Tobacco
mosaic virus coat protein (TMV CP) plays an important role
in viral replication, translation, and intracellular and intercellular
movements. Thus, TMV CP could be regarded as a potential target for
antiviral agents. In this study, in order to find out whether dithioacetal
derivatives act on the CP target, a series of dithioacetal derivatives
containing sulfonamide moiety was first designed and synthesized.
Bioassay results demonstrated that
Y14
,
Y18
, and
Y21
exhibited excellent activities against TMV,
with half-maximal effective concentrations (EC
50
) of the
curative, protective, and inactivate activities being 183.0 ±
3.2, 252.3 ± 2.6, and 63.8 ± 1.2 μg/mL, 270.6 ±
3.7, 249.7 ± 3.5, and 57.7 ± 1.4 μg/mL, and 329.5
± 1.5, 269.2 ± 3.7, and 48.1 ± 2.0 μg/mL for
Y14
,
Y18
, and
Y21
, respectively,
which were higher than those for the control agents ningnanmycin (331.0
± 2.8, 271.0 ± 2.8, and 77.4 ± 1.3 μg/mL, respectively)
and
d2
(471.5 ± 1.4, 447.2 ± 2.1, and 91.7
± 1.8 μg/mL, respectively). Transmission electron microscopy
showed that the particle morphology of TMV was destroyed by
Y21
, and microscale thermophoresis (MST) showed that
Y21
bonded to CP with a dissociation constant (
K
d
) of 9.7 ± 1.7 μM. Then, molecular docking
and MST further illustrated that
Y21
had a weak binding
affinity with the TMV mutant protein (
K
d
= 561.3 ± 83.2 μM). Thus, we deduced that the dithioacetal
derivative
Y21
may inhibit TMV activity by binding TMV
CP. This work provides some new insights for the design and optimization
of novel anti-TMV agents.