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. |