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11:43
Procedures for the Identification of SARS-CoV-2 Entry Inhibitors as Potential Antivirals using MLV-Based Pseudoviruses
Published on: February 27, 2026
Targeted IL-27-based gene therapy in preventing SARS-CoV-2 entry.
Grace E Mulia1,2, Janelle E Salameh1,3, Marxa L Figueiredo4,5
1Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue Institute for Drug Discovery, Purdue University, 625 Harrison St, LYNN 2177, West Lafayette, Indiana, 47904, USA.
Molecular Biology Reports
|July 11, 2026
Summary
ACE2-targeted IL-27 gene therapy shows potential for inhibiting SARS-CoV-2 entry by targeting the ACE2 receptor. Further research is needed to optimize this cell-based approach for COVID-19 treatment.
Area of Science:
- Virology
- Gene Therapy
- Cell Biology
Background:
- Coronaviruses (SARS-CoV, SARS-CoV-2) cause severe respiratory illness and global health crises.
- Current treatments for COVID-19 have limitations, especially against viral entry and new variants.
- Angiotensin-converting enzyme 2 (ACE2) is the primary receptor for SARS-CoV-2, making it a key therapeutic target.
Purpose of the Study:
- To explore ACE2-targeted interleukin-27 (IL-27) delivery via stromal cells as a strategy to inhibit SARS-CoV-2 entry.
- To build upon prior success with IL-27 gene therapy for acute respiratory distress syndrome.
Main Methods:
- Developed an in vitro model using SARS-CoV-2 spike pseudotyped lentivirus to simulate viral entry.
- Engineered human adipose-derived stromal cells to deliver either ACE2-targeted or non-targeted IL-27.
- Tested two regimens: pre-treatment and simultaneous addition of conditioned media and virus.
Main Results:
- ACE2-targeted IL-27 demonstrated a trend toward reduced lentiviral entry in a concentration-dependent manner.
- The effect was more pronounced in A549-ACE2 cells, though statistical significance was not reached.
- Viral entry was quantified using luciferase reporter activity and genome copy units.
Conclusions:
- Provides proof-of-concept for ACE2-targeted IL-27 stromal cell-based gene therapy to inhibit SARS-CoV-2 entry.
- Further optimization of delivery, dosing, and testing against viral replication, inflammation, and variants is necessary.
- This approach may serve as an adjunct therapy for COVID-19.
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