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

Shi, Jing; He, Hongfu; Liu, Zhengjun; Hu, Deyu

doi:10.1021/acs.jafc.2c02667

Cited by 3 publications

(3 citation statements)

References 36 publications

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“…In addition to its potent ability to inactivate PMMoV, vanisulfane has also been found to exhibit a strong affinity towards PMMoV coat protein. Thus, it has been suggested that vanisulfane could potentially serve as an anti-PMMoV drug, specifically targeting the PMMoV CP (181,183). With the aim of developing an antiviral drug, 34 novel chalcone derivatives comprised of 1,2,4-oxadiazole moiety was synthesized (184), and evaluated their antiviral abilities (TMV, PMMoV, and TSWV) (184).…”

Section: Application Of Antiviral Agentsmentioning

confidence: 99%

Pepper mild mottle virus: a formidable foe of capsicum production—a review

Kumari,

Sharma,

Patel

et al. 2023

Front. Virol.

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Viruses are one of the major restraining factors in pepper cultivation globally. Among different viruses, pepper mild mottle virus (PMMoV) is one of the most detrimental plant viruses infecting Capsicum spp. belonging to the genus Tobamovirus and Virgaviridae family. It has a monopartite positive-sense single-stranded RNA genome of 6.35 kb size. On an average, PMMoV results in 15%–40% losses in capsicum fruit yield. However, the incidence of PMMoV can reach as high as 95%, leading to substantial yield losses ranging from 75% to 95%. The virus is transmitted via contact, soil, and seeds rather than via insect vectors. PMMoV, because of its seed-borne nature, now occurs worldwide. PMMoV mainly infects Capsicum spp. under natural conditions; however, it can experimentally be transmitted to other plants species belonging to the families Solanaceae, Cucurbitaceae, Labiatae, Chenopodiaceae, and Plantaginaceae. The resistance to tobamoviruses in capsicum is conferred by L locus. Mutations in the coat protein of PMMoV are responsible for the emergence of L-mediated resistance-breaking pathotypes. The highly contagious nature of the virus, seed transmission behavior, and the emergence of virulence complicate its management through a single approach. Therefore, efforts are directed towards providing a more practical and efficient integrated management solution using the RNA interference approach; exploitation of the L gene for resistance breeding; and the inhibitory potential of natural products, systemic resistance-inducing antagonistic bacteria, and chemically synthesized silver nanoparticles. Markers linked to L alleles have been observed to accelerate capsicum breeding programs through marker-assisted selection. In this study, an attempt has been made to compile the recent developments in PMMoV biology, pathogenic variability, genomic organization, and management strategies.

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Section: Application Of Antiviral Agentsmentioning

confidence: 99%

Pepper mild mottle virus: a formidable foe of capsicum production—a review

Kumari,

Sharma,

Patel

et al. 2023

Front. Virol.

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“…35−37 Besides, viral CP has been shown to contribute significantly to the determination of the host range of Tobamoviruses, so it can be used as a potential target for antiviral agent screening. 38 Our group previously designed and synthesized 32 cytidine derivatives containing sulfonamide moieties with significant inhibitory activities against PMMoV, 28 and further omics studies indicated that the protective activity of compound A32 on PMMoV might be consistent with the upregulation of proteins in carbon fixation with photosynthetic organisms. However, modification of the sulfonamide structural unit and preliminary mechanism of action studies are not sufficient; it is urgently needed to further modify the position 8 of imidazo[1,2-c]pyrimidin-5(6H)-one to further investigate its possible mechanism of action in depth on top of obtaining highly active target compounds (Figure 1).…”

Section: ■ Introductionmentioning

confidence: 99%

“…In addition to the basic function of wrapping the viral nucleic acid to protect the viral genetic material from external damage, the CP of plant viruses also has other functions to regulate the relationship between plants and viruses. For example, the CP is associated with virus formation, invasion, systemic movement, and replication. − Besides, viral CP has been shown to contribute significantly to the determination of the host range of Tobamoviruses , so it can be used as a potential target for antiviral agent screening …”

Section: Introductionmentioning

confidence: 99%

Inactivating Activities and Mechanism of Imidazo[1,2-c]pyrimidin-5(6H)-one Nucleoside Derivatives Incorporating a Sulfonamide Scaffold

Yang

Song

Yin

et al. 2023

J. Agric. Food Chem.

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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.

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