Mutating novel interaction sites in NRP1 reduces SARS-CoV-2 spike protein internalization.

ABSTRACT: The global pandemic of coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has become a severe global health problem because of its rapid spread. Both Ace2 and NRP1 provide initial viral binding sites for SARS-CoV-2. Here, we show that cysteine residues located in the vestigial plasminogen-apple-nematode (PAN) domain of NRP1 are necessary for SARS-CoV-2 spike protein internalization. Mutating novel cysteine residues in the PAN altered NRP1 stability and downstream activation of extracellular signal-regulated kinase (ERK) signaling pathway and impaired its interaction with the spike protein. This resulted in a significant reduction in spike protein abundance in Vero-E6 cells for the original, alpha, and delta SARS-CoV-2 variants even in the

SUBMITTER: Pal D 

PROVIDER: S-EPMC9957656 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature