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Introduction: Thousands of human infective viruses spread worldwide, yet protective measures exist for only a fraction, with internationally accepted vaccines available for an even smaller subset. Treatment options are limited, often restricted to symptom management, as specific antiviral agents remain elusive for most viruses, including the Sindbis virus. Originating in Africa, Sindbis virus, a member of the Alphavirus genus, is primarily transmitted by arthropod vectors, notably mosquitoes, leading to the manifestation of Sindbis fever characterized by symptoms including rash, headache, joint pain, and fatigue, highlighting its significance as a vector-borne human pathogen. While historically associated with major epidemics in northern European countries such as Ockelbo and Pogosta disease, and Karelian fever, the virus's potential for global spread necessitates vigilance and preparedness for the emergence of outbreaks in new regions. In this context, the exploration of repurposed therapeutics, such as derivatives of glycopeptide antibiotics, holds promise for combating Sindbis virus and other viral pathogens, given their observed antiviral activity against a spectrum of viruses including influenza, Dengue virus, West-Nile virus and Human Immundeficiency virus. Methods: We investigated the antiviral efficacy of 26 synthetic antibiotics and derivatives against Sindbis virus in vitro, using Vero E6 cells. Initial compounds included teicoplanin, ristocetin, and vancomycin and their derivatives. Cytotoxicity assessment preceded evaluation of antiviral potential via microscopic analysis, MTT assay, and quantitative PCR analysis to measure changes in viral copy numbers. Results: Four compounds exhibited potent inhibitory effects, with two demonstrating moderate antiviral activity. Among them, a ristocetine derivative (ERJ-552) displayed exceptional potency against Sindbis virus. Further investigations into its mechanism of action were conducted using a time addition assay to determine its antiviral effects during the infection cycle. Discussion: Our findings underscore the potential of repurposed antibiotics and their derivatives in combating Sindbis virus. The identification of ERJ-552 as a potent antiviral compound highlights avenues for further research into novel therapeutics against alphaviruses and other viral pathogens. The study elucidates the importance of exploring existing drugs for new applications in viral therapy. Conclusion: In conclusion, our study demonstrates the antiviral efficacy of synthetic antibiotics and derivatives against Sindbis virus, with ERJ-552 emerging as a particularly promising candidate. These findings contribute to the ongoing efforts to develop effective treatments against emerging viral pathogens, emphasizing the significance of repurposing existing drugs in the fight against infectious diseases.

Background/Introduction: Zika virus (ZIKV), a member of the Flaviviridae family, causes significant public health concerns. However, Zika virus (ZIKV) symptoms are usually similar to the flu, but it can sometimes cause serious brain-related health problems like meningitis and Guillain-Barre syndrome. It's especially dangerous for pregnant women because it can lead to severe brain defects in fetus, such as microcephaly. There is no vaccine and special treatment against ZIKV. The development of safe methods for virus inactivation is crucial for both research and therapeutic purposes. This study investigates the efficacy of UV-C irradiation in inactivating ZIKV while preserving its immunogenic properties. Methods & Materials: We utilized a specially designed enclosed system allowing selective exposure of ZIKV to UV-C light at 254 nm. The minimum irradiation time required to prevent viral replication was determined using a TCID50 assay. Further characterization of the inactivated virus was performed through immunofluorescence, labeling the viral NS1 protein and dsRNA, and qRT-PCR to assess genomic integrity. Results: UV-C irradiation for 45 seconds effectively inactivated ZIKV with no detectable cytopathic effect. The absence of cytopathic effects post-irradiation confirms the viral replication halt. qRT-PCR confirmed no significant changes in cycle quantification values, indicating preservation of the viral genome's integrity. Confocal microscopy demonstrated that the inactivated virus could enter cells but did not replicate. Discussion: The UV-C inactivation method preserves ZIKV's protein structure and biological activity, making it safe for use in vaccine development, diagnostic assays, and antiviral research. This technique offers a non-toxic alternative to chemical inactivants, crucial for handling pathogenic viruses in a research setting. Conclusion: With the establishment of UV-C irradiation as a safe and effective method for ZIKV inactivation, we pave the way for new investigations into virus-host interactions and vaccine development without the associated risk of infection. Future research will focus on expanding the applications of UV-inactivated ZIKV in therapeutic and diagnostic contexts and further refining inactivation protocols to enhance disease management strategies.