PMC:7100515 / 15293-17310 JSONTXT 12 Projects

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Id Subject Object Predicate Lexical cue
T114 0-46 Sentence denotes PIKfyve and TPC2 critical for SARS-CoV-2 entry
T115 47-106 Sentence denotes Phosphoinositides play many essential roles in endocytosis.
T116 107-239 Sentence denotes Among them, one is phosphatidylinositol-3,5-bisphosphate (PI(3,5)P2), which regulates early endosome to late endosome dynamics33,34.
T117 240-352 Sentence denotes Phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) is the main enzyme synthesizing PI(3,5)P2 in early endosome.
T118 353-434 Sentence denotes HEK 293/hACE2 cells were treated with apilimod, a potent inhibitor for PIKfyve35.
T119 435-672 Sentence denotes Inhibition of PIKfyve by apilimod significantly reduced entry of SARS-CoV S pseudovirions on 293/hACE2 cells in a dose dependent manner (Fig. 3b), whereas it had no effect on entry of VSV-G pseudovirions, which occurs in early endosomes.
T120 673-967 Sentence denotes Similar inhibitory effects were observed when HeLa/hDPP4 cells and HeLa cells stably expressing mouse carcinoembryonic antigen related cell adhesion molecule 1a (mCEACAM1a) (HeLa/mCEACAM1a) were treated with apilimod and transduced with MERS-CoV and MHV S pseudovirions (Fig. 3b), respectively.
T121 968-1076 Sentence denotes Moreover, infection of live MHV on 17Cl.1 cells was also strongly inhibited by apilimod treatment (Fig. 3c).
T122 1077-1169 Sentence denotes No significant cell toxicity was observed on apilimod at any concentration tested (Fig. 3c).
T123 1170-1269 Sentence denotes We then determined whether apilimod could inhibit entry of SARS-CoV-2 S pseudovirions on 293/hACE2.
T124 1270-1385 Sentence denotes As expected, apilimod treatment inhibited entry of SARS-CoV-2 S pseudovirions in a dose dependent manner (Fig. 3d).
T125 1386-1498 Sentence denotes Similar effects were shown when 293/hACE2 cells were treated with YM201636, another PIKfyve inhibitor (Fig. 3e).
T126 1499-1626 Sentence denotes These results suggested that PIKfyve might be a potential general drug target for viruses that enter cells through endocytosis.
T127 1627-1734 Sentence denotes Two pore channel subtype 2 (TPC2) and TRPML1 in lysosome are two major downstream effectors of PI(3,5)P236.
T128 1735-2017 Sentence denotes While blocking TPC2 activity by tetrandrine, an inhibitor for TPC237, decreased entry of SARS-CoV-2 S pseudovirions (Fig. 3f), treatment of cells with 130, a TRPML1 inhibitor, had no effect (Supplementary Fig. 1), indicating that TPC2, not TRPML1, is important for SARS-CoV-2 entry.