Abstract
COVID-19 is an infectious respiratory illness caused by the virus strain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and until now, there is no effective therapy against COVID-19. Since SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) for entering into host cells, to target COVID-19 from therapeutic angle, we engineered a hexapeptide corresponding to the ACE2-interacting domain of SARS-CoV-2 (AIDS) that inhibits the association between receptor-binding domain-containing spike S1 and ACE-2. Accordingly, wild type (wt), but not mutated (m), AIDS peptide inhibited SARS-CoV-2 spike S1-induced activation of NF-κB and expression of IL-6 in human lungs cells. Interestingly, intranasal intoxication of C57/BL6 mice with recombinant SARS-CoV-2 spike S1 led to fever, increase in IL-6 in lungs, infiltration of neutrophils into the lungs, arrhythmias, and impairment in locomotor activities, mimicking some of the important symptoms of COVID-19. However, intranasal treatment with wtAIDS, but not mAIDS, peptide reduced fever, protected lungs, improved heart function, and enhanced locomotor activities in SARS-CoV-2 spike S1-intoxicated mice. Therefore, selective targeting of ACE2-to-SARS-CoV-2 interaction by wtAIDS may be beneficial for COVID-19.
Keywords: ACE-2; Arrhythmias; COVID-19; Fever; Lung inflammation; Spike S1.
【저자키워드】 COVID-19, ACE-2, Fever, Arrhythmias, Lung inflammation, Spike S1., 【초록키워드】 Treatment, SARS-CoV-2, ACE2, coronavirus, spike, IL-6, peptide, angiotensin-converting enzyme 2, activity, cells, mice, AIDS, Lungs, human lung, therapeutic, expression, wild type, intranasal, SARS-CoV-2 spike, NF-κB, association, Interaction, host cells, acute respiratory syndrome, Activation, domain, activities, effective therapy, symptoms of COVID-19, impairment, selective, virus strain, bind, infectious respiratory illness, caused, inhibit, inhibited, reduced, increase in, mutated, mimicking, infiltration of neutrophil, locomotor, 【제목키워드】 SARS-CoV-2, AIDS, heart, COVID-19 therapy,