Insights into the role of the cobalt(III)-thiosemicarbazone complex as a potential inhibitor of the Chikungunya virus nsP4

Abstract

Chikungunya virus (CHIKV) is the causative agent of chikungunya fever, a disease that can result in disability. Until now, there is no antiviral treatment against CHIKV, demonstrating that there is a need for development of new drugs. Studies have shown that thiosemicarbazones and their metal complexes possess biological activities, and their synthesis is simple, clean, versatile, and results in high yields. Here, we evaluated the mechanism of action (MOA) of a cobalt(III) thiosemicarbazone complex named [Co III (L 1 ) 2 ]Cl based on its in vitro potent antiviral activity against CHIKV previously evaluated (80% of inhibition on replication) . Furthermore, the complex has no toxicity in healthy cells, as confirmed by infecting BHK-21 cells with CHIKV- nanoluciferase in the presence of the compound, showing that [Co III (L 1 ) 2 ]Cl inhibited CHIKV infection with the selective index of 3.26. [Co III (L 1 ) 2 ]Cl presented a post-entry effect on viral replication, emphasized by the strong interaction of [Co III (L 1 ) 2 ]Cl with CHIKV non-structural protein 4 (nsP4) in the microscale thermophoresis assay, suggesting a potential mode of action of this compound against CHIKV. Moreover, in silico analyses by molecular docking demonstrated potential interaction of [Co III (L 1 ) 2 ]Cl with nsP4 through hydrogen bonds, hydrophobic and electrostatic interactions. The evaluation of ADME-Tox properties showed that [Co III (L 1 ) 2 ]Cl presents appropriate lipophilicity, good human intestinal absorption, and has no toxicological effect as irritant, mutagenic, reproductive, and tumorigenic side effects. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s00775-022-01974-z.

Adopting complementary and integrative medicine: Effects of Antox® and Bactofort® administrations on clinico-pathological changes in pullets inoculated with a very virulent infectious bursal disease virus

“…This might be due to the minerals (such as zinc, magnesium, manganese, copper, cobalt amongst others) present in Antox ® . Zinc and magnesium were reported to play essential role in the modulation of the immune system and interferon (IFN) signaling pathway thus regulating antiviral immunity [34,35] manganese suggested to be capable of inducing interferon production [36] while copper and cobalt inhibits viral replication [37,38]. The antiviral actions of these minerals singly and/or in synergy might be responsible for the better ameliorative effects observed with Antox ® compared to with Bactofort ® .…”

Thermophoretic Assay for Biosensing

“…First, the most widespread is the use of thermophoresis, mainly MST, for reaction affinity assays. [109][110][111][112][113][114][115][116][117][118][119][120][121][122][123][124][125][126] MST technology has unique advantages in the detection of the interaction between molecules and determining their affinity. The determination of MST not only boasts high accuracy [127] and high sensitivity [128] but it can also measure molecular reactions in microliter solutions, identify the reaction sites, [129,130] and determine the affinity of competing reactions.…”