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Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

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Nucleoside-Analog Reverse-Transcriptase Inhibitors (NRTIs) Against Multiple Sclerosis: Comprehensive Review on a

Alfonso Martinisi¹, Paolo Paganetti²

¹Faculty of Economics, Università della Svizzera Italiana (USI), 6900 Lugano, Switzerland.

Neurology International

|May 26, 2026

Summary

Human Endogenous Retroviral sequences, particularly the HERV-W envelope protein, are implicated in multiple sclerosis. Nucleoside-analog Reverse Transcriptase Inhibitors show promise for targeting HERV-W and promoting remyelination.

Keywords:

HERV NRTI antiretrovirals multiple sclerosis remyelination

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Area of Science:

Neuroimmunology
Virology
Genetics

Background:

The precise cause of multiple sclerosis (MS), a neurodegenerative autoimmune disorder, remains incompletely understood.
Growing evidence links Epstein-Barr Virus (EBV) infection to MS incidence, suggesting potential antiviral therapeutic strategies.
Human Endogenous Retroviral (HERV) sequences are increasingly recognized for their role in neurological diseases.

Purpose of the Study:

To review the literature on the role of HERV sequences in MS pathogenesis, focusing on impaired remyelination.
To investigate the HERV-W envelope protein as a potential therapeutic target in MS.
To evaluate the efficacy of antiretroviral drugs in MS treatment and propose Nucleoside-analog Reverse Transcriptase Inhibitors (NtRTIs) as a targeted therapy.

Main Methods:

Literature review of studies on HERV sequences and MS.
Analysis of clinical data from MS patients treated with antiretroviral drugs.
Examination of the role of HERV-W envelope protein in MS pathology and remyelination.
Hypothesis formulation for targeted therapy using NtRTIs.

Main Results:

Elevated levels of the HERV-W envelope protein are observed in individuals with MS.
Antiretroviral drugs have shown mixed results in clinical trials for MS.
The HERV-W envelope protein is a key factor in the impairment of remyelination, a major challenge in MS progression.

Conclusions:

HERV sequences, specifically the HERV-W envelope protein, represent a significant factor in MS pathogenesis.
Nucleoside-analog Reverse Transcriptase Inhibitors offer a potential therapeutic strategy by targeting the HERV-W envelope protein.
Targeting HERV-W with NtRTIs may promote remyelination and improve outcomes for MS patients, offering a novel therapeutic perspective.