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: SARS-CoV-2; angiotensin-converting enzyme-2; cathelicidin; receptor binding domain; spike.
【저자키워드】 SARS-CoV-2, spike, Receptor binding domain, Cathelicidin, angiotensin-converting enzyme-2, 【초록키워드】 COVID-19, Treatment, coronavirus disease, Coronavirus disease 2019, ACE2, SARS-COV-2 infection, Human, Infection, peptide, Lung infection, in vitro, Receptor binding domain, Adenovirus, human ACE2, Protein, Receptor-binding domain, mice, RBD, Cathelicidin, mechanisms, recruitment, angiotensin-converting enzyme-2, inhibitor, affinity, association, Angiotensin-converting enzyme, Interaction, administration, angiotensin, Receptor binding, Invasion, half-maximal inhibitory concentration, enzyme, domain, high affinity, blockade, SARS-CoV-2 S, targeting, antimicrobial peptide, Host, Cell, decrease, bind, subsequent, inhibit, the RBD, the receptor-binding domain, expressing, 【제목키워드】 Human, Cathelicidin, Stone, Bird,