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The toxicity of Clostridium difficile large clostridial toxin B (TcdB) can be reduced by many orders of magnitude by a combination of targeted point mutations. However, a TcdB mutant with five point mutations (referred to herein as mTcdB) still has residual toxicity that can be detected in cell-based assays and in-vivo mouse toxicity assays. This residual toxicity can be effectively removed by treatment...
Pharmacokinetic properties of biotherapeutics are an important aspect of preclinical drug development. The lead identification and optimization space is characterized by aggressive timelines, large sample numbers, a variety of species and matrices, and limited reagent and sample volumes all of which represent challenges for traditional microtiter plate assays. Since the Gyrolab immunoassay platform...
In the current study, we extended our previous works on natural endogenous reverse transcription (NERT) and further examined its potential as a virucide molecular target in sexual transmission of primate lentiviruses. HIV-1 and SIV virions were pretreated with select nucleoside (NRTIs) and nonnucleoside RT inhibitors (NNRTIs), either alone or in combination with NERT-stimulating substances. The effects...
It has been demonstrated that intravirion reverse transcription in human immunodeficiency virus type I (HIV-1) occurs in the presence of physiological substances and that the intravirion HIV-1 reverse transcripts are important for the establishment of infection in nondividing cells. In this report, we demonstrate that the infectivity of the virus produced from replicating peripheral blood lymphocytes...
It has been demonstrated that human immunodeficiency virus type 1 (HIV-1) virions are biochemically active particles, within which reverse transcription can take place even in physiological microenvironments. This process has been termed “natural endogenous reverse transcription” (NERT). In this report, we demonstrate that purified virions of simian immunodeficiency virus (SIV) also contain virus-specific...
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