CBNU News

Image title: Human cyclophilin A: Potential therapeutic agent against COVID-19

Image caption: Researchers have found that the protein human cyclophilin A binds strongly with receptor-binding site of SARS-CoV-2, suggesting that it could prevent coronavirus infection

Image credit: Ji-Yung Ahn and Yang-Hoon Kim from Chungbuk National University

License type: Original Content

Usage restrictions: Cannot be reused without permission

Chungbuk National University Researchers Demonstrate the Utility of Human Cyclophilin A Against SARS-CoV-2

Researchers reveal that the protein human cyclophilin A binds strongly to the spike protein of SARS-CoV-2 which may help prevent viral entry into human cells

Antiviral drugs currently used to treat COVID-19 may cause adverse effects, necessitating new therapies against SARS-CoV-2. Researchers have now found that a human protein known as cyclophilin A binds strongly with the receptor-binding region of the spike protein of SARS-CoV-2. Once bound, cyclophilin A prevents the viral spike protein from binding with the cell surface receptor in human cells. Findings suggest that human cyclophilin A can serve as a novel therapy for diseases caused by coronaviruses that work by preventing viral entry into human cells.

The recent COVID-19 pandemic brought to the forefront the ability of coronaviruses to mutate rapidly. Seven types of coronaviruses are currently known to cause respiratory infections in humans, each with mutated variants linked to different attributes like transmissibility. Therefore, specific treatments are needed to manage infections during subsequent infection cycles.

Currently, treatment approaches for serious SARS-CoV-2 infection involve the administration of nirmatrelvir or ritonavir. The safety profile of these antiviral drugs has not been determined conclusively. Therefore, there may be unforeseen, sometimes fatal, side effects linked to their use. Moreover, the emergence of multiple SARS-CoV-2 variants necessitates the development of new treatment modalities.

To this end, in a study published online in Bioengineering and Translational Medicine on October 27, 2022, a team of researchers led by Ji-Yung Ahn and Yang-Hoon Kim of Chungbuk National University suggested a novel treatment approach to SARS-CoV-2 in the form of extracellular human cyclophilin A (hCypA)—a protein with key roles in the immune system. The team found that hCypA binds to the spike protein of SARS-CoV-2 at its receptor-binding domain. As a result, it blocks the virus from binding to the ACE2 receptor of human cells, which is its only pathway to infect cells.

It was further revealed that hCypA binds strongly with the SARS-CoV-2 receptor-binding domain and that the hCypA-SARS-CoV-2 protein complex successfully prevents ACE2 from binding to the receptor-binding domain. "The molecular interaction between hCypA and the viral protein interface was depicted using three-dimensional structural analyses, which revealed the blocking of key residues on the RBD interface by hCypA" Professor Ahn explains.

The study's findings suggest that hCypA may be a potent and specific therapeutic agent against SARS-CoV-2. "The hCypA–RBD interaction highlights a new strategy for preventing a possible SARS-CoV-2 infection pathway against host cells and serves as a feasible approach for preventing SARS-CoV-2 infection," adds Professor Ahn.

Human cyclophilin A has a strong affinity for SARS-CoV-2 for a reason. After a human cell gets infected with a coronavirus, the hCypA inside it plays a crucial role in facilitating the viral replication. Therefore, coronaviruses have to interact strongly with hCypA. As Professor Kim notes, "The protein hCypA plays a critical role in the life cycle of many viruses such as HCoV-229 E, HCoV-NL63, FPIV, SARS-CoV, and MERS-CoV." Therefore, the current study impressively turns a protein interaction normally beneficial for the virus into a potent tool that stops its infection.

The researchers also found that hCypA’s strong affinity to the receptor-binding site is maintained across several SARS-CoV-2 variants. Hopefully, this implies that newly emerging coronavirus variants will not be able to develop resistance against hCypA therapy. "The emergence of variants with mutations in the SARS-CoV-2 spike protein affects the binding ability of the virus to the ACE2 receptor. New variants may also exhibit high transmissibility and faster spreading. However, our research showed that many coronaviruses and their variants can be inhibited by hCypA," concludes Professor Kim.

We are hopeful about the research team’s strategy and cannot wait for it to bear fruits.

Reference

About Chungbuk National University:

Chungbuk National University, located in Cheongju, South Korea, is a distinguished institution renowned for its commitment to academic excellence, research innovation, and community engagement. Founded in 1951, the university offers a wide spectrum of undergraduate, graduate, and doctoral programs spanning diverse fields and maintaining rigorous academic standards. It is a hub of cutting-edge research, with numerous research centers and institutes dedicated to technological advancements, healthcare, agriculture, and cultural studies.

About Prof. Ji-Yung Ahn from Chungbuk National University:

Ji-Young Ahn is currently a professor at the Department of Microbiology at Chungbuk National University. Prof. Ahn received her bachelor’s as well as master’s degree in microbiology, from Busan National University in 2000 and 2002, respectively. In 2006, she obtained her Ph.D. in Chemical Engineering, at the University of Korea. Since 2021, she became a professor at the Department of Microbiology at Chungbuk National University. Prof Ahn has more than 20 years of experience in the field of microbiology. She has published, co-authored, and was a corresponding author for several articles in the field of capturing agents (peptide, aptamer, antibody) against small molecules such as toxins, and chemicals, in addition to proteins. Her research also focuses on the risk assessment of engineered nanocomplexes -aptamer and nanoparticles.

About Prof. Yang-Hoon Kim from Chungbuk National University:

Yang-Hoon Kim is a professor at the Department of Microbiology and director of the Center of Ecology and Environmental Toxicology (CEET) at Chungbuk National University. He was awarded his bachelor’s degree from the Department of Chemical Engineering, Chosun University, Gwangju in 1997. Subsequently, from the same university at the Department of Environmental Science and Engineering, he received his master’s and Ph.D. degrees in 1999 and 2003, respectively. Prof Kim has more than 20 years of experience, and has published, co-authored, and been a corresponding author for several articles, in addition to writing four book chapters. His current research focuses on high-throughput selection, characterization, and application of DNA and RNA aptamers, screening for novel disease biomarkers and mechanism of molecular targets, in addition to structural and functional analysis of biomolecules-aptamer and protein-aptamer complexes.