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Monoclonal Antibody CT-P59: Another Silver Bullet Against Novel Coronavirus
  • 작성일2021-11-08
  • 최종수정일2021-11-08
  • 담당부서연구기획과
  • 연락처043-719-8033

Monoclonal Antibody CT-P59: Another Silver Bullet Against Novel Coronavirus

Researchers in Korea report a novel monoclonal antibody called CT-P59 against SARS-CoV-2, offering hope for effective therapy and prophylaxis

As the COVID-19 pandemic rages on across the world, researchers have been hard at work to identify therapeutics that can effectively check SARS-CoV-2, the disease-causing pathogen. One such attempt by a group of researchers in Korea has yielded the monoclonal antibody CT-P59, which effectively neutralizes SARS-CoV-2, according to a study published in Nature Communications, offering a potential new therapy against COVID-19. 


Korean researchers have identified an effective monoclonal antibody, CT-P59, against the novel coronavirus

Korean researchers have identified an effective monoclonal antibody, CT-P59, against the novel coronavirus

Image courtesy: Shutterstock



The ongoing COVID-19 pandemic has posed a serious challenge for the medical community and the healthcare sector in most countries. Despite research going on at war footing on vaccines and therapeutics across the globe, the available treatment options are limited, both in diversity and effectiveness. In this regard, convalescent plasma therapy with antibodies that neutralize the virus and obtained from patients recovering from COVID-19 is under investigation.


The therapy involves treating patients with a concoction of antibodies that bind to the virus, inhibiting it, thereby alleviating the severe symptoms of the disease. However, this strategy is plagued by shortcomings like scalability issues and lot-to-lot variations. To avoid these disadvantages, researchers have been investigating specific antibodies that will have the most effect against the virus.


According to a recent study published in Nature Communications, a group of researchers in Korea have now succeeded in identifying an effective neutralizing antibody against SARS-CoV-2, called the CT-P59. This inventive work was accomplished under the collaboration of the governmental institute,  National Institute of Health, and private agencies, and was supported by a Korea National Institute of Health fund (2020-ER5311-00,2020-ER5323-00, 2019-NI-077-01, 2019-NG-044-01).


In the current study, the researchers identified CT-P59 from an antibody library (collection of antibodies that develop in the body in response to an antigenic stimulus), constructed from peripheral blood mononuclear cells of a patient recovering from COVID-19. After identifying CT-P59, they enumerated these as monoclonal antibodies (mAb) in the laboratory, with selective specificity for the viral antigen, eventually redesigning them into fully human antibodies. The therapeutic efficacy of these mAbs was evaluated in animal models of COVID-19, including hamsters, ferrets, and rhesus monkeys. The results were promising, which encouraged the researchers to progress to the next step.


The researchers found that CT-P59 potentially neutralizes SARS-CoV-2 isolates without causing antibody-dependent enhancement, in which there is an immune system-mediated aggravation of the disease in patients. To determine the precise mechanism by which CT-P59 achieves this, they analyzed the interaction of the antibody with the virus using X-ray crystallography that ‘stops’ the biomolecular event at the point of inquiry.


The researchers observed that CT-P59 bound to the receptor binding domain (RBD) of the viral surface spike protein blocks substantial areas of the target host cellular receptor, angiotensin converting enzyme 2 (ACE2), which prevents the virus from interacting with the target host cell. As a spokesperson for the team explains,, “Complex crystal structure of the virus-host biomolecular interaction shows that CT-P59 blocks interaction regions of RBD for ACE2 receptor with an orientation that is notably different from previously reported RBD-targeting mAb.” Moreover, CT-P59 does not bind to the frequently mutated amino acid residues at position 367, 436, or 364 of the RBD; this suggests the antibody can effectively neutralize naturally occurring mutated forms of the virus. In addition, the researchers found that CT-P59 treatment in COVID-19 animal models not only substantially reduced viral titers, but also alleviated the clinical symptoms. A trove of good news in the middle of the ongoing COVID-19 ‘battle’, indeed!


The research team is confident about the potential of this innovative study: “CT-P59 is a promising treatment for COVID-19 patients as well as a prophylactic option. The effectiveness and safety of CT-P59 have been proven in phase I and II clinical trials; phase III clinical trials are currently underway in South Korea and other countries.


For a COVID-19-battered world, nothing could be a more welcome news!



Reference

Authors

Title of original paper

Journal

Cheolmin Kim, Dong-Kyun Ryu, Jihun Lee, Young-Il Kim, Ji-Min Seo, Yeon-Gil Kim, Jae-Hee Jeong, Minsoo Kim, Jong-In Kim, Pankyeom Kim, Jin Soo Bae, Eun Yeong Shim, Min Seob Lee, Man Su Kim, Hanmi Noh, Geun-Soo Park, Jae Sang Park, Dain Son, Yongjin An, Jeong No Lee, Ki-Sung Kwon, Joo-Yeon Lee, Hansaem Lee, Jeong-Sun Yang, Kyung-Chang Kim, Sung Soon Kim, Hye-Min Woo, Jun-Won Kim, Man-Seong Park, Kwang-Min Yu, Se-Mi Kim, Eun-Ha Kim, Su-Jin Park, Seong Tae Jeong, Chi Ho Yu, Youngjo Song, Se Hun Gu, Hanseul Oh, Bon-Sang Koo,

Jung Joo Hong, Choong-Min Ryu, Wan Beom Park, Myoung-don Oh, Young Ki Choi, and Soo-Young Lee

A therapeutic neutralizing antibody targeting receptor binding domain of SARS-CoV-2 spike protein

Nature Communications

DOI

Affiliations

https://doi.org/10.1038/s41467-020-20602-5

Biotechnology Research Institute, Celltrion Inc., Incheon; College of Medicine and Medical Research Institute, Chungbuk National

University, Cheongju; Pohang Accelerator Laboratory, Pohang University of Science and Technology, Pohang, Kyungbuk; Center for Infectious Diseases Research, Korea National Institute of Health, Korea Centers for Disease Control and Prevention Agency, Cheongju; Department of Microbiology and Institute for Viral Diseases, College of Medicine, Korea University, Seoul; The 4th R&D Institute, Agency for Defense Development, Yuseong, Daejeon; National Primate Research Centre, Korea Research Institute of Bioscience and Biotechnology, Cheongju; Infectious Disease Research Centre, Korea Research Institute of Bioscience and Biotechnology, Daejeon; Department of Internal Medicine, Seoul National University College of Medicine, Seoul; and Division of Applied Life Science and Research Institute of Life Sciences, Gyeongsang National University, Jinju


About National Institute of Health in Korea 

The Korea National Institute of Health (KNIH), one of the major operating components of the Ministry of Health and Welfare affiliated to the Korea Disease control and Prevention, leads the nation’s medical research. Over the past seven decades, the KNIH has made unwavering efforts to enhance the public’s health and innovate biomedical research. The KNIH seeks to eradicate diseases and make people healthier. The KNIH establishes a scientific basis and evidence underlying health policy as well as provides national research infrastructures. We also promote public health research. To this end, we make efforts to enrich a health research environment by granting funds to research projects and keeping our resources, data, and facilities more open and accessible to researchers.


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