Brivudine

Brivudine has been used in herpes zoster (HZ) treatment for years, but the safety and efficacy of brivudine are inconclusive. Here we perform a meta-analysis to assess the efficacy, safety, incidence of postherpetic neuralgia of brivudine.

Data of randomized controlled Trials (RCTS) were obtained from the databases of both English (PubMed, Embase, and Cochrane Library) and Chinese (China National Knowledge Infrastructure, China Science Journal Database, and WanFang Database) literatures from inception to 12 September 2022. Meta-analyses of efficacy and safety of Brivudine for the treatment of herpes zoster for RCTS were conducted.

The analyses included seven RCTS (2095 patients in experimental group and 2076 patients in control group) in the treatment of HZ with brivudine. It suggested that the brivudine group was superior to the control group in terms of efficacy (p = .0002) and incidence of postherpetic neuralgia (p = .04). But the incidence of adverse reactions has no significant difference between the brivudine and the control groups (p = .22). In addition, subgroup analysis of adverse events also showed that brivudine was about the same safety as other modalities in the treatment of HZ (p > .05).

Brivudine is effective for HZ. However, the evidence on the safety of brivudine is insufficient.

Inhibition of virus replication and inflammatory response is important for the treatment of severe COVID-19 patients. RNA-dependent RNA polymerase (RdRp) is indispensable for SARS-CoV-2 replication, and Janus kinase (JAK) 1 inhibitors exert immunosuppressive effects. RdRp/JAK1 dual-target drugs are expected to ameliorate the severity of the COVID-19 disease. The N-terminal nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain of RdRp is a pseudokinase, and it has structural similarities with JAK1. Herein, we evaluated the inhibitory effects of triphosphate forms of 31 nucleoside drugs in the DrugBank database on the NiRAN domain and JAK1 through a combination of theoretical and experimental methods. By analyzing the three properties of 31 nucleoside drugs (total hydrophobic surface area, number of hydrophobic atoms, and molecular weight), these drugs met the application rule of our developed molecular docking with conformer-dependent charges (MDCC). Based on the MDCC method combined with molecular dynamics simulations, Azvudine and Citicoline among these 31 drugs showed stronger predicted binding affinities with the NiRAN domain as well as JAK1 compared to the reference drug Remdesivir. Further experimental verification, including a thermal shift assay and homogeneous time-resolved fluorescence assay, demonstrated that Azvudine was an RdRp-NiRAN/JAK1 dual-target drug. This work provided a previously unexplored mechanism of Azvudine for COVID-19 treatment and proposed a design concept for RdRp-NiRAN/JAK1 dual-target nucleoside drugs.