Discovery of Small Anti-ACE2 Peptides to Inhibit SARS-CoV-2 Infectivity.
Pratik Adhikary,Sashi Kandel,Umar-Farouk Mamani,Bahaa Mustafa,Siyuan Hao,Jianming Qiu,John Peter Fetse,Yanli Liu,Nurudeen Mohammed Ibrahim,Yongren Li,Chien Yu Lin,Evanthia Omoscharka,Kun Cheng +12 more
- Vol. 4, Iss: 7, pp 2100087-2100087
TLDR
Using a novel biopanning strategy, a small anti‐ACE2 peptide is discovered, which shows high affinity and specificity to human ACE2 and inhibits SARS‐CoV‐2 infection in Vero‐E6 cells and Huh7 cells.Abstract:
COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which infects host cells by binding its viral spike protein receptor-binding domain (RBD) to the angiotensin converting enzyme 2 (ACE2) on host cells. Blocking the SARS-CoV-2-RBD/ACE2 interaction is, therefore, a potential strategy to inhibit viral infections. Using a novel biopanning strategy, a small anti-ACE2 peptide is discovered, which shows high affinity and specificity to human ACE2. It blocks not only the SARS-CoV-2-RBD/ACE2 interaction but also the SARS-CoV-1-RBD/ACE2 interaction. Moreover, it inhibits SARS-CoV-2 infection in Vero-E6 cells. The peptide shows negligible cytotoxicity in Vero-E6 cells and Huh7 cells. In vivo short-term lung toxicity study also demonstrates a good safety of the peptide after intratracheal administration. The anti-ACE2 peptide can be potentially used as a prophylactic or therapeutic agent for SARS-CoV-2 or other ACE2-mediated viruses. The strategy used in this study also provides a fast-track platform to discover other antiviral peptides, which will prepare the world for future pandemics.read more
Citations
More filters
Journal ArticleDOI
Computational Design of Miniproteins as SARS-CoV-2 Therapeutic Inhibitors
TL;DR: In this study, the structure of lead antiviral candidate binder (LCB1), which has three alpha-helices (H1, H2, and H3), is used as a template to design and simulate several miniprotein RBD inhibitors and atomic-scale details on the role of hydrogen bonding and partial charge distribution in stabilizing the minibinder:RBD complex are provided.
Journal ArticleDOI
Discovery of Cyclic Peptide Inhibitors Targeting PD-L1 for Cancer Immunotherapy.
John Peter Fetse,Zhen Zhao,Hao Liu,Umar-Farouk Mamani,Bahaa Mustafa,Pratik Adhikary,Mohammed Ibrahim,Yanli Liu,P. Patel,Maryam Nakhjiri,Mohammed Mushabab Alahmari,Guang-Zhang Li,Kun Cheng +12 more
TL;DR: The results demonstrate that macrocyclization scanning is an effective way to improve the serum stability and bioactivity of the anti-PD-L1 linear peptide and can be employed in the optimization of other bioactive peptides, particularly those for protein-protein interaction modulation.
Journal ArticleDOI
SARS-CoV-2 pan-variant inhibitory peptides deter S1-ACE2 interaction and neutralize delta and omicron pseudoviruses
TL;DR: Wang et al. as discussed by the authors deployed interactive structure and pharmacophore-based approaches to design short and stable peptides -Coronavirus Spike Neutralizing Peptides (CSNPs)- capable of neutralizing all SARS-CoV-2 VOCs.
Journal ArticleDOI
Peptides and peptidomimetics as therapeutic agents for Covid-19
TL;DR: This review is focused on peptides and peptidomimetics as PPI modulators and protease inhibitors against SARS‐CoV‐2.
Journal ArticleDOI
Ultrasmall Coordination Polymers for Alleviating ROS-Mediated Inflammatory and Realizing Neuroprotection against Parkinson's Disease
Guowang Cheng,Xueliang Liu,Yujing Liu,Yao Liu,Rui Ma,Jingshan Luo,Xinyi Zhou,Zhen Wu,Zhuanghua Liu,Tongkai Chen +9 more
TL;DR: This study puts forth a unique type of therapeutics-based NCPs that could be used for safe and efficient treatment of PD with potential in clinical translation, and shows efficient neuroprotection by scavenging excessive radicals and suppressing neuroinflammation.
