ACE-2-interacting Domain of SARS-CoV-2 (AIDS) Peptide Suppresses Inflammation to Reduce Fever and Protect Lungs and Heart in Mice: Implications for COVID-19 Therapy

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.

Conserved in 186 Countries The RBD Fraction of SARS CoV-2 S-Protein With in-Silico T500S Mutation Strongly Blocks ACE2 Rejecting The Viral Spike; A Molecular-Docking Analysis.

“…Several organ-protecting effects of this hexapeptide justify more intense work in this aspect [19]. However, in the current study we demonstrated that in-silico specific amino acid alteration in the highly conserved S protein of the SARS CoV 2 can potentially block its ACE2 Where, SM3 and DM2 showed more affinity to ACE2.…”

“…Similar type of study suggests that engineered ACE2 receptor traps can neutralize SARS-CoV-2 [18]. A hexapeptide in core of spike RBD inhibits the association between spike S1 and ACE-2 [19].…”

Computational screening of 645 antiviral peptides against the receptor-binding domain of the spike protein in SARS-CoV-2

“…In a previous study, the effectiveness of peptides against the S1 protein of SARS-CoV-1 was established [ 28 ]. In another study, a corresponding hexapeptide to the ACE-interacting domain of SARS-CoV-2 (AIDS) has been found to disrupt the association between RBD-ACE2 in mice[ 29 ]. Karoyan and colleagues designed peptide-mimics which has been found to inhibit S protein with inhibitory concentration (IC50) in nanomolar range [ 30 ].…”

Conserved in 186 countries the RBD fraction of SARS CoV-2 S-protein with in-silicoT500S mutation strongly blocks ACE2 rejecting the viral spike; A Molecular-docking analysis

“…But as this peptide is a very short fragment having no higher-order of protein structure so the effect may not be due to the complementarily based S1 and ACE-2 binding. Several organ-protecting effects of this hexapeptide justify more intense work in this aspect [19]. However, in the current study we demonstrated that in-silico specific amino acid alteration in the highly conserved S protein of the SARS CoV 2 can potentially block its ACE2 binding, hence minimize the viral infection.…”

“…Several organ-protecting effects of this hexapeptide justify more intense work in this aspect [19]. However, in the current study we demonstrated that in-silico specific amino acid alteration in the highly conserved S protein of the SARS CoV 2 can potentially block its ACE2 Whereas for complete spike glycoprotein (6vyb1), Mutated CUT4 get more preference in ACE2 attachment as they showed binding affinity of -11.8, -11.9 and -11.9 respectively.…”