Antiviral Activity of Acetylsalicylic Acid against Bunyamwera Virus in Cell Culture.
Sara Yolanda Fernández-SánchezJose Pedro Cerón-CarrascoCristina RiscoIsabel Fernández de CastroPublished in: Viruses (2023)
The Bunyavirales order is a large group of RNA viruses that includes important pathogens for humans, animals and plants. With high-throughput screening of clinically tested compounds we have looked for potential inhibitors of the endonuclease domain of a bunyavirus RNA polymerase. From a list of fifteen top candidates, five compounds were selected and their antiviral properties studied with Bunyamwera virus (BUNV), a prototypic bunyavirus widely used for studies about the biology of this group of viruses and to test antivirals. Four compounds (silibinin A, myricetin, L-phenylalanine and p-aminohippuric acid) showed no antiviral activity in BUNV-infected Vero cells. On the contrary, acetylsalicylic acid (ASA) efficiently inhibited BUNV infection with a half maximal inhibitory concentration (IC 50 ) of 2.02 mM. In cell culture supernatants, ASA reduced viral titer up to three logarithmic units. A significant dose-dependent reduction of the expression levels of Gc and N viral proteins was also measured. Immunofluorescence and confocal microscopy showed that ASA protects the Golgi complex from the characteristic BUNV-induced fragmentation in Vero cells. Electron microscopy showed that ASA inhibits the assembly of Golgi-associated BUNV spherules that are the replication organelles of bunyaviruses. As a consequence, the assembly of new viral particles is also significantly reduced. Considering its availability and low cost, the potential usability of ASA to treat bunyavirus infections deserves further investigation.
Keyphrases
- induced apoptosis
- low cost
- sars cov
- cell cycle arrest
- electron microscopy
- poor prognosis
- endoplasmic reticulum stress
- heart rate
- signaling pathway
- human health
- healthcare
- cell death
- high glucose
- high resolution
- gram negative
- drug induced
- oxidative stress
- resistance training
- pi k akt
- long non coding rna
- endoplasmic reticulum
- genetic diversity