NHC Inhibits SARS-CoV-2 and other Coronaviruses in Human Respiratory Cells and Mice

Posted on by Jesse Santiano, M.D.

A ribonucleoside called NHC is a promising drug against COVID-19. It was studied by a collaboration of the University of North Carolina at Chapel Hill, Emory University, Vanderbilt University,  Drug Innovation Ventures at Emory (DRIVE), and the CDC. The study was published recently in  Science Translational Medicine.

In the study, NHC is in the form of EIDD-2801. EIDD-2801 has been effective in Venezuelan Equine Encephalitis, Influenza, Ebola, and other coronaviruses.

Within the past 20 years, the world has seen three strains of coronaviruses that have killed hundreds, and presently hundreds of thousands of people. From 2002-2003, Severe Acute Respiratory Syndrome or SARS was caused by the SARS coronavirus or SARS-CoV and killed 774. The Middle Eastern Severe Respiratory Syndrome or MERS was secondary to MERS-CoV in 2012 and caused 858 deaths.

Presently, COVID-19 caused by SARS-CoV-2 has killed 237 thousand and infected at least 3.3 million worldwide, according to the Johns Hopkins University of Medicine. SARS-CoV-2 is named as such because of its very close similarity to the SARS-CoV.

In this study, they infected mice and human respiratory epithelial cells with several types of coronaviruses, including the SARS-CoV, the MERS,-CoV, and the SARS-CoV-2. The human epithelial cells are the inside lining of the respiratory tract, here the SARS-CoV-2 starts the infection. The drug that they studied is the EIDD-2801.

EIDD stands for Emory Institute for Drug Development. EIDD-2801 is an orally bioavailable prodrug of the nucleoside NHC (β-D-N4–hydroxycytidine-5′-isopropyl ester). A prodrug is a substance that gets converted to a drug once metabolized by the body. The NHC works by causing a fatal mutation in the virus.

What the study showed is that EIDD-2801 can inhibit SARS-CoV-2 replication and treat COVID-19 if given early. The additional advantage is that it can be taken by mouth. That means patients with mild symptoms can stay at home and not need admission to the hospital for the medicine to be administered.

The following are the other results of their study. NHC is the active form of EIDD-2801.

  1. NHC prevents the replication of SARS, MERS-CoV, and SARS-CoV-2 in mice, thus preventing or lessening the severity of their diseases.
  2. NHC is antiviral against SARS-CoV, MERS-CoV, and SARS-CoV-2 in infected human epithelial cells. The antiviral activity was possible without causing toxic effects on the human cells.
  3. NHC is effective against remdesivir resistant animal coronaviruses.
  4. NHC decreased the lung hemorrhage and Acute Lung Injury in mice when given within 12 to 24 hours post-infection. In humans, this could mean that NHC can still be efficacious if taken within 7 to 10 days of infection.
  5. The mice who were given the NHC had better lung functions.
  6. NHC given before or 12 hours post-infection increased the viral mutation of MERS-CoV. Mutations in this situation made the viral particles non-infectious. This is consistent with the mechanism of action of EIDD-2801.

The next step for NHC is to start testing on monkeys and then human trials.

If NHC will be proven safe and effective for human use, this study shows that it can also be used for infections caused by future strains of coronaviruses.

Eidd-2801_Structure
Eidd-2801 Molecular Structure

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Reference:

An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice.
BY TIMOTHY P. SHEAHAN, AMY C. SIMS, SHUNTAI ZHOU, RACHEL L. GRAHAM, ANDREA J. PRUIJSSERS, MARIA L. AGOSTINI, SARAH R. LEIST, ALEXANDRA SCHÄFER, KENNETH H. DINNON III, LAURA J. STEVENS, JAMES D. CHAPPELL, XIAOTAO LU, TIA M. HUGHES, AMELIA S. GEORGE, COLLIN S. HILL, STEPHANIE A. MONTGOMERY, ARIANE J. BROWN, GREGORY R. BLUEMLING, MICHAEL G. NATCHUS, MANOHAR SAINDANE, ALEXANDER A. KOLYKHALOV, GEORGE PAINTER, JENNIFER HARCOURT, AZAIBI TAMIN, NATALIE J. THORNBURG, RONALD SWANSTROM, MARK R. DENISON, RALPH S. BARIC SCIENCE TRANSLATIONAL MEDICINE29 APR 2020

Image Credit: By Meodipt (talk) – Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=89559007

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