期刊
FRONTIERS IN PHARMACOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2021.685161
关键词
coronavirus; MERS-CoV; fusion inhibitors; antivirals; drug discovery
资金
- Deanship of Scientific Research at King Faisal University [171001]
- National Research Foundation - Ministry of Science and ICT in the Republic of Korea [2016M3A9B6916708]
- Ministry of Education, Culture, Sports, Science, and Technology, Japan [16H06575]
- Japan Society for the Promotion of Science [18K15235, 20K07610]
- Japan Agency for Medical Research and Development (AMED) (Program of Japan Initiative for Global Research Network on Infectious Diseases (JGRID)) [JP20wm0125002]
- Grants-in-Aid for Scientific Research [16H06575, 20K07610, 18K15235] Funding Source: KAKEN
- National Research Foundation of Korea [2016M3A9B6916708] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
A highly potent set of peptides was designed to prevent MERS-CoV fusion through competition with HR2 at its HR1 binding site. These peptides demonstrated strong inhibition of MERS-CoV cell-cell fusion and plaque formation, with no cytotoxic effects at high concentrations, suggesting their potential as promising antiviral agents.
Middle East respiratory syndrome coronavirus (MERS-CoV), capable of zoonotic transmission, has been associated with emerging viral pneumonia in humans. In this study, a set of highly potent peptides were designed to prevent MERS-CoV fusion through competition with heptad repeat domain 2 (HR2) at its HR1 binding site. We designed eleven peptides with stronger estimated HR1 binding affinities than the wild-type peptide to prevent viral fusion with the cell membrane. Eight peptides showed strong inhibition of spike-mediated MERS-CoV cell-cell fusion with IC50 values in the nanomolar range (0.25-2.3 mu M). Peptides #4-6 inhibited 95-98.3% of MERS-CoV plaque formation. Notably, peptide four showed strong inhibition of MERS-CoV plaques formation with EC50 = 0.302 mu M. All peptides demonstrated safe profiles without cytotoxicity up to a concentration of 10 mu M, and this cellular safety, combined with their anti-MERS-CoV antiviral activity, indicate all peptides can be regarded as potential promising antiviral agents.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据