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Mol. Ther., Mar 25 2024, S1525-0016(24)00170-9 | https://doi.org/10.1016/j.ymthe.2024.03.029 In vitro and in vivo validation of the antiviral effect of hCypA against SARS-CoV-2 via binding to the RBD of spike protein

Woo-Ri Shin^1,2,†, Do-Young Kim^1,†, Sang Yong Kim^3,†, Gna Ahn^1,4, Dae-Young Park^1,4 , Jiho Min^5*, Ji-Young Ahn^1*, and Yang-Hoon Kim^1*

¹Department of Microbiology, Chungbuk National University, 1 Chungdae-Ro, Seowon-Gu, Cheongju 28644, South Korea

²Department of Bioengineering, University of Pennsylvania, 210 S 33rd St., Philadelphia, PA 19104, USA

³Department of Food Science and Biotechnology, Shin Ansan University, Danwon-Gu, Ansan, 15435, Republic of Korea

⁴Center for Ecology and Environmental Toxicology, Chungbuk National University, Cheongju 28644, Republic of Korea

⁵Graduate School of Semiconductor and Chemical Engineering, Jeonbuk National University, 567 Baekje-daero, Deokjin-Gu Jeonju, Jeonbuk 54896, South Korea

^†These authors contributed equally to this work.

^*Correspondence should be addressed to YHK, JYA, and JM

Abstract

The novel coronavirus disease 2019 has stimulated the rapid development of new biological therapeutics to inhibit SARS-CoV-2 infection; however, this remains a challenging task. In a previous study using structural analysis, we revealed that human cyclophilin A inhibits the entry of SARS-CoV-2 into host cells by interfering with the interaction of the receptor-binding domain of the spike protein with angiotensin-converting enzyme 2 on the host cell surface, highlighting its potential for antiviral therapy. For a comprehensive experimental validation, in this study, we verified the antiviral effects of human cyclophilin A against SARS-CoV-2, including its variants, using in vitro assays and experiments on an in vivo mouse model. Human cyclophilin A demonstrated a highly effective antiviral effect, with an 85% survival rate upon SARS-CoV-2 infection. It also reduced viral titers, inflammation in the lungs and brain, and cytokine release in the serum, suggesting a controlled immune response and potentially faster recovery. Overall, our study provides insights into the potential of human cyclophilin A as a therapeutic agent against SARS-CoV-2, which should guide future clinical trials that might provide an additional therapeutic option for patients.

논문정보

형식Research article
게재일2024년 03월 (BRIC 등록일 2024-04-01)
연구진국내(교신)+국외 연구진
분야 생명과학 > 생물공학

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