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Archive - Jul 7, 2020

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Under Oxidative Stress from Hydrogen Peroxide (H2O2), Defensive Clp Proteins of E. coli Ensure That Iron Pools Remain Sufficient for Reactivation of Key Oxidized Metalloenzymes

Researchers at the University of Illinois, Urbana-Champaign, have shown that, during oxidative stress from hydrogen peroxide (H2O2), Clp proteins in E. coli act to ensure that cellular pools of iron remain adequate and accessible for the reactivation of oxidized metalloenzymes. This system countervails the simultaneous drive to sequester iron, which can react with H2O2 and cause DNA damage. The researchers concluded that E. coli cells are able to strike a careful balance, diminishing iron pools enough to protect the cell’s DNA (from hydroxyl radicals that are produced when iron reacts with H2O2), but keeping the iron pools substantial enough so that critical iron-dependent enzymes can be repaired. The results were published online on June 29, 2020 in the Journal of Bacteriology. The article is titled “During Oxidative Stress the Clp Proteins of Escherichia coli Ensure That Iron Pools Remain Sufficient to Reactivate Oxidized Metalloenzymes.” The authors are first author Ananya Sen (photo), Yidan Zhou, and Professor James A. Imlay, from the Department of Microbiology at the University of Illinois, Urbana-Champaign. The authors noted that “H2O2 is formed in natural environments by both biotic and abiotic processes. It easily enters the cytoplasms of microorganisms, where it can disrupt growth by inactivating iron-dependent enzymes. It also reacts with the intracellular iron pool, generating hydroxyl radicals that can lethally damage DNA.” Consequently, the authors said that bacteria have developed various mechanisms to combat the potential damage that can be caused by H2O2. Bacteria possess H2O2-responsive transcription factors that control defensive regulons (sets of related genes that are activated together). These defensive regulons typically code for catalases and peroxidases that scavenge H2O2.

CytoDyn’s Leronlimab Prevents Transmission of SHIV in Macaque Study; Results of Preclinical Study Presented Tuesday, July 7, in Oral Presentation at the 23rd International AIDS Conference (AIDS 2020)

On July 7, CytoDyn Inc. (OTC.QB: CYDY), a late-stage biotechnology company developing leronlimab (PRO 140), a CCR5 antagonist with potential clinical indications for HIV, COVID-19, cancer, GvHD (graft versus host disease), and NASH (non-alcoholic steato-hepatitis), announced the results from a preclinical macaque study evaluating leronlimab as pre-exposure prophylaxis (PrEP) to prevent sexual HIV transmission. The study evaluated the impact of a macaque-equivalent dose of either 350 mg (once weekly) or 700 mg (bi-monthly) leronlimab on acquisition of infection in a total of 18 animals, and found that the equivalent 700 mg bi-monthly leronlimab dose completely prevented rectal transmission of Simian-Human Immunodeficiency Virus (SHIV) in macaques. These results were presented today in an oral presentation titled “CCR5 Antibody Blockade Protects Rhesus Macaques from Rectal SHIV Acquisition" at the 23rd International AIDS Conference (AIDS 2020) (https://www.aids2020.org/). “The results reported here in the preclinical macaque model of HIV sexual transmission support leronlimab as a possible PrEP (pre-exposure prophylaxis) agent at a time when long-acting human HIV PrEP options are limited,” said Jonah Sacha, PhD, Professor at Oregon Health & Science University (OHSU), and the study’s lead investigator. “We are eager to build upon these preclinical results describing leronlimab’s utility in HIV prevention by initiating clinical studies for leronlimab as a PrEP treatment. Current PrEP options require a continued daily dosing regimen in order to be effective and are inherently difficult to maintain in the long-term,” said Nader Pourhassan, PhD, President and Chief Executive Officer of CytoDyn, which has developed leronlimab.

Novavax Announces $1.6 Billion Funding from Operation Warp Speed to Support Late-Stage Clinical Development, Pivotal Phase 3 Clinical Trial to Support Licensure, Large-Scale Manufacturing & Production of 100 Million Vaccine Doses Starting in Late 2020

On June 7, 2020, Novavax, Inc. (Nasdaq: NVAX) (https://novavax.com/), a late-stage biotechnology company developing next-generation vaccines for serious infectious diseases, announced that it has been selected to participate in Operation Warp Speed (OWS), a U.S. government program that aims to begin delivering millions of doses of a safe, effective vaccine for COVID-19 in 2021. Novavax has been awarded $1.6 billion by the federal government to complete late-stage clinical development, including a pivotal Phase 3 clinical trial; establish large-scale manufacturing; and deliver 100 million doses of NVX CoV2373, Novavax’ COVID-19 vaccine candidate, as early as late 2020. NVX CoV2373 consists of a stable, prefusion protein made using its proprietary nanoparticle technology and includes Novavax’ proprietary Matrix M™ adjuvant. “The pandemic has caused an unprecedented public health crisis, making it more important than ever that industry, government, and funding entities join forces to defeat the novel coronavirus together. We are honored to partner with Operation Warp Speed to move our vaccine candidate forward with extraordinary urgency in the quest to provide vital protection to our nation’s population,” said Stanley C. Erck, MBA, President and Chief Executive Officer of Novavax. “We are grateful to the U.S. government for its confidence in our technology platform, and are working tirelessly to develop and produce a vaccine for this global health crisis.” Under terms of the agreement, Novavax will demonstrate it can rapidly stand up large-scale manufacturing and transition into ongoing production, including the capability to stockpile and distribute large quantities of NVX-CoV2373 when needed.