Skip to main content
NIH Intramural Research Program, Our Research Changes Lives

Navigation controls

  • Search
  • Menu

Social follow links

  • Podcast
  • Instagram
  • Twitter
  • YouTube
  • LinkedIn

Main navigation

  • About Us
    • What Is the IRP?
    • History
    • Honors
      • Nobel Prize
      • Lasker Award
      • Breakthrough Prize
      • Presidential Early Career Award for Scientists and Engineers (PECASE)
      • Presidential Medal of Freedom
      • National Medal of Science
      • Searle Scholars
      • The National Academy of Sciences
      • The National Academy of Medicine
      • The National Academy of Engineering
      • The American Academy of Arts and Sciences
      • National Medal of Technology & Innovation
      • Samuel J. Heyman Service to America Medals
      • Crafoord Prize
      • Fellows of the Royal Society
      • Canada Gairdner Awards
    • Organization & Leadership
    • Our Programs
      • NCI
      • NEI
      • NHGRI
      • NHLBI
      • NIA
      • NIAAA
      • NIAID
      • NIAMS
      • NIBIB
      • NICHD
      • NIDA
      • NIDCD
      • NIDCR
      • NIDDK
      • NIEHS
      • NIMH
      • NIMHD
      • NINDS
      • NINR
      • NLM
      • CC
      • NCATS
      • NCCIH
    • Research Campus Locations
    • Contact Information
  • Our Research
    • Scientific Focus Areas
      • Biomedical Engineering & Biophysics
      • Cancer Biology
      • Cell Biology
      • Chemical Biology
      • Chromosome Biology
      • Clinical Research
      • Computational Biology
      • Developmental Biology
      • Epidemiology
      • Genetics & Genomics
      • Health Disparities
      • Immunology
      • Microbiology & Infectious Diseases
      • Molecular Biology & Biochemistry
      • Molecular Pharmacology
      • Neuroscience
      • RNA Biology
      • Social & Behavioral Sciences
      • Stem Cell Biology
      • Structural Biology
      • Systems Biology
      • Virology
    • Principal Investigators
      • View by Investigator Name
      • View by Scientific Focus Area
    • Accomplishments
      • View All Accomplishments by Date
      • View All Health Topics
      • The Body
      • Health & Wellness
      • Conditions & Diseases
      • Procedures
    • Accelerating Science
      • Investing in Cutting-Edge Animal Models
      • Creating Cell-Based Therapies
      • Advancing Computational and Structural Biology
      • Combating Drug Resistance
      • Developing Novel Imaging Techniques
      • Charting the Pathways of Inflammation
      • Zooming in on the Microbiome
      • Uncovering New Opportunities for Natural Products
      • Stimulating Neuroscience Research
      • Pursuing Precision Medicine
      • Unlocking the Potential of RNA Biology and Therapeutics
      • Producing Novel Vaccines
    • Research in Action
      • View All Stories
      • Too Much of a Good Thing
      • Turning Face Perception on Its Head
      • Safeguarding a Second Chance at Life
      • A Biological Betrayal
    • Trans-IRP Research Resources
      • Supercomputing
    • IRP Review Process
    • Commercializing Inventions
  • NIH Clinical Center
    • Clinical Center Facilities
    • Advancing Translational Science
    • Clinical Trials
      • Get Involved with Clinical Research
      • Physician Resources
  • News & Events
    • In the News
    • I am Intramural Blog
    • Speaking of Science Podcast
    • SciBites Video Shorts
    • The NIH Catalyst Newsletter
    • Events
  • Careers
    • Faculty-Level Scientific Careers
    • Trans-NIH Scientific Recruitments
      • Stadtman Tenure-Track Investigators
        • Science, the Stadtman Way
        • Earl Stadtman Investigator Frequently Asked Questions
      • Lasker Clinical Research Scholars
      • Independent Research Scholar
    • Scientific & Clinical Careers
    • Administrative Careers
  • Research Training
    • Program Information
    • Training Opportunities
    • NIH Work/Life Resources
The NIH Catalyst: A Publication About NIH Intramural Research

National Institutes of Health • Office of the Director | Volume 29 Issue 2 • March–April 2021

