Discovery of Novel Chromone Derivatives as Potential Anti-TSWV Agents

Abstract

A series of novel chromone derivatives containing dithioacetals were prepared, and their antiviral activity against tomato spotted wilt virus (TSWV) was studied. The results showed that compounds A1−A31 had good inhibitory activity against TSWV. The 3D-QSAR model was built to analyze the structure−activity relationship of the compounds. We further found that compounds A32 and A33 had excellent anti-TSWV activities based on the results of 3D-QSAR, which were better than the control agents ningnanmycin and ribavirin. To study the mode of action of these compounds on TSWV, the nucleocapsid protein of TSWV (TSWV N) was cloned, expressed, and purified in the study. The results of the microscale thermophoresis (MST) experiments indicate that compound A33 can better bind with TSWV N. The molecular docking experiment further indicated that the mode of action of the compound A33 is to inhibit the virus by blocking the combination of TSWV N and viral RNA. Therefore, this study has found that chromone compound A33 is a potential anti-TSWV agent that targets TSWV N.

Pepper Mild Mottle Virus Coat Protein as a Novel Target to Screen Antiviral Drugs

“…The inactivation activity of the compound mainly destroys the structure of the virus to prevent the virus from infecting the host. 33 As shown in Figure 7, the affinity between CP and vanisulfane was mainly determined, and the lowest (A3) and highest (C4, except vanisulfane) and COS in the dithioacetal series were selected from the inactivation activity screening as controls. According to the data, the affinity between vanisulfane (Figure 7A) and CP was the best (K d = 6.49 μM, EC 50 = 152.8 μg/mL), which was better than C4 (K d = 18.44 μM, EC 50 = 192.9 μg/mL) (Figure 7B), A3 (K d = 188.11 μM, EC 50 = NA) (Figure 7C), and COS (K d = 82.23 μM, EC 50 = 1668.6 μg/mL) (Figure 7D).…”

“…Microscale thermophoresis (MST) can quickly detect a wide range of interactions involving large and complex biomolecules . A Monolith NT Protein Labeling Kit RED-NHS (Amine Reactive) was used to label the target proteins (PMMoV CP) with a desalting column according to the manufacturer’s instructions . Experiments were conducted with a Monolith NT.115 instrument (Nano Temper Technologies, München, Germany).…”

Recent Research Progress: Discovery of Anti-Plant Virus Agents Based on Natural Scaffold

“…The curative and protective EC 50 values of compound 24 against TSWV were 124.2 and 109.3 gm/L, respectively. It may exert antiviral activity by blocking the binding of TSWV N to viral RNA ( Zan et al, 2021 ). At a concentration of 500 mg/L, compound 25 exhibited good curative, protective and inactivating activities against TMV, which were 68.8, 58.8, and 86.0%, respectively.…”

Design, Synthesis, and Biological Activity of Novel Chalcone Derivatives Containing an 1,2,4-Oxadiazole Moiety

“…N. glutinosa L. was used as a local lesion host to evaluate the antiviral activity against TMV, PMMoV, and TSWV when the plants grew to 5-6 leaf stages. TMV, PMMoV, and TSWV were purified by the Gooding method (Gooding and Hebert, 1967) and the curative, protective activities of compounds were performed with the reported methods at 500 μg/ml (Song, et al, 2005;Zan, et al, 2021;Shi, et al, 2022). The EC 50 values of the antiviral activity at concentrations of 500, 250, 125, 62.5, and 31.25 μg/ml were then calculated.…”