APR 13, 2021 8:00 AM PDT

The "Unexpected" Reason Why COVID Antivirals Don't Work

WRITTEN BY: Tara Fernandez

Purdue University researchers have made a breakthrough finding that could explain why the disease is so hard to manage therapeutically. In what was described as a surprising discovery, they found that a specific immune pathway activated in the lung tissue during COVID infection contributes to hyper-inflammation in severe cases, rendering standard antivirals ineffective.

Since the beginning of the pandemic, scientists have been scrambling to identify antiviral drugs to treat COVID patients with severe and life-threatening symptoms. Unfortunately, until now, this search has dug up very few viable options. Antivirals such as Remdesivir and Ruxolitinib are notoriously ineffective at treating COVID patients.

To understand why these drugs fall short, Purdue University computer science expert Majid Kazemian and colleagues took a closer look at the gene expression fingerprints left by SARS-CoV-2 infections. The team made the unexpected observation that small immune proteins, typically synthesized by the liver, were being produced in the fine structures of the lung known as alveoli. These proteins, part of the immune complement system, normally help the antibodies combat infectious pathogens.

“We observed that SARS-CoV2 infection of these lung cells causes expression of an activated complement system in an unprecedented way,” explained Kazemian. 

“This was completely unexpected to us because we were not thinking about activation of this system inside the cells, or at least not lung cells. We typically think of the complement source as the liver.”

However, instead of protecting against the coronavirus, complement activation in the lung triggers uncontrolled and detrimental tissue hyper-inflammation, a trademark symptom of severe COVID-19.

These findings provide evidence for why targeting inflammation outside the lungs has been disappointing so far. Instead, a more targeted approach that inhibits the expression and activation of complement proteins in lung cells could yield better results. For example, the researchers found that pairing Remdesivir with Ruxolitinib inhibited the complement response much more effectively than a monotherapy of the drugs independently, using an in vitro model of alveolar cells.

Despite the promising preliminary data, follow-up experiments are needed to determine whether such drug combos would work well in patients. 

 


Sources: Science Immunology, Purdue University.

About the Author
  • Tara Fernandez has a PhD in Cell Biology and has spent over a decade uncovering the molecular basis of diseases ranging from skin cancer to obesity and diabetes. She currently works on developing and marketing disruptive new technologies in the biotechnology industry. Her areas of interest include innovation in molecular diagnostics, cell therapies, and immunology. She actively participates in various science communication and public engagement initiatives to promote STEM in the community.
You May Also Like
JUL 15, 2021
Immunology
Your Immune System Can't Deal With All the Plastic You're Eating
JUL 15, 2021
Your Immune System Can't Deal With All the Plastic You're Eating
Microplastics—tiny fragments of plastic, less than five millimeters in diameter—pollute our environment and, ...
AUG 18, 2021
Cannabis Sciences
Cannabis Use Disorder Linked to COVID Hospitalization
AUG 18, 2021
Cannabis Use Disorder Linked to COVID Hospitalization
People with a genetic predisposition to cannabis use disorder (CUD) are more likely to require hospitalization after con ...
AUG 19, 2021
Cancer
Japanese Berry Vine Could Treat Lung Cancer
AUG 19, 2021
Japanese Berry Vine Could Treat Lung Cancer
A berry-producing vine in Japan has shown promise in mouse models for treating lung cancer. The corresponding study was ...
AUG 30, 2021
Cancer
A Hot Approach to CAR T Cells
AUG 30, 2021
A Hot Approach to CAR T Cells
Immunotherapy, a type of treatment that targets a patient’s immune system to enhance the natural ability to attack ...
OCT 05, 2021
Immunology
Monkey Gene Snares Viruses, Inspires Future Antivirals
OCT 05, 2021
Monkey Gene Snares Viruses, Inspires Future Antivirals
Many of the deadly viruses that affect humans—including Ebola and HIV—have animal origins. These infectious ...
OCT 18, 2021
Cancer
The History of Immunotherapy: Toxins, Targets & T Cells
OCT 18, 2021
The History of Immunotherapy: Toxins, Targets & T Cells
Cancer immunotherapy, a treatment that directly enhances a patient’s immune system, is typically perceived as a mo ...
Loading Comments...