scholarly journals Post-Infection Entry Mechanism of Ricin A Chain-Pokeweed Antiviral Proteins (RTA-PAPs) Chimeras is Mediated by Viroporins

2021 ◽  
Author(s):  
Yasser Hassan
Keyword(s):  
Post Infection ◽  
Chimeric Protein ◽  
Ligand Docking ◽  
Host Cell Membrane ◽  
Ricin A Chain ◽  
Infected Cells ◽  
Antiviral Proteins ◽  
A Chain ◽  
Ricin A

The limitations of virus-specific antiviral drugs became apparent during the current COVID-19 pandemic. The search for broad range antiviral proteins of a new kind to answer current and future pandemics has become an even more pressing matter. Here, the author further describes the expected anti-SARS-CoV-2 mechanisms of a novel broad range antiviral chimeric protein constructed between ricin A chain and pokeweed antiviral proteins. The latest in protein-ligand docking software were used to determine binding affinity of RTA-PAPs to SARS-CoV-2 frameshift stimulation element and elucidate the preferential post-infection entry mechanisms of RTA-PAPs into virus infected cells over non-infected ones, by doing a comparative analysis between in vitro and in silico results on numerous viruses. The results obtained strongly suggest that the post-infection preferential entry of RTA-PAPs into infected cells is mediated by the presence of viroporins integrated into the host cell membrane. The discovery of this mechanism revealed RTA-PAPs, and proteins like them, to be a new class of broad range antivirals that target with high specificity viroporin producing viruses, and with gain of functions in antiviral activities, post-infection.

scholarly journals 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 ◽  
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.

Immunotoxins up to the present day

1989 ◽  
Vol 9 (2) ◽  
pp. 139-156 ◽  
Author(s):  
Francis A. Drobniewski
Keyword(s):  
Clinical Studies ◽  
Polyclonal Antibodies ◽  
Cell Binding ◽  
Ricin A Chain ◽  
Future Role ◽  
A Chain ◽  
Ricin A

Immunotoxins consist of monoclonal or polyclonal antibodies conjugated to bacterial or plant toxins. The toxins used are typically of the A-B type in which a toxic A chain is coupled to a B chain responsible for cell binding and facilitation of A chain entry into the cytosol. Two broad strategies have been followed: coupling intact toxins, or A chains alone, to antibodies. This review examines current progress in in vitro and in vivo research, including recent clinical studies, concentrating principally on ricin or ricin A chain conjugates. The future role of conjugates using membrane-acting toxins, immunolysins, is also discussed.

scholarly journals Cytotoxicity of a cell-reactive immunotoxin containing ricin A chain is potentiated by an anti-immunotoxin containing ricin B chain.

1984 ◽  
Vol 160 (1) ◽  
pp. 341-346 ◽  
Author(s):  
E S Vitetta ◽  
R J Fulton ◽  
J W Uhr
Keyword(s):  
Cell Surface ◽  
Cell Line ◽  
Ricin A Chain ◽  
Daudi Cell ◽  
A Cell ◽  
A Chain ◽  
Ricin A

In vitro killing of the human Daudi cell line by either univalent [F(ab')] or divalent (IgG) forms of rabbit anti-human Ig (RAHIg) coupled to ricin A chain can be specifically potentiated by a "piggyback" treatment with ricin B chain coupled to goat anti-rabbit Ig (GARIg). When cells are treated with univalent immunotoxin (IT) [F(ab') RAHIg-A] and then cultured, IT can be detected on the cell surface for at least 5 h, since GARIg-B can still enhance killing at this time. These results provide a strategy for in vivo use of A chain- and B chain-containing IT.

scholarly journals Novel anti-SARS-CoV-2 mechanisms of fusion broad range anti- infective protein ricin A chain mutant-pokeweed antiviral protein 1 (RTAM-PAP1) in silico

2020 ◽  
Author(s):  
Yasser Hassan ◽  
Sherry Ogg ◽  
Hui Ge
Keyword(s):  
In Silico ◽  
Protein Structures ◽  
Ligand Docking ◽  
Pokeweed Antiviral Protein ◽  
Antiviral Protein ◽  
Ricin A Chain ◽  
High Affinity ◽  
A Chain ◽  
Binding Mechanisms ◽  
Ricin A