From the Deputy Director for Intramural Research

How the NIH Intramural Program Is Fighting the COVID-19 Pandemic

BY MICHAEL M. GOTTESMAN, DDIR

Michael Gottesman

Given the constant presence of NIH leaders such as NIH Director Francis Collins and National Institute of Allergy and Infectious Diseases (NIAID) Director Anthony Fauci in the popular press, on TV and radio and in print, and in commentaries in academic journals, it is clear that the NIH has played a major role in strategic planning, communication of public-health requirements, and development of strategies to prevent, detect, and treat infection caused by severe acute respiratory syndrome virus 2 (SARS-CoV-2), the virus responsible for COVID-19. What may not be as clear to many intramural staff are the major contributions that have been made over the past year by intramural—and extramural—scientists, working in teams and as independent contributors, to the science underlying our current understanding of the diagnosis, prevention, therapy, and pathophysiology of COVID-19.

Early in the COVID-19 pandemic, we sought to document the contributions of our intramural scientists to the antipandemic effort by creating a dashboard in collaboration with Christine Cutillo (National Center for Advancing Translational Sciences, NCATS) listing all of the projects being carried out in the intramural research program (IRP). Currently, there are 23 institutes and centers involved in COVID research with about 400 active projects—ranging from basic science to preclinical research to clinical trials—and 313 distinct PIs. The research areas are equally divided between immunology–host response and therapeutic (drugs and biologics) at 14%; 10% in pathogenesis; 8% in genetics and genomics; and 7% in structural biology. Bioinformatics, virology, computational and systems biology, diagnostics, epidemiology, and vaccines are all in the 6% range. Natural history, clinical trial, and mental and behavioral health are in the 2–5% range. There are 63 reagents available in the registry. When the IRP dashboard was being developed, a resource center collating NIH COVID-19 related resources and tools was also created to enhance sharing and coordination; both the dashboard and the resource center can be accessed via the NCATS COVID-19 Resource Center (NIH PIV card required).

Many of these research activities were highlighted in the October 29–30, 2021, workshop organized by the NIH COVID-19 Scientific Interest Group (chaired by Pam Schwartzberg, NIAID) and colleagues at the FDA. In addition, the Office of Intramural Research, with funding by NIAID, provided grant support for intramural scientists as part of the Intramural Targeted Anti-COVID-19, a competition overseen by Ted Pierson in NIAID. Of 159 applications, 40 were funded.

There have been so many important intramural contributions to the COVID-19 effort that it is difficult to choose just a few to highlight in this essay, but I will do my best (and I hope that the architects of the equally important work that is not cited do not feel slighted).

The most obvious is the contribution of the dedicated team at NIAID’s Vaccine Research Center (VRC) to the development of a structure-based vaccine. Since the SARS outbreak in 2002–2004, VRC Deputy Director Barney Graham and his many talented associates and colleagues, including Kizzmekia Corbett, (NIAID), have been working on the general principles for creating vaccines to counteract significant coronavirus epidemics. Targeting the coronavirus spike (S) protein, they discovered (with their collaborator Jason McLellan, an alumnus of the VRC and now at the University of Texas at Austin), that substitutions of two prolines between two key areas would stabilize the S protein in its native functional conformation. This engineered structure has become the basis for many of the vaccines under current development, all of which have proven to be exceptionally effective in preventing SARS-CoV-2 symptomatic infections. Specifically, this variant is encoded by the messenger RNA present in the Pfizer and Moderna vaccines. It is also encoded by the adenovirus type 26 vaccine vector in the Johnson and Johnson–Janssen vaccine.

In the area of therapeutics, NCATS has done extensive work to screen existing drugs to be repurposed for treatment of SARS-CoV-2 infection. In addition, the team of Emmie de Wit and Vincent Munster at NIAID’s Rocky Mountain Laboratories (Hamilton, Montana) was one of the first to demonstrate the efficacy of the antiviral agent remdesivir in rodents and nonhuman primates. Their work accelerated the development of this agent for treatment of hospitalized patients with moderate to severe COVID-19; remdesivir remains a standard of care.

