Coronavirus disease 2019 (COVID-19) continuously progresses despite the application of a variety of
vaccines. Therefore, it is still imperative to find effective ways for treating
COVID-19. Recent studies indicate that NRP1, an important receptor of the natural
peptide tuftsin (released from
IgG), facilitates
SARS-CoV-2 infection. Here, we found 91 overlapping genes between
tuftsin targets and COVID-19-associated genes. We have demonstrated that
tuftsin could also target ACE2 and exert some immune-related functions. Molecular docking results revealed that tustin could combine with ACE2 and NRP1 in stable structures, and their interacted regions cover the binding surfaces of S1-protein with the two receptors. Using surface plasmon resonance (SPR) analysis, we confirmed that
tuftsin can bind ACE2 and NRP1 directly. Importantly, using SPR-based competition assay we have shown here that
tuftsin effectively prevented the binding of SARS-CoV-2 S1-protein to ACE2. Collectively, these data suggest that
tuftsin is an attractive therapeutic candidate against
COVID-19 and can be considered for translational as well as clinical studies.