Drug repurposing process aims to identify new uses for the existing drugs to overcome traditional de novo drug discovery and development challenges. At the same time, as viral infections became a serious threat to humans and the viral organism itself has a high ability to mutate genetically, and due to serious adverse effects that result from antiviral drugs, there are crucial needs for the discovery of new antiviral drugs, and to identify new antiviral effects for the exciting approved drugs towards different types of viral infections depending on the observed antiviral activity in preclinical studies or clinical findings is one of the approaches to counter the viral infections problems. This narrative review article summarized mainly the published preclinical studies that evaluated the antiviral activity of drugs that are approved and used mainly as antibacterial, antifungal, antiprotozoal, and anthelmintic drugs, and the preclinical studies included the in silico, in vitro, and in vivo findings, additionally some clinical observations were also included while trying to relate them to the preclinical findings. Finally, the structure used for writing about the antiviral activity of the drugs was according to the families of the viruses used in the studies to form a better image for the target of antiviral activity of different drugs in the different kinds of viruses and to relate between the antiviral activity of the drugs against different strains of viruses within the same viral family.

The Vinca alkaloid vindoline was coupled at position 17 with several trisubstituted phosphine derivatives and their in vitro anticancer activities on 60 human tumor cell lines (NCI60) were investigated. This phosphonium-type ionic side chain is beneficial because it allows therapeutic molecules to pass through the cell membrane. Thus, the candidates coupled to it can exert their activities in the mitochondria. The coupling of vindoline with the trisubstituted phosphines was achieved through flexible or rigid linkers. Instead of the ionic phosphonium structural part, a neutral moiety, namely the triphenylmethyl group, was also added to the side chain, being sterically similar but without a charge and phosphorus atom. In addition, the triphenylphosphine element was also built at position 10 of vindoline. Most of the derivatives showed low micromolar growth inhibition (GI₅₀) values against most cell lines. Among them, conjugate 9e was outstanding: it exhibited nanomolar anticancer activity on the RPMI-8226 leukemia cell line (GI₅₀ = 20.0 nM). Compound 9g elicited cell cycle disturbance and apoptosis on A2780 ovary cancer cells and inhibited their migration at subantiproliferative concentrations. The selectivity of the conjugates was determined by their effects on non-tumor Chinese hamster ovary (CHO) cells in the CellTiter-Glo Luminescent Cell Viability Assay. Compound 9e showed an estimated half-maximal inhibitory concentration (IC₅₀) value of 1.36 µM, suggesting good selectivity on cancer cells. These results open new perspectives of novel phosphonium-based vindoline derivatives as anticancer compounds.

Drug discovery and development are lengthy and expensive processes that face serious challenges. A new compound must not only produce the desired response with minimal side effects but must also demonstrate better activity than existing drugs. Thus, modification of existing drugs is easier than discovery of new drugs. Furthermore, the rate of development of new antiviral agents has declined significantly in recent decades, and pathogenic viruses have become more serious and have developed resistance against antiviral drugs. Hence, owing to multidrug resistance, severe side effects, and the emergence of new virus types, there is an urgent need for the development of new alternative or synergistic antiviral drugs with minimal side effects. Anti-inflammatory drugs represent a group of drugs with broad clinical applications and remain one of the most widely used medications worldwide. They can relieve the most common symptoms of viral infections (pain and fever). Thus, many researchers have screened for antiviral activities among the marketed anti-inflammatory drugs against different types of viral infections, based on the observed antiviral activity in different preclinical and clinical studies. This mini-review article summarizes preclinical studies (in silico, in vitro, and in vivo) that evaluated the antiviral activity of approved anti-inflammatory drugs.

One of the best-known flavonoid chrysin was coupled at position 7 with several trisubstituted phosphine derivatives with a flexible spacer, and their in vitro anticancer activities were investigated on 60 human tumor cell lines (NCI60) and on several gynecological cancer cells. The trisubstituted phosphines contained different substituents on the aromatic ring(s), e.g., methyl and methoxy groups or fluoro atoms. The phosphorus atom was substituted not only with aromatic rings but with cyclohexyl substituents. The ionic phosphonium building block is important because it allows the therapeutic agents to transfer across the cell membrane. Therefore, the pharmacophores linked to it can exert their effects in the mitochondria. Instead of the ionic phosphonium element, a neutral moiety, namely the triphenylmethyl group, was also added to the side chain, being sterically similar but without a charge and phosphorus atom. Most of the hybrids exhibited low micromolar growth inhibition (GI₅₀) values against the majority of the tested cell lines. Notably, conjugate 3f stood out, demonstrating nanomolar antitumor activity against the K-562 leukemia cell line (GI₅₀ = 34 nM). One selected compound (3i) with promising cancer selectivity elicited cell cycle disturbances and inhibited the migration of breast cancer. The tumor-selectivity of 3a and 3f was assessed based on their effects on non-tumor Chinese hamster ovary (CHO) cells using the CellTiter-Glo Luminescent Cell Viability Assay. Given their estimated half-maximal inhibitory concentration (IC₅₀) values on non-tumor CHO cells (2.65 µM and 1.15 µM, respectively), these conjugates demonstrate promising selectivity toward several cancer cell lines. The excellent results obtained may serve as good starting points for further optimization and the design of even more effective flavonoid- and/or phosphonium-based drugs.

Viral enfeksiyonların ortaya çıkması ve yeniden ortaya çıkması, birçoğunun sinir sistemini etkilediği ciddi sorunları temsil eder; bu viral enfeksiyonların birçoğunun hala etkili bir aşı veya tedavisi yoktur, bu nedenle de novo ilaç keşfi yaklaşımı ile birlikte ilacı yeniden tasarlama yaklaşımının dikkate alınması ve başarılı aşıların bulunması bu enfeksiyonların üstesinden gelme çabalarını destekleyecektir. İlacın yeniden kullanım amacına yönelik yaklaşımı ile ilgili olarak, sinir sistemi üzerindeki etkileri onaylanmış ve antiviral aktivite sergileyen ilaçlar, kan-beyin bariyerini geçebilme ve sinir sistemine kolayca ulaşabilme avantajına sahip olarak, yeniden kullanım için umut verici adaylar sunmaktadır. Viral enfeksiyonların üstesinden gelme çabasında yer alan bu anlatı inceleme makalesi, başlangıçta sinir sistemi üzerindeki etkileri için onaylanmış ilaçların antiviral aktivitesine odaklanan araştırmaları özetlemekte ve bulgular viral aile grubuna göre bölümler halinde düzenlenmiştir. Diğer araştırmacılara ilaçların aynı ailenin üyeleri üzerindeki etkisi ile farklı viral ailelerin virüsleri üzerindeki etkisi arasında ilişki kurmasına yardımcı olmak için çalışmalarda kullanılan virüsler.