Abstract
Background: Poor pharmacokinetic profiles and resistance are the main two drawbacks from which currently used antiviral agents suffer, thus make them excellent targets for research, especially in the presence of viral pandemics such as HIV and hepatitis C. Methods: The strategies employed in the studies covered in this review were sorted by the type of drug synthesized into ester prodrugs, targeted delivery prodrugs, macromolecular prodrugs, other nucleoside conjugates, and non-nucleoside drugs. Results: Utilizing the ester prodrug approach a novel isopropyl ester prodrug was found to be potent HIV integrase inhibitor. Further, employing the targeted delivery prodrug zanamivir and valine ester prodrug was made and shown a sole delivery of zanamivir. Additionally, VivaGel, a dendrimer macromolecular prodrug, was found to be very efficient and is now undergoing clinical trials. Conclusions: Of all the strategies employed (ester, targeted delivery, macromolecular, protides and nucleoside analogues, and non-nucleoside analogues prodrugs), the most promising are nucleoside analogues and macromolecular prodrugs. The macromolecular prodrug VivaGel works by two mechanisms: envelope mediated and receptor mediated disruption. Nucleotide analogues have witnessed productive era in the recent past few years. The era of non-interferon based treatment of hepatitis (through direct inhibitors of NS5A) has dawned.
Highlights
Despite the high efficiency of the human immune system, viruses are ubiquitous and versatile organisms with the potential to cause serious illnesses that require aggressive pharmacological intervention, yet existing medicines are by and large inefficient at combatting viruses, making them a target for aggressive exploration to accelerate the development of new antiviral agents.The WHO estimates that there are a total of 36.7 million people living with HIV [1] and 257 million people living with hepatitis B [2]
In light of previously published articles which have reviewed antiviral drug strategies and novel antiviral agents [6,7,8,9,10,11,12], this review aims to explore strategies employed by researchers in the production
As thethe interest behind the applications of macromolecules is not solely forantiviral antiviraldrugs, drugs, the interest behind the applications applications of macromolecules macromolecules is not notlimited solely limited their in the and of agents, and to their to potential in improving the delivery and pharmacokinetics of antiviral agents, and limited to their potential potential in improving improving the delivery delivery and pharmacokinetics pharmacokinetics of antiviral antiviral agents, but due due to the non-specific polymer-charge effect which is exhibited by macromolecules on viruses
Summary
Despite the high efficiency of the human immune system, viruses are ubiquitous and versatile organisms with the potential to cause serious illnesses that require aggressive pharmacological intervention, yet existing medicines are by and large inefficient at combatting viruses, making them a target for aggressive exploration to accelerate the development of new antiviral agents. The WHO estimates that there are a total of 36.7 million people living with HIV [1] and 257 million people living with hepatitis B [2]. These two main infections, as well as pandemics, have urged the scientific community to explore and develop novel and more potent antiviral agents. There are two main approaches to antiviral prodrug design: the traditional or classical approach and the modern one. In light of previously published articles which have reviewed antiviral drug strategies and novel antiviral agents [6,7,8,9,10,11,12], this review aims to explore strategies employed by researchers in the production.
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