Molnupiravir, a wide-spectrum antiviral that is currently in phase 2/3 clinical trials for the treatment of COVID-19, is proposed to inhibit viral replication by a mechanism known as ‘lethal mutagenesis’. Two recently published studies reveal the biochemical and structural bases of how molnupiravir disrupts the fidelity of SARS-CoV-2 genome replication and prevents viral propagation by fostering error accumulation in a process referred to as ‘error catastrophe’.
Pfizer Inc (PFE.N) said on Thursday it was recalling all lots of its anti-smoking treatment, Chantix, due to high levels of cancer-causing agents called nitrosamines in the pills.
The drugmaker paused distribution of the drug in June, and has already recalled a number of lots of the medicine so far. [USN: L4N2PK3WK]
Pfizer asked wholesalers and distributors on Thursday to stop the use and distribution of the tablets immediately.
Pfizer Inc said on Thursday it was recalling all lots of its anti-smoking treatment, Chantix, due to high levels of cancer-causing agents called nitrosamines in the pills.
Only two new coronaviruses have spread globally the past 2 decades: SARS-CoV, which caused an outbreak of severe acute respiratory syndrome (SARS) in 2,003 and SARS-CoV-2, the virus that causes COVID-19. But that may just be the tip of the iceberg of undetected infections with related viruses emerging from bats, a new paper claims. In a preprint published yesterday researchers estimate that an average of 400,000 people are likely infected with SARS-related coronaviruses every year, in spillovers that never grow into detectable outbreaks.
The researchers, including Peter Daszak from the EcoHealth Alliance and Linfa Wang from Duke-NUS Medical School in Singapore, created a detailed map of the habitats of 23 bat species known to harbor SARS-related coronaviruses, the group to which SARS-CoV and SARS-CoV-2 belong, and then overlaid it with data on where humans live to create a map of potential infection hot spots. They found that close to 500 million people live in areas where spillovers can occur, including northern India, Nepal, Myanmar, and most of Southeast Asia. The risk is highest in southern China, Vietnam, Cambodia, and on Java and other islands in Indonesia (see map, below).
Study pinpoints Asian regions that could spark the next coronavirus pandemic.
A new Rutgers study will examine how COVID-19 is affecting individuals in a number of cognitive-related areas, including memory loss, “brain fog,” and dementia.
“Many people who recover from mild or moderate COVID-19 notice slowed thinking or memory loss, and this motivated us to leverage our experience in studying cognitive issues related to Alzheimer’s disease, multiple sclerosis, and HIV to examine this phenomenon,” said Dr. William T. Hu, associate professor and chief of cognitive neurology at Rutgers Robert Wood Johnson Medical School and the Institute for Health, Health Care Policy, and Aging Research.
A leading cognitive neurologist and neuroscientist, Dr. Hu is spearheading the characterization of cognitive impairment following mild-to-moderate COVID-19 at Rutgers.
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern threatens the efficacy of existing vaccines and therapeutic antibodies and underscores the need for additional antibody-based tools that potently neutralize variants by targeting multiple sites of the spike protein. We isolated 216 monoclonal antibodies targeting SARS-CoV-2 from plasmablasts and memory B cells collected from patients with coronavirus disease 2019. The three most potent antibodies targeted distinct regions of the receptor-binding domain (RBD), and all three neutralized the SARS-CoV-2 Alpha and Beta variants. The crystal structure of the most potent antibody, CV503, revealed that it binds to the ridge region of SARS-CoV-2 RBD, competes with the angiotensin converting enzyme 2 receptor, and has limited contact with key variant residues K417, E484 and N501. We designed bispecific antibodies by combining non-overlapping specificities and identified five bispecific antibodies that inhibit SARS-CoV-2 infection at concentrations of less than 1 ng/mL. Through a distinct mode of action, three bispecific antibodies cross-linked adjacent spike proteins using dual N-terminal domain-RBD specificities. One bispecific antibody was greater than 100-fold more potent than a cocktail of its parent monoclonals in vitro and prevented clinical disease in a hamster model at a 2.5 mg/kg dose. Notably, two bispecific antibodies in our panel comparably neutralized the Alpha, Beta, Gamma and Delta variants and wild-type virus. Furthermore, a bispecific antibody that neutralized the Beta variant protected hamsters against SARS-CoV-2 expressing the E484K mutation. Thus, bispecific antibodies represent a promising next-generation countermeasure against SARS-CoV-2 variants of concern.
Bispecific antibodies targeting multiple regions of the SARS-CoV-2 spike protein comparably neutralize variants of concern and wild-type virus.
The first-in-human clinical trial for a candidate treatment for individuals living with human immunodeficiency virus type 1 is starting soon after its maker, Excision BioTherapeutics, today received an Investigational New Drug clearance from the U.S. Food and Drug Administration (FDA).
The FDA’s IND approval sets the stage for the very first Phase I/II trial to evaluate EBT-101 as a functional cure for chronic HIV based on the endpoints of safety, tolerability, and efficacy.
EBT-101, an in vivo, CRISPR-based drug that targets HIV proviral DNA, is a unique gene therapy that leverages CRISPR’s viral defense capability against bacteria. It uses an adeno-associated virus (AAV) to deliver a one-time treatment to functionally cure HIV infections. Preclinical studies show that it can excise HIV proviral DNA in multiple cell lines, including both human primary cells and multiple animal models and non-human primates.
