In vitro effect of some nucleoside reverse transcriptase inhibitors against HSV-1 replication

Area of Science:

• Virology
• Pharmacology
• Molecular Biology

Background:

• Herpes simplex virus type 1 (HSV-1) is a common human pathogen.
• Nucleoside reverse transcriptase inhibitors (NRTIs) are a class of antiviral drugs primarily used to treat HIV.
• The potential of NRTIs against other viral infections, like HSV-1, is an area of ongoing research.

Purpose of the Study:

• To investigate the efficacy of selected nucleoside reverse transcriptase inhibitors (NRTIs) against herpes simplex virus type 1 (HSV-1) infection.
• To evaluate the direct antiviral effects of NRTIs on HSV-1 replication in vitro.

Main Methods:

• In silico prediction of interactions between HSV-1 thymidine kinase and various NRTIs using the SwissTargetPrediction server.
• Assessment of Vero cell viability following treatment with NRTIs using the MTT assay.
• Quantification of HSV-1 replication via quantitative real-time PCR (qPCR) in treated cell supernatants.

Main Results:

• Acyclovir, zidovudine, stavudine, didanosine, and entecavir demonstrated significant reductions in HSV-1 viral titers.
• Viral titer reductions ranged from 19-fold (stavudine) to 44-fold (didanosine).
• The MTT assay confirmed that the tested NRTIs did not adversely affect Vero cell viability at the concentrations used.

Conclusions:

• Nucleoside reverse transcriptase inhibitors (NRTIs) exhibit significant antiviral activity against HSV-1 in cell culture.
• These findings suggest that NRTIs could be potential candidates for further investigation as anti-HSV-1 agents.
• The study highlights the broad-spectrum antiviral potential of certain NRTIs beyond their established use in HIV therapy.