ArticleMolecular therapy. Nucleic acids2021
Dual inhibition of TMPRSS2 and Cathepsin Bprevents SARS-CoV-2 infection in iPS cells.
Article in Molecular therapy. Nucleic acids, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed, 57 citations in OpenAlex.
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- SARS-CoV-2 infection in hiPSC-derived neurons is cathepsin-dependent and causes differential accumulation of HIF1ɑ and phosphorylated tau.Molecular therapy. Nucleic acids · 2025Article
- Monoclonal antibodies against human TMPRSS2 prevent infection by any SARS-CoV-2 variant.iScience · 2025Article
- Cathepsins in cellular entry of human pathogenic viruses.Journal of virology · 2025Review
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- In-cell bioluminescence resonance energy transfer (BRET)-based assay uncovers ceritinib and CA-074 as SARS-CoV-2 papain-like protease inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- A novel multitargeted self-assembling peptide-siRNA complex for simultaneous inhibition of SARS-CoV-2-host cell interaction and replication.Molecular therapy. Nucleic acids · 2024Article
- Coordination chemistry suggests that independently observed benefits of metformin and ZnBiometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2024Article
- A viral assembly inhibitor blocks SARS-CoV-2 replication in airway epithelial cells.Communications biology · 2024Article
- Functional dissection of the spike glycoprotein S1 subunit and identification of cellular cofactors for regulation of swine acute diarrhea syndrome coronavirus entry.Journal of virology · 2024Article
- The use of human iPSC-derived alveolar organoids to explore SARS-CoV-2 variant infections and host responses.Journal of medical virology · 2024Article
- Structure-based discovery of dual pathway inhibitors for SARS-CoV-2 entry.Nature communications · 2023Article
- Prospecting native and analogous peptides with anti-SARS-CoV-2 potential derived from the trypsin inhibitor purified from tamarind seeds.Arabian journal of chemistry · 2023Article
- The S2 Subunit of Infectious Bronchitis Virus Affects Abl2-Mediated Syncytium Formation.Viruses · 2023Article
- A Novel Viral Assembly Inhibitor Blocks SARS-CoV-2 Replication in Airway Epithelial Cells.Research square · 2023Article
- In Vitro and In Vivo Therapeutic Potential of 6,6'-Dihydroxythiobinupharidine (DTBN) fromInternational journal of molecular sciences · 2023Article
- Identification of diphenylurea derivatives as novel endocytosis inhibitors that demonstrate broad-spectrum activity against SARS-CoV-2 and influenza A virus both in vitro and in vivo.PLoS pathogens · 2023Article
- Article
- Identification of Z-Tyr-Ala-CHNMicroorganisms · 2023Article
- Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It has been reported that many receptors and proteases are required for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Although angiotensin-converting enzyme 2 (ACE2) is the most important of these receptors, little is known about the contribution of other genes. In this study, we examined the roles of neuropilin-1, basigin, transmembrane serine proteases (TMPRSSs), and cathepsins (CTSs) in SARS-CoV-2 infection using the CRISPR interference system and ACE2-expressing human induced pluripotent stem (iPS) cells. Double knockdown of TMPRSS2 and cathepsin B (CTSB) reduced the viral load to 0.036% ± 0.021%. Consistently, the combination of the CTPB inhibitor CA-074 methyl ester and the TMPRSS2 inhibitor camostat reduced the viral load to 0.0078% ± 0.0057%. This result was confirmed using four SARS-CoV-2 variants (B.1.3, B.1.1.7, B.1.351, and B.1.1.248). The simultaneous use of these two drugs reduced viral load to less than 0.01% in both female and male iPS cells. These findings suggest that compounds targeting TMPRSS2 and CTSB exhibit highly efficient antiviral effects independent of gender and SARS-CoV-2 variant.
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