    Liudmila Mainzer, a technical program manager at NCSA Genomics said that reviewers and others who might consider adopting the methodology or running trials with the identified compounds will want to pay attention to the inputs in this experiment in order to validate the findings.

    "Right now, it's very difficult for us to make that interpretation because we don't know the versions of the software they used for annotation and the number of genes they used was very small, so there can be some room for possible misinterpretation," Mainzer cautioned.

    However, Mainzer said that the researchers accomplished their main objective of matching gene expression patterns in response to SARS-CoV-2 with the inverse of patterns related to drug response. "As they can make that match, ultimately, it doesn't matter exactly what the Gene Ontology database says because you're not diving into the biological underpinnings of these processes," she said.

    "The ultimate validation is, if you apply this drug, does it work? Does it prevent COVID from reproducing?" Mainzer said. "They did the match, they found the drugs, and then they applied them to the cells."

    This story first appeared in our sister publication, Genomeweb.

    Letter
    to the
    Editor

    Send us a letter

    Have an opinion about this story? Click here to submit a Letter to the Editor, and we may publish it in print.

    Recommended for You
    Expanded vaccine rollout in U.S. spawns a new set of problems
    Expanded vaccine rollout in U.S. spawns a new set of problems
    U.S. on track for herd immunity by summer
    U.S. on track for herd immunity by summer
    Sponsored Content
    Get Free Newsletters

    Sign up for free enewsletters and alerts to receive breaking news and in-depth coverage of healthcare events and trends, as they happen, right to your inbox.

    Subscribe Today

    The weekly magazine, websites, research and databases provide a powerful and all-encompassing industry presence. We help you make informed business decisions and lead your organizations to success.

    Subscribe
    Connect with Us
    • LinkedIn
    • Twitter
    • Facebook
    • RSS
    • Instagram

    Stay Connected

    Join the conversation with Modern Healthcare through our social media pages

    MDHC_Logotype_white
    Contact Us

    (877) 812-1581

    Email us

     

    Resources
    • Contact Us
    • Advertise with Us
    • Ad Choices Ad Choices
    • Sitemap
    Editorial Dept
    • Submission Guidelines
    • Code of Ethics
    • Awards
    • About Us
    Legal
    • Terms and Conditions
    • Privacy Policy
    • Privacy Request
    Modern Healthcare
    Copyright © 1996-2021. Crain Communications, Inc. All Rights Reserved.
    • News
      • This Week's News
      • COVID-19
      • Providers
      • Insurance
      • Government
      • Finance
      • Technology
      • Safety & Quality
      • People
      • Regional News
        • Midwest
        • Northeast
        • South
        • West
      • Digital Edition
    • Insights
      • ACA 10 Years After
      • Best Practices
      • InDepth Special Reports
      • Innovations
    • Transformation
      • Patients
      • Operations
      • Care Delivery
      • Payment
    • Data/Lists
      • Rankings/Lists
      • Interactive Databases
      • Data Points
    • Op-Ed
      • Bold Moves
      • Breaking Bias
      • Commentaries
      • Letters
      • Vital Signs Blog
      • From the Editor
    • Awards
      • Award Programs
        • 100 Most Influential People
        • 50 Most Influential Clinical Executives
        • Best Places to Work in Healthcare
        • Health Care Hall of Fame
        • Healthcare Marketing Impact Awards
        • Top 25 Emerging Leaders
        • Top 25 Innovators
        • Top 25 Minority Leaders
        • Top 25 Women Leaders
      • Nominate
      • Previous Award Programs
        • Excellence in Nursing Awards
        • Design Awards
        • Top 25 COOs in Healthcare
      • Other Award Programs
        • 100 Top Hospitals
        • ACHE Awards
    • Events
      • Conferences
        • Leadership Symposium
        • Healthcare Transformation Summit
        • Women Leaders in Healthcare Conference
        • Workplace of the Future Conference
        • Strategic Marketing Conference
        • Social Determinants of Health Symposium
      • Galas
        • Best Places to Work Awards Gala
        • Health Care Hall of Fame Gala
        • Top 25 Minority Leaders Gala (2022)
        • Top 25 Women Leaders Gala
      • Webinars
      • COVID-19 Event Tracker
    • Listen
      • Podcast - Next Up
      • Podcast - Beyond the Byline
      • Sponsored Podcast - Healthcare Insider
      • Video Series - The Check Up
      • Sponsored Video Series - One on One
    • MORE +
      • Advertise
      • Media Kit
      • Newsletters
      • Jobs
      • People on the Move
      • Reprints & Licensing