Coronavirus disease 2019 (COVID-19) continuously proceeds despite the application of a variety of vaccines. It is still urgent to find effective ways to treat COVID-19. Recent studies indicate that NRP1, an important receptor of the natural peptide tuftsin, facilitates SARS-CoV-2 infection. Importantly, tuftsin is a natural human molecule released from IgG. Here, we found 91 overlapping genes between tuftsin targets and COVID-19-associated genes. Bioinformatics analyses indicated that tuftsin could also target ACE2 and exert some immune-related functions to treat COVID-19. Using surface plasmon resonance (SPR) analysis, we confirmed that tuftsin can bind ACE2 and NRP1 directly. Moreover, tuftsin effectively impairs the binding of SARS-CoV-2 S1 to ACE2. Thus, tuftsin is an attractive drug against COVID-19. And tuftsin as natural immunostimulating peptide in human, we speculate that tuftsin may has crucial roles in asymptomatic carriers or mild cases of COVID-19.
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