The coronavirus disease 2019 (COVID-19) is caused by a novel RNA enveloped coronavirus, SARS-CoV-2 when the virus enters human airway cells via an ACE2-mediated entry process. This entry pathway is facilitated by the cell surface heparan sulfate proteoglycan (HSPG), which enhances viral attachment to the cell surface. Researchers at NIDDK and NCATS have discovered a collection of FDA-approved drugs that can interfere with the entry of SARS-CoV-2. These drugs can be grouped into three classes based on the distinct steps in the viral entry pathway that they target. Specifically, Mitoxantrone, Raloxifene, and Piceatannol bind to heparan sulfate; Sunitinib and BNTX target the actin cytoskeleton and Tilorone inhibits lysosomes. Strikingly, drugs targeting distinct entry steps can be combined in vitro to achieve a synergized anti-SARS-CoV-2 activity either against Spike-bearing pseudoviral particles or authentic SARS-CoV-2. Given that the safety of these drugs have been well documented in previous clinical studies, it is well positioned to advance these drugs to clinical studies to test their efficacy as a COVID-19 therapy.

Potential Commercial Applications: Competitive Advantages:
  • The technology would provide a low cost alternative therapy for COVID-19 patients. Given that the drugs are small molecules, they can easily reach the site of infection to inhibit viral entry and replication. The combination of Tilorone and Raloxifene can be conveniently given orally.
  • COVID-19 therapy


Yihong Ye (NIDDK)  ➽ more inventions...

Qi Zhang (NIDDK)  ➽ more inventions...

Wei Zheng (NCATS)  ➽ more inventions...

Catherine Chen (NCATS)  ➽ more inventions...

Intellectual Property:
US Pat: - issued -

Zhang, Q. et al.Heparan sulfate assists SARS-CoV-2 in cell entry and can be targeted by approved drugs in vitro. Cell Discov 6, 80 (2020)

Collaboration Opportunity:

The National Institute of Diabetes and Digestive and Kidney Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize COMBINATION THERAPIES FOR COVID-19. For collaboration opportunities, please contact: Dr. Yihong Ye at

Licensing Contact:
Betty Tong, Ph.D.
Phone: 301-451-7836

OTT Reference No: E-006-2021-0
Updated: Jan 25, 2021