ArticlePLoS neglected tropical diseases2017
The phosphatidylinositol-3-phosphate 5-kinase inhibitor apilimod blocks filoviral entry and infection.
Article in PLoS neglected tropical diseases, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 117 citations in OpenAlex.
- Synthesis and evaluation of 3,5-disubstituted isothiazolo[4,5-b]pyridines, pyrazolo[4,3-b]pyridines and isothiazolo[3,4-b]pyrazines as inhibitors of PIKfyve.Bioorganic chemistry · 2026Article
- Host soluble inositol phosphate signaling promotes coronavirus replication.bioRxiv : the preprint server for biology · 2026Article
- Reciprocal control of viral infection and phosphoinositide dynamics.FEBS letters · 2026Review
- PIKfyve preserves endolysosomal function in photoreceptors and RPE cells to maintain retinal integrity.Cell death & disease · 2026Article
- How endosomal PIKfyve inhibition prevents viral membrane fusion and entry.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Endolysosomal trafficking regulator SH-BC-893 inhibits coronavirus entry in vitro and in vivo.Scientific reports · 2026Article
- PIKfyve mediates the maturation of mycobacteria-containing vesicles.Frontiers in cellular and infection microbiology · 2026Article
- Phosphoinositide kinase PIKfyve inhibitor apilimod blocks hepatitis E virus infection.eGastroenterology · 2026Article
- Synthesis, structure-activity relationships, and SARS-CoV-2 antiviral activity of 3,5-disubstituted isothiazolo[4,3-Frontiers in chemistry · 2026Article
- How endosomal PIKfyve inhibition prevents viral membrane fusion and entry.bioRxiv : the preprint server for biology · 2025Article
- Structure-Activity Relationship Study of 3-Alkynyl-6-aryl-isothiazolo[4,3-Pharmaceuticals (Basel, Switzerland) · 2025Article
- Development of a Second-Generation,Journal of medicinal chemistry · 2025Article
- Inhibition of early EHDV2-Ibaraki infection steps in bovine cells by endosome alkalinization or ikarugamycin, but not by blockage of individual endocytic pathways.Frontiers in cellular and infection microbiology · 2025Article
- A PIKfyve modulator combined with an integrated stress response inhibitor to treat lysosomal storage diseases.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A dual inhibitor of PIP5K1C and PIKfyve prevents SARS-CoV-2 entry into cells.Experimental & molecular medicine · 2024Article
- Why Certain Repurposed Drugs Are Unlikely to Be Effective Antivirals to Treat SARS-CoV-2 Infections.Viruses · 2024Article
- Two-pore channels regulate endomembrane tension to enable remodeling and resolution of phagolysosomes.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The temporal association of CapZ with early endosomes regulates endosomal trafficking and viral entry into host cells.BMC biology · 2024Article
- Pan-antiviral effects of a PIKfyve inhibitor on respiratory virus infection in human nasal epithelium and mice.Antimicrobial agents and chemotherapy · 2024Article
- Pseudorabies virus inhibits progesterone-induced inactivation of TRPML1 to facilitate viral entry.PLoS pathogens · 2024Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 2 institutions in 2 countries.
Funding
Abstract
Phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) is a lipid kinase involved in endosome maturation that emerged from a haploid genetic screen as being required for Ebola virus (EBOV) infection. Here we analyzed the effects of apilimod, a PIKfyve inhibitor that was reported to be well tolerated in humans in phase 2 clinical trials, for its effects on entry and infection of EBOV and Marburg virus (MARV). We first found that apilimod blocks infections by EBOV and MARV in Huh 7, Vero E6 and primary human macrophage cells, with notable potency in the macrophages (IC50, 10 nM). We next observed that similar doses of apilimod block EBOV-glycoprotein-virus like particle (VLP) entry and transcription-replication competent VLP infection, suggesting that the primary mode of action of apilimod is as an entry inhibitor, preventing release of the viral genome into the cytoplasm to initiate replication. After providing evidence that the anti-EBOV action of apilimod is via PIKfyve, we showed that it blocks trafficking of EBOV VLPs to endolysosomes containing Niemann-Pick C1 (NPC1), the intracellular receptor for EBOV. Concurrently apilimod caused VLPs to accumulate in early endosome antigen 1-positive endosomes. We did not detect any effects of apilimod on bulk endosome acidification, on the activity of cathepsins B and L, or on cholesterol export from endolysosomes. Hence by antagonizing PIKfyve, apilimod appears to block EBOV trafficking to its site of fusion and entry into the cytoplasm. Given the drug's observed anti-filoviral activity, relatively unexplored mechanism of entry inhibition, and reported tolerability in humans, we propose that apilimod be further explored as part of a therapeutic regimen to treat filoviral infections.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.