Strategy, Progress, and Challenges of Drug Repurposing for Efficient Antiviral Discovery

Abstract

Emerging or re-emerging viruses are still major threats to public health. Prophylactic vaccines represent the most effective way to prevent virus infection; however, antivirals are more promising for those viruses against which vaccines are not effective enough or contemporarily unavailable. Because of the slow pace of novel antiviral discovery, the high disuse rates, and the substantial cost, repurposing of the well-characterized therapeutics, either approved or under investigation, is becoming an attractive strategy to identify the new directions to treat virus infections. In this review, we described recent progress in identifying broad-spectrum antivirals through drug repurposing. We defined the two major categories of the repurposed antivirals, direct-acting repurposed antivirals (DARA) and host-targeting repurposed antivirals (HTRA). Under each category, we summarized repurposed antivirals with potential broad-spectrum activity against a variety of viruses and discussed the possible mechanisms of action. Finally, we proposed the potential investigative directions of drug repurposing.

Kite-Shaped Molecules Block SARS-CoV-2 Cell Entry at a Post-Attachment Step

“…So far, drug therapy has been limited to attempts to reduce the most life-threatening symptoms of the infection that arise due to over-stimulation of the immune response [3]. We therefore lack a first line anti-viral defense to add to the current toolkit [4]. Such first-line treatments would allow more time to develop new vaccines, could improve therapeutics, and might be employed as prophylactics in those who cannot be vaccinated or do not respond well to vaccine.…”

“…Such first-line treatments would allow more time to develop new vaccines, could improve therapeutics, and might be employed as prophylactics in those who cannot be vaccinated or do not respond well to vaccine. Such drugs would ideally target conserved steps in the viral life cycle, be broad-spectrum, and therefore generally applicable to COVID variants of the present and future [4].…”

Aspects of Antiviral Strategies Based on Different Phototherapy Approaches: Hit by the Light

“…The GE therapy research is limited, as there are some difficulties with growing certain viruses and/or specific strains [ 85 ]. There are not so many new antivirals and treatments found, as more attention has been on repurposing drugs [ 86 ], such as nitazoxanide [ 87 , 88 , 89 , 90 , 91 ], rupintrivir, and citrate among others [ 76 , 85 , 92 , 93 , 94 ]. However, none of the potential treatments has been introduced as accepted therapy [ 76 ].…”

Drug Sensitivity of Vaccine-Derived Rubella Viruses and Quasispecies Evolution in Granulomatous Lesions of Two Ataxia-Telangiectasia Patients Treated with Nitazoxanide

“…It is currently unknown whether NTZ can inhibit replication of iVDRV strains. NTZ was shown to be effective against a variety of viruses, but its antiviral mechanisms are not presently clear [ 14 , 15 ]. The drug appears to affect different stages of RuV replication cycle by inhibiting total RNA synthesis in the infected cells and interfering with the trafficking of RuV glycoproteins, E1 and E2 [ 13 ].…”