Title |
An off-target effect of BX795 blocks herpes simplex virus type 1 infection of the eye
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Published in |
Science Translational Medicine, February 2018
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DOI | 10.1126/scitranslmed.aan5861 |
Pubmed ID | |
Authors |
Dinesh Jaishankar, Abraam M Yakoub, Tejabhiram Yadavalli, Alex Agelidis, Neel Thakkar, Satvik Hadigal, Joshua Ames, Deepak Shukla |
Abstract |
Herpes simplex virus type 1 (HSV-1) causes recurrent mucocutaneous lesions in the eye that may advance to corneal blindness. Nucleoside analogs exemplified by acyclovir (ACV) form the primary class of antiherpetic drugs, but this class suffers limitations due to the emergence of viral resistance and other side effects. While studying the molecular basis of ocular HSV-1 infection, we observed that BX795, a commonly used inhibitor of TANK-binding kinase 1 (TBK1), strongly suppressed infection by multiple strains of HSV-1 in transformed and primary human cells, cultured human and animal corneas, and a murine model of ocular infection. Our investigations revealed that the antiviral activity of BX795 relies on targeting Akt phosphorylation in infected cells, leading to the blockage of viral protein synthesis. This small-molecule inhibitor, which was also effective against an ACV-resistant HSV-1 strain, shows promise as an alternative to existing drugs and as an effective topical therapy for ocular herpes infection. Collectively, our results obtained using multiple infection models and virus strains establish BX795 as a promising lead compound for broad-spectrum antiviral applications in humans. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United Kingdom | 6 | 15% |
Saudi Arabia | 3 | 7% |
Canada | 2 | 5% |
Puerto Rico | 1 | 2% |
Malaysia | 1 | 2% |
Mexico | 1 | 2% |
Russia | 1 | 2% |
Germany | 1 | 2% |
Other | 3 | 7% |
Unknown | 13 | 32% |
Demographic breakdown
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Members of the public | 32 | 78% |
Scientists | 8 | 20% |
Practitioners (doctors, other healthcare professionals) | 1 | 2% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 48 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Bachelor | 10 | 21% |
Student > Ph. D. Student | 7 | 15% |
Student > Master | 5 | 10% |
Student > Postgraduate | 5 | 10% |
Researcher | 5 | 10% |
Other | 6 | 13% |
Unknown | 10 | 21% |
Readers by discipline | Count | As % |
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Agricultural and Biological Sciences | 8 | 17% |
Immunology and Microbiology | 6 | 13% |
Medicine and Dentistry | 5 | 10% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 6% |
Other | 7 | 15% |
Unknown | 11 | 23% |