Depurination of plant ribosomes by pokeweed antiviral protein

The contamination of important agricultural products such as wheat, barley, or maize with the trichothecene mycotoxin deoxynivalenol (DON) due to infection with Fusarium species is a worldwide problem. Trichothecenes inhibit protein synthesis by targeting ribosomal protein L3. Pokeweed antiviral protein (PAP), a ribosome-inactivating protein binds to L3 to depurinate the α–sarcin/loop of the large rRNA. Plants transformed with the wild-type PAP show lesions and express very low levels of PAP because PAP autoregulates its expression by destabilizing its own mRNA. We show here that transgenic tobacco plants expressing both the wild-type PAP and a truncated form of yeast L3 (L3δ) are phenotypically normal. PAP mRNA and protein levels are very high in these plants, indicating that L3δ suppresses the autoregulation of PAP mRNA expression. Ribosomes are not depurinated in the transgenic plants expressing PAP and L3δ, even though PAP is associated with ribosomes. The expression of the endogenous tobacco ribosomal protein L3 is up-regulated in these plants and they are resistant to the Fusarium mycotoxin DON. These results demonstrate that expression of an N-terminal fragment of yeast L3 leads to trans-dominant resistance to PAP and the trichothecene mycotoxin DON, providing evidence that both toxins target L3 by a common mechanism.

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Synergistic anti-Newcastle disease virus activity of pokeweed antiviral protein, ribavirin, and guanidine

Canadian Journal of Microbiology ◽

10.1139/w98-053 ◽

1998 ◽

Vol 44 (7) ◽

pp. 702-705 ◽

Cited By ~ 1

Author(s):

Eric Weaver ◽

Gary M Aron

Keyword(s):

Newcastle Disease Virus ◽

Key Words ◽

Disease Virus ◽

Newcastle Disease ◽

Pokeweed Antiviral Protein ◽

Antiviral Protein ◽

Virus Activity

Pokeweed antiviral protein (PAP), in combination with either guanidine or ribavirin, exhibited both synergy and antagonism toward the replication of Newcastle disease virus. Low, medium, and high effective concentrations of both PAP and guanidine were synergistic when used in combination. High effective concentrations of ribavirin in combination with PAP were antagonistic, whereas low and medium effective concentrations were synergistic. Key words: pokeweed antiviral protein, Newcastle disease virus, ribavirin, guanidine, synergy.

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Novel Binding Mechanisms of Fusion Broad Range Anti-Infective Protein Ricin A Chain Mutant-Pokeweed Antiviral Protein 1 (RTAM-PAP1) against SARS-CoV-2 Key Proteins in Silico

Toxins ◽

10.3390/toxins12090602 ◽

2020 ◽

Vol 12 (9) ◽

pp. 602

Author(s):

Yasser Hassan ◽

Sherry Ogg ◽

Hui Ge

Keyword(s):

In Silico ◽

Protein Structures ◽

Ligand Docking ◽

Pokeweed Antiviral Protein ◽

Antiviral Protein ◽

Ricin A Chain ◽

In Silico Docking ◽

A Chain ◽

Binding Mechanisms ◽

Ricin A

The deadly pandemic named COVID-19, caused by a new coronavirus (SARS-CoV-2), emerged in 2019 and is still spreading globally at a dangerous pace. As of today, there are no proven vaccines, therapies, or even strategies to fight off this virus. Here, we describe the in silico docking results of a novel broad range anti-infective fusion protein RTAM-PAP1 against the various key proteins of SARS-CoV-2 using the latest protein-ligand docking software. RTAM-PAP1 was compared against the SARS-CoV-2 B38 antibody, ricin A chain, a pokeweed antiviral protein from leaves, and the lectin griffithsin using the special CoDockPP COVID-19 version. These experiments revealed novel binding mechanisms of RTAM-PAP1 with a high affinity to numerous SARS-CoV-2 key proteins. RTAM-PAP1 was further characterized in a preliminary toxicity study in mice and was found to be a potential therapeutic candidate. These findings might lead to the discovery of novel SARS-CoV-2 targets and therapeutic protein structures with outstanding functions.

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