Twenty-eight imidazo[1,2-c]pyrimidin-5(6H)-one nucleoside derivatives incorporating a sulfonamide
scaffold with preferable inactivating activities on pepper mild mottle
virus (PMMoV) were designed and synthesized. Then, compound B29 with illustrious inactivating activity against PMMoV was
received on the basis of the three-dimensional quantitative structure–activity
relationship (3D-QSAR) model, with the EC50 of 11.4 μg/mL,
which was superior to ningnanmycin (65.8 μg/mL) and template
molecule B16 (15.3 μg/mL). Furthermore, (1) transmission
electron microscopy (TEM) indicated that B29 could cause
severe fracture of virions; (2) microscale thermophoresis (MST) and
molecular docking further demonstrated that B29 had faintish
binding affinities with PMMoV CPR62A (K
d = 202.84 μM), PMMoV CPL144A (K
d = 141.57 μM), and PMMoV CPR62A,L144A (K
d = 332.06 μM) compared to PMMoV
CP (K
d = 4.76 μM); and (3) western
blot and reverse transcription-quantitative polymerase chain reaction
(RT-qPCR) results of pCB-GFP-PMMoV CPR62A, pCB-GFP-PMMoV
CPL144A, and pCB-GFP-PMMoV CPR62A,L144A were
consistent with MST and confocal. In brief, the above results indicated
that the amino acids at positions 62 and 144 of PMMoV CP might be
the key amino acid sites of B29 acted on.