References
More filters
Journal ArticleDOI
A pneumonia outbreak associated with a new coronavirus of probable bat origin
Peng Zhou,Xing-Lou Yang,Xian Guang Wang,Ben Hu,Lei Zhang,Wei Zhang,Hao Rui Si,Yan Zhu,Bei Li,Chao Lin Huang,Hui-Dong Chen,Jing Chen,Yun Luo,Hua Guo,Ren Di Jiang,Meiqin Liu,Ying Chen,Xu Rui Shen,Xi Wang,Xiao Shuang Zheng,Kai Zhao,Quanjiao Chen,Fei Deng,Lin Lin Liu,Bing Yan,Fa Xian Zhan,Yan-Yi Wang,Gengfu Xiao,Zhengli Shi +28 more
TL;DR: Identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China, and it is shown that this virus belongs to the species of SARSr-CoV, indicates that the virus is related to a bat coronav virus.
Journal ArticleDOI
Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein.
Alexandra C. Walls,Young-Jun Park,M. Alejandra Tortorici,M. Alejandra Tortorici,Abigail Wall,Andrew T. McGuire,Andrew T. McGuire,David Veesler +7 more
TL;DR: It is demonstrating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination, and it is shown that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of Sars- coV- 2 S and SARS S bind with similar affinities to human ACE2, correlating with the efficient spread of SATS among humans.
Journal ArticleDOI
Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis
TL;DR: ACE2 is abundantly present in humans in the epithelia of the lung and small intestine, which might provide possible routes of entry for the SARS‐CoV.
Journal ArticleDOI
Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor.
Jun Lan,Jiwan Ge,Jinfang Yu,Sisi Shan,Huan Zhou,Shilong Fan,Qi Zhang,Xuanling Shi,Qisheng Wang,Linqi Zhang,Xinquan Wang +10 more
TL;DR: High-resolution crystal structures of the receptor-binding domain of the spike protein of SARS-CoV-2 and SARS -CoV in complex with ACE2 provide insights into the binding mode of these coronaviruses and highlight essential ACE2-interacting residues.
Journal ArticleDOI
A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19.
Bin Cao,Yeming Wang,Danning Wen,Wen Liu,Jingli Wang,Guohui Fan,Lianguo Ruan,Bin Song,Yanping Cai,Ming Wei,Xingwang Li,Jia'an Xia,Nanshan Chen,Jie Xiang,Ting Yu,Tao Bai,Xuelei Xie,Li Zhang,Caihong Li,Ye Yuan,Hua Chen,Huadong Li,Hanping Huang,Shengjing Tu,Fengyun Gong,Ying Liu,Yuan Wei,Chongya Dong,Fei Zhou,Xiaoying Gu,Jiuyang Xu,Zhibo Liu,Yi Zhang,Li Hui,Lianhan Shang,Ke Wang,Kunxia Li,Xia Zhou,Xuan Dong,Zhaohui Qu,Sixia Lu,Xujuan Hu,Shunan Ruan,Shanshan Luo,Jing Wu,Lu Peng,Fang Cheng,Lihong Pan,Jun Zou,Chunmin Jia,Juan Wang,Xia Liu,Shuzhen Wang,Xudong Wu,Qin Ge,Jing He,Haiyan Zhan,Fang Qiu,Li Guo,Chaolin Huang,Thomas Jaki,Frederick G. Hayden,Peter Horby,Dingyu Zhang,Chen Wang +64 more
TL;DR: In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir–ritonavir treatment beyond standard care, and future trials in patients withsevere illness may help to confirm or exclude the possibility of a treatment benefit.
Related Papers (5)
Circulating ACE2-expressing Exosomes Block SARS-CoV-2 Virus Infection as an Innate Antiviral Mechanism
Lamiaa El-Shennawy,Andrew D. Hoffmann,Nurmaa Dashzeveg,Paul J. Mehl,Zihao Yu,Valerie Tokars,Vlad Nicolaescu,Carolina Ostiguin,Yuzhi Jia,Lin Li,Kevin Furlong,Chengsheng Mao,Jan Wysocki,Daniel Batlle,Thomas J. Hope,Yang Shen,Yuan Luo,Young Kwang Chae,Hui Zhang,Suchitra Swaminathan,Glenn Randall,Alexis R. Demonbreun,Michael G. Ison,Deyu Fang,Huiping Liu +24 more