Recent Trends and Spotlight on Nucleotide-Based Drugs: Novel Targets, their Design, Delivery, and Clinical Potential

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About this Research Topic

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Background

Nucleotide-based drugs make up a large class of drugs which have clinical applications against diverse types of diseases and disorders. Structurally, drugs of this class mimic the naturally occurring nucleotides, which incorporate in the genetic material and ultimately leads to the termination of the chain. Anti-viral efficacy of this class is well known with clinical approved candidates against a diverse type of viruses like HIV-1, Varicella-Zoster (VZV), cytomegalovirus (CMV), herpes simplex virus (HSV) and hepatitis C virus (HCV). Recently, a few drug candidates have also been approved against the SARS COV-2 like Fevipiravir, Remdesivir and Molunapiravir.

Several clinically approved anti-cancer drugs belong to this category, such as: cytarabine, gemcitabine, mercaptopurine, azacytidine, cladribine, decitabine, fluorouracil, floxuridine, fludarabine, and nelarabine. Drugs of this class have also been approved for other uses like anti-bacterial (trimethoprim) and rheumatologic diseases (azathioprine and allopurinol)

Recently, oligonucleotides are an emerging new class of therapeutics, targeting disease at the genetic level by preventing the expression of disease causing proteins or the silencing of certain genes. Oligonucleotides comprise of subcategories like antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), small hairpin RNAs (shRNAs), anti-micro RNAs (anti-miRs) and aptamers.
Structural heterogeneity of nucleosides (including oligonucleotides), their delivery, selectivity, cellular uptake, post-delivery activation, metabolic stability and other pharmacokinetic parameters are continuous interesting research areas.

The current topic is aiming to collect quality publications, covering some intriguing potential of nucleotide-based drugs against the newly emerging infectious diseases as well as dysregulated molecular pathways responsible for clinical physiological disorders like cancer, diabetes, and Parkinsonian disease.

Special emphasis is given to the translational potential of emerging oligonucleotides, due to their unprecedentedly therapeutic applications in different diseases like macular degeneration, veno-occlusive disease, muscular dystrophy, polyneuropathy and porphyria.

Furthermore, we are also aiming to involve publications on, but not limited to:
• Druggable targets
• Recent strategies in their delivery
• In-depth discussion on the prodrug based strategies
• Synthetic conjugates
• Recent advances using nanocarrier based drug delivery system and target/site specific drug delivery systems.

Authors can submit research and review studies relevant to nucleotide-based drugs (including nucleoside and Oligonucleotides) with special emphasis on recent advances in the areas like novel targets, mechanistic aspects, designing strategies, clinical applications, repurposing against newer indications, possible therapeutic potential, and future prospective.

High quality studies focusing on their delivery including targeted delivery using nanocarriers systems, prodrug designing approaches, chemical modification, bioconjugation and other approaches in tailoring their pharmacokinetic profile and pharmacological response.

Keywords: Nucleotide, Prodrug, Pharmacology, Targeted delivery, Pharmacokinetic

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