期刊
ACS INFECTIOUS DISEASES
卷 7, 期 6, 页码 1545-1554出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsinfecdis.1c00096
关键词
cathelicidin; SARS-CoV-2; spike; receptor binding domain; angiotensin-converting enzyme-2
资金
- Natural Science Fund of Chongqing City [cstc2019jcyj-msxmX0011]
- National Natural Science Foundation of China [81725019, 32070662, 61832019]
- Program for Scientific and Technological Innovation Leader of Chongqing [CQYC201903084]
- Key Research Area Grant of the Ministry of Science and Technology of China [2016YFA0501703]
The study showed that human cathelicidin LL37 can block the viral S1 and cloak ACE2 simultaneously, providing a potential candidate for COVID-19 prevention and treatment.
SARS-CoV-2 infection begins with the association of its spike 1 (S1) protein with host angiotensin-converting enzyme-2 (ACE2). Targeting the interaction between S1 and ACE2 is a practical strategy against SARS-CoV-2 infection. Herein, we show encouraging results indicating that human cathelicidin LL37 can simultaneously block viral S1 and cloak ACE2. LL37 binds to the receptor-binding domain (RBD) of S1 with high affinity (11.2 nM) and decreases subsequent recruitment of ACE2. Owing to the RBD blockade, LL37 inhibits SARS-CoV-2 S pseudovirion infection, with a half-maximal inhibitory concentration of 4.74 mu g/mL. Interestingly, LL37 also binds to ACE2 with an affinity of 25.5 nM and cloaks the ligand-binding domain (LBD), thereby decreasing Si adherence and protecting cells against pseudovirion infection in vitro. Intranasal administration of LL37 to C57 mice infected with adenovirus expressing human ACE2 either before or after pseudovirion invasion decreased lung infection. The study identified a versatile antimicrobial peptide in humans as an inhibitor of SARS-CoV-2 attachment using dual mechanisms, thus providing a potential candidate for coronavirus disease 2019 (COVID-19) prevention and treatment.
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