Feinberg
Northwestern Medicine | Northwestern University | Faculty Profiles

News Center

  • Categories
    • Campus News
    • Disease Discoveries
    • Clinical Breakthroughs
    • Education News
    • Scientific Advances
  • Press Release
  • 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 Release
  • 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 Explores Possible Therapeutic Target for SARS-CoV-2
Disease Discoveries

Study Explores Possible Therapeutic Target for SARS-CoV-2

By Melissa RohmanJun 24, 2021
Share
Facebook Twitter Email
Ludmilla Shuvalova, PhD, research associate professor of Microbiology-Immunology, was a co-author of the study published in PNAS.

Inhibiting a specific protein complex in SARS-CoV-2, the virus that causes COVID-19, may be a promising therapeutic target for treating the disease, according to a Northwestern Medicine study published in Proceedings of the National Academy of Sciences (PNAS).

Similar to other RNA viruses, the genome of the SARS-CoV-2 contains a “capping” modification which stabilizes and improves viral translation as well as protects the virus from degradation by the host’s immune system and allows it to proliferate.

“The virus developed the defense mechanism by capping the freshly made RNA inside the host cell allowing it to avoid host anti-viral defenses and giving it time to multiply,” said Ludmilla Shuvalova, PhD, research associate professor of Microbiology-Immunology and a co-author of the study.

Previous work has found that this capping is performed by viral proteins that assemble into a large replication-transcription complex. The final step of this multistep process is completed by two protein complexes, Nsp10/14 and Nsp10/16, with Nsp10/16 — an RNA methyltransferase comprised of two proteins bound together — specifically responsible for critical methyltransferase activity.

Andrzej Joachimiak, PhD, adjunct professor of Microbiology-Immunology and co-director of the Center for Structural Genomics of Infectious Diseases, was senior author of the study.

For the current study, the investigators studied the exact conformational changes of the Nsp10/16 complex during methyltransferase activity in SARS-CoV-2-infected cells using synchrotron serial crystallography.

The team determined that inhibiting this complex and its capping ability may reduce viral proliferation, potentially serving as a drug target for treating COVID-19.

“Considering that capping of viral RNA is vital for the virus, finding the inhibitors or potential drugs of this reaction could be very beneficial in fight against COVID-19. If a drug can be developed to inhibit Nsp10/16, the immune system should be able to detect the virus and eradicate it faster,” Shuvalova said.

Andrzej Joachimiak, PhD, adjunct professor of Microbiology-Immunology and co-director of the Center for Structural Genomics of Infectious Diseases, was senior author of the study.

Additional co-authors of the study include George Minasov, PhD, research associate professor of Microbiology-Immunology, and Karla Satchell, PhD, professor of Microbiology-Immunology, co-director of the Center for Structural Genomics of Infectious Diseases and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

The active site of nsp16 with the Cap-1 analog and S-Adenosyl-L-Homocysteine (SAH), products of the methyl transfer reaction. Atoms include the following: oxygen (red), nitrogen (blue), phosphorous (orange), sulfur (gold), carbon (cyan), the Cap-1 analog (yellow) and SAH (green). The electron density map surrounding the Cap-1 is shown as a mesh in red and for SAH in purple.

In a recent follow-up paper published in Science Signaling, the investigators identified another novel therapeutic target — a coronavirus-specific pocket in the protein Nsp16, that binds the virus-genomic fragment which is used by the coronavirus as the template for the viral building block. Developing a drug to fit this unique pocket and block the function of the Nsp16 protein may be another promising therapeutic strategy, according to the authors.

The current study was supported by, the National Institute of Allergy and Infectious Diseases, the Department of Health and Human Services, under Contract HHSN272201700060C, and the Department of Energy (DOE) Office of Science through the National Virtual Biotechnology Laboratory, a consortium of DOE national laboratories focused on response to COVID-19, with funding provided by the CARES Act.

COVID-19 Immunology Microbiology Research
Share. Facebook Twitter Email

Related Posts

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

Mar 20, 2023

Predicting Risk of Blood Clots in Brain Tumors

Mar 16, 2023

Understanding How Exercise Induces Systemic Metabolic Benefits

Mar 15, 2023

Comments are closed.

Latest News

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

Mar 20, 2023

AOA Honors New Members

Mar 20, 2023

Celebrating Feinberg’s 2023 Match Day

Mar 17, 2023

Predicting Risk of Blood Clots in Brain Tumors

Mar 16, 2023

Understanding How Exercise Induces Systemic Metabolic Benefits

Mar 15, 2023
  • News Center Home
  • Categories
  • Press Release
  • Media Coverage
  • Editor’s Picks
  • News Archives
  • About Us
Flickr Photos
_5NM1245
230204_SERIO_MANDELL_Feinberg_Formal_0928
_5NM1715
_5NM0526
_5NM1026 (1)
_5NM1906
_5NM2173
230204_SERIO_MANDELL_Feinberg_Formal_0896
230204_SERIO_MANDELL_Feinberg_Formal_1113
230204_SERIO_MANDELL_Feinberg_Formal_1868
230204_SERIO_MANDELL_Feinberg_Formal_1237
230204_SERIO_MANDELL_Feinberg_Formal_1172

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.