# The Impact of the S-Adenosylmethionine Analogue Sinefungin on Viral Life Cycles
## 4 Discussion
Lower concentrations (50 and 25 \(\upmu\)g/mL) resulted in minimal inhibition (reduction \(<\) 0.18 \(\log_{10}\)). At 20 hpi, the inhibition increased, with 200 and 100 \(\upmu\)g/mL producing reductions of 1.82 and 1.77 \(\log_{10}\), respectively, while no significant reduction was observed at 50 or 25 \(\upmu\)g/mL. At 30 hpi, the maximal antiviral activity was observed, with 200 \(\upmu\)g/mL reducing the viral titers by 3.05 \(\log_{10}\) and 100 \(\upmu\)g/mL by \(\sim\)0.91 \(\log_{10}\). Again, lower concentrations showedminimal effects (<0.1 log\({}_{10}\)). For SARS-CoV-2, sinefungin treatment at 6, 12, and 24 hpi also showed a time- and dose-dependent antiviral effect. At 6 hpi, 200 ug/mL reduced the viral titers by 2.17 log\({}_{10}\), while 100 ug/mL achieved a reduction of 0.88 log\({}_{10}\). Concentrations of 50 and 25 ug/mL induced reductions of less than 0.35 log\({}_{10}\). At 12 hpi, the antiviral efficacy significantly increased, with 200 and 100 ug/mL producing reductions of 4.28 and 2.33 log\({}_{10}\), respectively. A comparable reduction of 2.23 log\({}_{10}\) was also observed at 50 ug/mL, while 25 ug/mL was ineffective. At 24 h post-infection, sinefungin showed its strongest antiviral effect: 200 ug/mL reduced the viral yield by 6.18 log\({}_{10}\) and 100 ug/mL reduced it by approximately 5.42 log\({}_{10}\). A reduction of 1.46 log\({}_{10}\) was observed at 50 ug/mL, while 25 ug/mL produced only minimal inhibition (0.06 log\({}_{10}\)). There is limited evidence regarding the antiviral activity of sinefungin. [PERSON] et al. demonstrated an effect of sinefungin on the viral yield following the infection of CRFK cells with Feline Calicivirus (FCV), Feline infectious peritonitis virus (FIPV), FHIV-1, Pseudorabies virus (PRV) and Equine herpes virus type 1 (EHV-1). In response to treatment with 100 ug/mL of sinefungin, the plaque counts for FCV and FIPV were reduced by 67.7% and 7.8%, respectively, compared to those in control infection. In contrast, sinefungin showed greater efficacy against FHV-1, with a plaque reduction of 0.04%. In contrast, PRV and EHV-1, both belonging to the Varicellovirus genus, demonstrated reduced susceptibility to sinefungin, with plaque yields of 52.4% and 21.9%, respectively. The effect of sinefungin on FHV-1 has been extensively studied. The results have shown that sinefungin did not impact the adhesion of FHV-1 to the host cells but could interfere with post-adsorption biochemical processes, with an IC\({}_{50}\) value of 9.5 ug/mL [17]. [PERSON] et al. demonstrated antiviral activity of sinefungin against the smallpox virus, showing significant inhibition of the intracellular phase of infection. At a 200 ug/mL concentration, sinefungin induced a 77% reduction in viral replication. This effect was attributed to the compound's inhibition of guanine-7-methyltransferase, an enzyme crucial for viral RNA methylation, thereby disrupting key processes in the viral life cycle [18]. Moreover, [PERSON] et al. demonstrated that sinefungin acted as an inhibitor of VSV mRNA cap methylation in vitro. Based on this observation, the researchers evaluated its ability to inhibit viral replication. The results revealed a dose-dependent reduction in the viral yield, with an approximate IC\({}_{50}\) of 220 uM [33]. Due to the broad-spectrum antiviral activity of sinefungin and its effect on a critical target involved in different stages of the viral life cycle, this compound has significant potential as a therapeutic agent. Sinefungin inhibits key enzymatic processes, particularly those related to DNA and RNA methylation, a modification essential for genomic stability, protein translation, and the regulation of viral RNA. By targeting these crucial processes, sinefungin impacts a broad spectrum of RNA and DNA viruses, positioning it as a promising candidate for the treatment of various viral infections [34].