Antiviral Peptide-Based Conjugates: State of the Art and Future Perspectives
Toni Todorovski1, Daniela Kalafatovic2, David Andreu1
1Department of Medicine and Life Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
Abstract:
Infectious diseases caused by microbial pathogens (bacteria, virus, fungi, parasites) claim millions of deaths per year worldwide and have become a serious challenge to global human health in our century. Viral infections are particularly notable in this regard, not only because humankind is facing some of the deadliest viral pandemics in recent history, but also because the arsenal of drugs to combat the high levels of mutation, and hence the antigenic variability of (mostly RNA) viruses, is disturbingly scarce. Therefore, the search for new antivirals able to successfully fight infection with minimal or no adverse effects on the host is a pressing task. Traditionally, antiviral therapies have relied on relatively small-sized drugs acting as proteases, polymerases, integrase inhibitors, etc. In recent decades, novel approaches involving targeted delivery such as that achieved by peptide-drug conjugates (PDCs) have gained attention as alternative (pro)drugs for tackling viral diseases. Antiviral PDC therapeutics typically involve one or more small drug molecules conjugated to a cell-penetrating peptide (CPP) carrier either directly or through a linker. Such integration of two bioactive elements into a single molecular entity is primarily aimed at achieving improved bioavailability in conditions where conventional drugs are challenged, but may also turn up novel unexpected functionalities and applications. Advances in peptide medicinal chemistry have eased the way to antiviral PDCs, but challenges remain on the way to therapeutic success. In this paper, we review current antiviral CPP-drug conjugates (antiviral PDCs), with emphasis on the types of CPP and antiviral cargo. We integrate the conjugate and the chemical approaches most often applied to combine both entities. Additionally, we comment on various obstacles faced in the design of antiviral PDCs and on the future outlooks for this class of antiviral therapeutics.
Insights
New antiviral peptide-drug conjugates (PDCs) offer a promising strategy against challenging viral infections. These novel therapeutics combine cell-penetrating peptides (CPPs) with antiviral drugs for improved delivery and efficacy.
Area of Science:
- Infectious Diseases and Virology
- Medicinal Chemistry and Drug Delivery
Background:
- Infectious diseases, particularly viral infections, pose a significant global health threat due to high mortality and limited treatment options.
- Existing antiviral drugs face challenges with viral mutation and limited efficacy, necessitating the development of novel therapeutic strategies.
- Traditional antiviral therapies often involve small molecules targeting viral enzymes, but new approaches are needed to overcome drug resistance and improve delivery.
Purpose of the Study:
- To review current advancements in antiviral cell-penetrating peptide-drug conjugates (antiviral PDCs) as a novel therapeutic approach.
- To highlight the types of CPPs and antiviral payloads utilized in these conjugates.
- To discuss the chemical strategies for conjugating CPPs and drugs, and to identify challenges and future prospects for antiviral PDCs.
Main Methods:
- Review of existing literature on antiviral CPP-drug conjugates (antiviral PDCs).
- Emphasis on the characterization of cell-penetrating peptides (CPPs) and antiviral drug components.
- Analysis of chemical conjugation methods and their impact on conjugate functionality.
Main Results:
- Antiviral PDCs integrate CPPs and antiviral drugs to enhance bioavailability and potentially introduce new therapeutic functionalities.
- Advances in peptide medicinal chemistry facilitate the development of these conjugates, though challenges in design and application persist.
- The review categorizes different CPPs and antiviral cargoes used in conjugate development.
Conclusions:
- Antiviral PDCs represent a promising frontier in combating viral diseases, offering improved drug delivery and efficacy.
- Further research and development are crucial to overcome existing obstacles and realize the full therapeutic potential of antiviral PDCs.
- This class of therapeutics holds significant promise for addressing the urgent need for effective antiviral treatments.
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