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Published on: July 15, 2019
In Vivo and In Vitro Studies Assessing the Antiviral Efficacy of Double Combinations Against Coxsackievirus B
Adelina Stoyanova1, Simeon Galabov1, Vadim Makarov2
1The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
Abstract:
Coxsackievirus B (CVB) infections, ranging from mild to severe diseases, lack specific antiviral treatments, underscoring the need for novel therapeutic strategies. Drug therapy is an important tool for controlling enterovirus infections, but clinically effective drugs do not currently exist, mainly due to the development of drug resistance. Combination therapy with two or more drugs has the potential to successfully inhibit viral infection more effectively than either drug alone as well as delay the development of resistance. This study explores the consecutive alternating administration (CAA) scheme in mice with CVB1 infection, utilizing double antiviral combinations consisting of pleconaril and MDL-860, with guanidine hydrochloride and oxoglaucine. The CAA combinations of pleconaril achieved a survival rate, in infected mice, of up to 59%, while the combinations of MDL-860 showed no significant effects. CAA reduced mortality, prolonged mean survival time (up to 5 days), and mitigated drug resistance compared to monotherapy or simultaneous administration. Monotherapeutic courses and daily administration of double combinations had no effect. Phenotypic characterization using the IC50 marker of virus isolates from brain tissue of infected and treated mice was of particular importance for the evaluation of the CAA treatment scheme. The results show increased susceptibility of the virus isolates to the partner compounds in double CAA combinations. In contrast, virus isolates from the monotherapeutic groups manifested a diminished susceptibility to their respective compound, which signals the development of drug resistance. All data obtained prove the potential of the CAA scheme for the development of effective chemotherapy of enterovirus infections.
Insights
Consecutive alternating administration (CAA) of antiviral drugs for Coxsackievirus B (CVB) infections in mice improved survival and reduced drug resistance. This combination therapy shows promise for treating enterovirus infections.
Area of Science:
- Virology
- Pharmacology
- Infectious Diseases
Background:
- Coxsackievirus B (CVB) infections lack specific antiviral treatments, and existing drugs face resistance challenges.
- Combination therapy offers a strategy to enhance antiviral efficacy and overcome drug resistance.
Purpose of the Study:
- To investigate the efficacy of a consecutive alternating administration (CAA) scheme for treating CVB1 infections in mice.
- To evaluate antiviral drug combinations, including pleconaril and MDL-860, against CVB.
Main Methods:
- Mice with CVB1 infection were treated with double antiviral combinations using a CAA scheme.
- Viral susceptibility was assessed using the IC50 marker in isolates from brain tissue.
- Survival rates and mean survival time were monitored.
Main Results:
- CAA with pleconaril combinations increased survival rates up to 59% and prolonged mean survival time by 5 days.
- CAA mitigated the development of drug resistance compared to monotherapy or simultaneous administration.
- Monotherapy and simultaneous double combination treatments showed no significant effect.
Conclusions:
- The CAA scheme demonstrates potential for effective chemotherapy against enterovirus infections.
- CAA can enhance antiviral efficacy and delay resistance development.
- This therapeutic strategy warrants further investigation for clinical application.