There have been many contributions to understanding the structure of the virus and how it enters and leaves cells. In addition to the pioneering and elegant structural work from the Graham group, NIH structural biologists throughout the IRP have explored the structure of the S protein–angiotensin-converting enzyme 2 receptor complex, providing a much better understanding of the early steps in viral entry.

Also relevant to viral entry, the team led by Kelly Ten Hagen (National Institute of Dental and Craniofacial Research) showed that furin cleavage in SARS-CoV-2 is modulated by mucin type O glycosylation, which possibly explains why the UK B.1.1.7 variant is more transmissible than the other variants, because some of the mutations in this variant are close to this site. At the other end of the viral replication cycle, Nihal Altan-Bonnet (National Heart, Lung, and Blood Institute) demonstrated that SARS-CoV-2 uses a lysosomal pathway to leave cells, an unexpected finding that could have important therapeutic implications.

Considerable progress has also been made in understanding what host factors predispose someone to severe disease. Helen Su and Luigi Notarangelo, NIAID, in collaboration with the laboratory of Jean-Laurent Casanova at Rockefeller University (New York), showed that in up to 15% of persons severely ill with COVID-19, defects in the pathways involved in the action of type 1 interferons (interferons alpha and omega), caused either by mutations or neutralizing autoantibodies, played a significant role. This work reinforces the role that even subtle defects in the immune system play in susceptibility to severe viral infection and may lead to potential therapies for severely ill patients who have such defects.

Although these examples don’t begin to touch the tip of the coronavirus iceberg at NIH, I think they are pretty “cool” science. We can expect much more to come.

This page was last updated on Tuesday, February 15, 2022

  • Issue Overview
  • Features
    • The 1918 Flu and COVID-19: A Tale of Two Pandemics
    • Introducing NIH’s Newest Lasker Scholars
    • Stadtman Investigators Pursuing Their Passion for Science
    • Fueling the Next Genomic Revolution
    • COVID-19 Timeline at NIH (JANUARY-FEBRUARY 2021)
  • Departments
    • From the Deputy Director for Intramural Research
    • From the Annals of NIH History
    • From the Annals of NIH History: Lefkowitz
    • Research Briefs
    • Research Briefs: Maternal Morbidity and Mortality
    • Research Briefs: Kidney Disease
    • The Training Page
    • Announcements: Kudos to Dan Kastner
    • Photographic Moment
    • Announcements
  • Issue Contents
  • Download this issue as a PDF

Catalyst menu

  • Current Issue
  • Previous Issues
  • About The NIH Catalyst
  • Contact The NIH Catalyst
  • Share Your Story
  • NIH Abbreviations

Catalyst links

  • Follow The NIH Catalyst

Subscribe Today!

Subscribe to The NIH Catalyst Newsletter and receive email updates.

Subscribe

Get IRP Updates

Subscribe

  • Email
  • Print
  • Share Twitter Facebook LinkedIn

Main navigation

  • About Us
    • What Is the IRP?
    • History
    • Honors
    • Organization & Leadership
    • Our Programs
    • Research Campus Locations
    • Contact Information
  • Our Research
    • Scientific Focus Areas
    • Principal Investigators
    • Accomplishments
    • Accelerating Science
    • Research in Action
    • Trans-IRP Research Resources
    • IRP Review Process
    • Commercializing Inventions
  • NIH Clinical Center
    • Clinical Center Facilities
    • Advancing Translational Science
    • Clinical Trials
  • News & Events
    • In the News
    • I am Intramural Blog
    • Speaking of Science Podcast
    • SciBites Video Shorts
    • The NIH Catalyst Newsletter
    • Events
  • Careers
    • Faculty-Level Scientific Careers
    • Trans-NIH Scientific Recruitments
    • Scientific & Clinical Careers
    • Administrative Careers
  • Research Training
    • Program Information
    • Training Opportunities
    • NIH Work/Life Resources
  • Department of Health and Human Services
  • National Institutes of Health
  • USA.gov

Footer

  • Home
  • Contact Us
  • IRP Brand Materials
  • HHS Vulnerability Disclosure
  • Web Policies & Notices
  • Site Map
  • Search