Human Cathelicidin Inhibits SARS-CoV-2 Infection: Killing Two Birds with One Stone.
ACS Infect Dis
; 7(6): 1545-1554, 2021 06 11.
Article
in English
| MEDLINE | ID: covidwho-1182792
ABSTRACT
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 µg/mL. Interestingly, LL37 also binds to ACE2 with an affinity of 25.5 nM and cloaks the ligand-binding domain (LBD), thereby decreasing S1 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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antimicrobial Cationic Peptides
/
Virus Attachment
/
Spike Glycoprotein, Coronavirus
/
COVID-19
Type of study:
Experimental Studies
Limits:
Animals
/
Humans
Language:
English
Journal:
ACS Infect Dis
Year:
2021
Document Type:
Article
Affiliation country:
Acsinfecdis.1c00096
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