The development of highly effective antiviral agents has been a major objective in virology and pharmaceutics. Drug repositioning has emerged as a cost-effective and time-efficient alternative approach to traditional drug discovery and development. This new shift focuses on the repurposing of clinically approved drugs and promising preclinical drug candidates for the therapeutic development of host-based antiviral agents to control diseases caused by coronavirus and influenza virus. Host-based antiviral agents target host cellular machineries essential for viral infections or innate immune responses to interfere with viral pathogenesis. This review discusses current knowledge, prospective applications and challenges in the repurposing of clinically approved and preclinically studied drugs for newly indicated antiviral therapeutics.
Repurposing FDA-approved drugs is a time-efficient, cost-effective and safe approach to developing therapeutic drugs for the new indication of treating viral infection. To repurpose an FDA-approved drug, such as anticancer and other agents, researchers still need to go throughin vitro,in vivoand clinical studies to determine the value of a candidate drug for treating IFV and/or CoV diseases.In vitrostudies can identify viral strains to be targeted, determine the host cell range susceptible to viral infection and reveal additional molecular targets specifically for controlling viral infection. The value of host molecular targets can be evaluated by gene knockdown, knockout or mutation via the methods of RNA interference or CRISPR/Cas9.In vivostudies will determine the maximal tolerable doses and adverse effects, efficacy in controlling viral infection and pharmacokinetics of drug concentrations in the plasma to reestablish an effective and safe regimen and protocol for treating IFV and/or CoV diseases. The newin vitroandin vivoresults will be considered with existing data together to design clinical studies for viral diseases.
Inevitably, there are challenges to the repurposing of drugs for antiviral therapeutics. In general, viral infection is an acute pathogenesis that can require higher doses of a repurposed drug than doses used in treating originally targeted chronic diseases for an optimal outcome. Thus, the administration route and toxicity of a repurposed drug need to be carefully determined. Viral infection also results in changes in not only the host’s immune system but also the function of the host’s organs, which could interfere with pharmacological effects of a repurposed drug or cause additional side effects. Thus, it will be beneficial to study combination therapies capable of targeting viral components, modulating cellular machineries and alleviating adverse effects to achieve optimal outcomes of increased antiviral efficacy, reduced viral resistance and minimized toxicity and side effects.
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