Abstract A deadly pandemic named COVID-19 caused by a new coronavirus SARS- CoV-2 has 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 results of a novel broad range anti-infective fusion protein RTAM-PAP1 against the various key pro- teins 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, pokeweed antiviral protein from leaves and the lectin griffithsin using CoDockPP special COVID-19 version. These experiments revealed novel binding mechanisms of RTAM-PAP1 with high affinity to numerous targets with anti-SARS-CoV-2 effects. RTAM-PAP1 was further characterized in a preliminary toxicity study in mice and was found to likely be a potent anti- SARS-CoV-2 agent. These findings might lead to the discovery of novel SARS-CoV-2 targets and therapeutic protein structures.

The Effect of a Monoclonal Antibody Coupled to Ricin A Chain-Derived Peptides on Endothelial Cells in Vitro: Insights into Toxin-Mediated Vascular Damage

2000 ◽  
Vol 258 (2) ◽  
pp. 417-424 ◽  
Author(s):  
Roxana Baluna ◽  
Elaine Coleman ◽  
Chandria Jones ◽  
Victor Ghetie ◽  
Ellen S. Vitetta
Keyword(s):  
Monoclonal Antibody ◽  
Endothelial Cells ◽  
Vascular Damage ◽  
Ricin A Chain ◽  
A Chain ◽  
Ricin A

HIV-infected cells are killed by rCD4-ricin A chain

Science ◽  
1988 ◽  
Vol 242 (4882) ◽  
pp. 1166-1168 ◽  
Author(s):  
M. Till ◽  
V Ghetie ◽  
T Gregory ◽  
E. Patzer ◽  
J. Porter ◽  
...  
Keyword(s):  
Ricin A Chain ◽  
Infected Cells ◽  
A Chain ◽  
Ricin A

Cyclosporin A and cyclosporin SDZ PSC 833 enhance anti-CD5 ricin A- chain immunotoxins in human leukemic T cells

Blood ◽  
1994 ◽  
Vol 83 (2) ◽  
pp. 482-489 ◽  
Author(s):  
JP Jaffrezou ◽  
BI Sikic ◽  
G Laurent
Keyword(s):  
Cyclosporin A ◽  
Small Population ◽  
High Dose ◽  
Ricin A Chain ◽  
Psc 833 ◽  
A Chain ◽  
Ricin A ◽  
Sdz Psc 833

Abstract Recent studies have shown that cyclosporin A (CsA) may affect ricin A- chain immunotoxin (RTA-IT) therapy. In this study, we evaluated the ability of CsA and its nonimmunosuppressive analog, SDZ PSC 833, to enhance anti-CD5 T101 RTA-ITs in vitro. Both 4 mumol/L CsA and 4 mumol/L SDZ PSC 833 significantly and specifically enhanced the cytotoxic activity of T101 RTA-IT on the human lymphoblastic T-cell line, CEM III (101-fold and 105-fold, respectively). Furthermore, these Cs also enhanced the cytotoxicity of the more potent T101 F(ab')2 RTA- IT (ninefold and eightfold, respectively). The effect of human plasma, originating from four patients enrolled in a phase I high-dose CsA regimen, was examined on T101 RTA-IT cytotoxicity on CEM III cells. In each case, with plasma CsA levels between 3,090 and 4,860 ng/mL (2.5 to 4 mumol/L), a significant increase in T101 RTA-IT-mediated cytotoxicity was observed ranging from 31% to 60%. Neither CsA nor SDZ PSC 833 affected the rate of RTA-IT binding, internalization, intracellular trafficking, or degradation. Analysis of internalized T101 RTA-IT molecules showed that these were essentially intact, which suggests that these enhancers may act only on a small population of RTA-ITs that escapes present investigational techniques. In conclusion, because the concentrations used are clinically achievable, Cs appear to be promising agents for in vivo enhancement of RTA-ITs.

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