Studies Identify Weak Spots In SARS-CoV-2 Virus

sars-cov-2 cells on red background

Jasmin Merdan / Getty Images

Key Takeaways

  • New studies identify 128 molecular targets that could be targeted to stop coronaviruses from spreading to other cells.
  • The transmembrane protein 41 B is also linked with aiding the viral replication of the Zika virus.
  • Deactivating this protein may be potentially useful for antiviral therapies.

While a COVID-19 vaccine is being hailed as the light at the end of the pandemic, a team of researchers from NYU is prepping for a plan B. The results from two of their studies published in the journal Cell show that inhibiting specific proteins can prevent the SARS-CoV-2 virus from replicating and ultimately causing COVID-19 infections.

How Does SARS-CoV-2 Cause Infection?

A virus needs to transfer its genetic information to a host cell in order to replicate. Eric J. Yager, PhD, an associate professor of microbiology for the Albany College of Pharmacy and Health Sciences and the Center for Biopharmaceutical Education and Training, says that viruses lack the machinery to make their own proteins and reproduce. As a result, hijacking cells are necessary for their survival.

SARS-CoV-2 uses a spike protein to bind with the ACE2 receptor found on the surface of human cells. The spike protein acts as a key that latches on to the ACE2 receptor. This allows for viral entry into the cell.

To ensure the hijacking is a success, Yager says that SARS-CoV-2 manipulates the protective layer of fat surrounding the cell.

“Cellular membranes are comprised of a variety of lipid molecules,” Yager, who was not involved with the pair of Cell studies, tells Verywell. “Accordingly, scientists have found that several clinically relevant viruses are able to alter host cell lipid metabolism in order to create an environment favorable for the assembly and release of infectious viral particles.”

Once inside, the virus can force the cell to make more copies of it. “Viruses co-opt host cell machinery and biosynthetic pathways for genome replication and the production of viral progeny,” Yager says.

To prevent COVID-19 infection, researchers need to stop the virus from entering the cells.

Ongoing coronavirus research has focused on blocking the spike protein. In fact, the COVID-19 mRNA vaccines developed by Pfizer/BioNTech and Moderna work by giving cells a nonpermanent set of instructions to temporarily create the virus’s spike protein. The immune system recognizes the spike protein as a foreign invader and quickly destroys it. However, the experience allows the immune system to make a memory of those instructions. So, if the real virus does ever enter your body, your immune system has prepared defenses to fight against it.

While the spike protein may be a good target, the researchers of the Cell study suggest that it might not be the only one.

“An important first step in confronting a new contagion like COVID-19 is to map the molecular landscape to see what possible targets you have to fight it,” says John T. Poirier, PhD, an assistant professor of medicine at NYU Langone Health and co-author of the two studies in a recent press release. “Comparing a newly-discovered virus to other known viruses can reveal shared liabilities, which we hope serve as a catalogue of potential vulnerabilities for future outbreaks.”

Investigating Other Potential Targets

The researchers sought to find the molecular components of human cells that SARS-CoV-2 takes over in order to copy itself. They used CRISPR-Cas9 to inactivate a single gene in a human cell. In total, they turned off the function of 19,000 genes. After, the cells were exposed to SARS-CoV-2 and three other coronaviruses known to cause the common cold.

Due to viral infection, many cells died. The cells that did live were able to survive because of the inactivated gene, which the authors suggest must be crucial for replication.

In total, the researchers found 127 molecular pathways and proteins that the four coronaviruses needed to copy themselves successfully.

In addition to the 127 identified, the researchers decided to focus on a protein called transmembrane protein 41 B (TMEM41B).

Their decision was based on information from a 2016 study showing that TMEM41B was crucial for replication of the Zika virus. While this protein’s role is to clear out cellular waste by wrapping it in a coating of fats, the researchers suggest coronaviruses may be able to use this fat as a sort of hiding place.

What This Means For You

While we wait for a publicly-available vaccine, researchers are continuing to develop COVID-19 treatments. By targeting TMEM41B, scientists may be able to create antiviral therapies that focus on preventing severe illness by stopping the coronavirus from spreading to the rest of the body.

Targeting Proteins for Drug Development

Targeting viral proteins is not a novel strategy, Yager says. It also works in treating bacterial infections.

“Antibiotics such as doxycycline, streptomycin, and erythromycin interfere with the ability of the bacterial 70S ribosome to synthesize bacterial proteins,” Yager says. “Antibiotics such as rifampicin work to inhibit the synthesis of bacterial mRNA, which is used as a blueprint to synthesize bacterial proteins.”

The researchers believe that TMEM41B and other proteins could be potential targets for future therapies.

“Together, our studies represent the first evidence of transmembrane protein 41 B as a critical factor for infection by flaviviruses and, remarkably, for coronaviruses, such as SARS-CoV-2, as well,” Poirier said in a press release. “While inhibiting transmembrane protein 41 B is currently a top contender for future therapies to stop coronavirus infection, our results identified over a hundred other proteins that could also be investigated as potential drug targets.”

The information in this article is current as of the date listed, which means newer information may be available when you read this. For the most recent updates on COVID-19, visit our coronavirus news page. 

5 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Hoffman HH, Schneider WM, Rozen-Gagnon K, et al. TMEM41B is a pan-flavivirus host factor. Cell. December 2020. doi:10.1016/j.cell.2020.12.005

  2. Schneider WM, Luna JM, Hoffmann HH, et al. Genome-scale identification of SARS-CoV-2 and pan-coronavirus host factor networks. Cell. 2021. doi:10.1016/j.cell.2020.12.006

  3. National Institutes of Health. SARS-CoV-2 may use key carbohydrate to infect cells. October 6, 2020.

  4. Huang Y, Yang C, Xu Xf. et al. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19Acta Pharmacol Sin. 2020;41:1141–1149. doi:10.1038/s41401-020-0485-4

  5. Moretti F, Bergman P, Dodgson S, et al. TMEM41b is a novel regulator of autophagy and lipid mobilization. EMBO Rep. 2018;19(9):e45889. doi:10.15252/embr.201845889

By Jocelyn Solis-Moreira
Jocelyn Solis-Moreira is a journalist specializing in health and science news. She holds a Masters in Psychology concentrating on Behavioral Neuroscience.