The short curing time and consequently quick healing process is advantageous for these self-healing structures with embedded healing agent reservoirs compared to many other previously reported self-healing materials. For instance, self-healing materials with microvascular networks reported by Toohey et al.18 needed to be kept at room temperature for a period of 12 hours in order to become healed. Self-healing materials with interpenetrating microvascular networks reported by Hansen et al.32 had to go under cyclic bending (50 cycles at 100 μ m displacement) to enhance the mixing of the healing agents at the location of the crack, and after that required to be subjected to 48 hours of curing at 30 °C.
Various mechanical tests were conducted to investigate the healing capability of the structures. For each test, three identical samples with an overall dimension of 5 × 10 × 77 mm (H × W × L) were printed using a top-down SLA-based 3D printer. A notch with equal width and depth of 200 µm was incorporated in the middle of the CAD (computer aided design) model of two out of three specimens (Fig. 1a). This notch enhances the repeatability of the experiments and encourages the initiation of a straight crack under flexural (3-point bending) tests32. When a crack forms, propagates, and reaches the reservoir, the resin wicks into the crack planes as a result of capillary forces and closes the crack when it becomes cured under exposure to UV light. These forces are not high enough to drain out and deplete the large amount of healing agent in the reservoirs. The agent’s relatively high viscosity, approximately 850‑1000 cps at 25 °C, further aids in limiting its flow out of the damaged area. After healing, the specimen is tested again, and a new crack is formed under a new critical load and the aforementioned process is repeated. The small amount of leaked healing agent in the self-healing samples becomes cured relatively quickly under the UV radiation with a wavelength of 405 nm. A UV-light source was employed to cure the leaked-healing agent for 3 min. at 50 °C. To compare the effectiveness of the capillary forces for filling the crack, the notch of the second sample was manually filled before the tests. The last unnotched specimen (virgin) remained unfilled and was tested to provide a reference. It is worth noting that for simplicity’s sake, the structures were placed into a UV oven for curing; however, other types of UV sources can initiate and complete the healing process. In the case of a difficult to access part, on-site repair can be easily implemented using a remote UV source. Additionally, unloading the structure is not necessary to the healing process. A damaged structure is able to cure under loading as the healing mechanism is not affected.
The samples underwent tensile tests following the ASTM D638 standard and their force-displacement curves were recorded at a constant crosshead speed of 13 mm min−1. Figure 2 shows the force-displacement curves for each specimen type. There was a difference of 22% between the tensile fracture load of the virgin specimen without a notch and the sample that was manually repaired. By comparing the fracture force of the healed sample before and after healing (182 N for Capillary – Cycle 1 and 199 N for Capillary – Cycle 2), it can be seen that the fracture force increases by around 17 N after the sample was repaired. There is a significant difference between the fracture force of the manually repaired sample and the sample after healing (Capillary – Cycle 2). This indicates that the self-healing process is effective and is reviving the original mechanical performance of the structure.
“We then go on to show that dopamine is not a reward molecule at all. It instead helps encode information about all types of important and relevant events and drive adaptive behavior—regardless of whether it is positive or negative.”
Summary: A new study finds dopamine increases responses to stressful stimuli, not just pleasurable ones. The findings could have implications for the treatment of mental health disorders and addiction.
Source: Vanderbilt University
Pioneering research shows that dopamine levels increase in response to stressful stimuli, and not just pleasurable ones, potentially rewriting facts about the “feel-good” hormone—a critical mediator of many psychiatric diseases. This discovery is cause to rethink treatment for psychiatric disease and addiction.
This research was led by Erin Calipari, assistant professor of pharmacology, and Munir Gunes Kutlu, a postdoctoral fellow in Calipari’s laboratory.
Kathy Patten, a grandmother from Baltimore, suffered a heart attack and spent 45 long minutes clinically dead. But some intense CPR actually managed to bring her back to life, giving her a second chance that local news stations are calling a “medical miracle.”
Patten has reportedly made an almost full recovery, something that is exceedingly rare. While TV dramas give the impression that CPR is often successful, the reality is grim. Only around 10.6 percent of those who experience cardiac arrest are later discharged from the hospital, according to a 2018 study, though those numbers fluctuate depending the severity and timing of the incident.
“I’m so grateful God gave me a second chance,” Patten told CBS affiliate WJZ-TV. “I’m just going to be the best person I can be. It’s very scary, coming back is a second chance of life.”
That fossil wasn’t enough to confirm Africa as our homeland. Since that discovery, paleoanthropologists have amassed many thousands of fossils, and the evidence over and over again has pointed to Africa as our place of origin. Genetic studies reinforce that story. African apes are indeed our closest living relatives, with chimpanzees more closely related to us than to gorillas. In fact, many scientists now include great apes in the hominid family, using the narrower term “hominin” to refer to humans and our extinct cousins.
In a field with a reputation for bitter feuds and rivalries, the notion of humankind’s African origins unifies human evolution researchers. “I think everybody agrees and understands that Africa was very pivotal in the evolution of our species,” says Charles Musiba, a paleoanthropologist at the University of Colorado Denver.
Paleoanthropologists have sketched a rough timeline of how that evolution played out. Sometime between 9 million and 6 million years ago, the first hominins evolved. Walking upright on two legs distinguished our ancestors from other apes; our ancestors also had smaller canine teeth, perhaps a sign of less aggression and a change in social interactions. Between about 3.5 million and 3 million years ago, humankind’s forerunners ventured beyond wooded areas. Africa was growing drier, and grasslands spread across the continent. Hominins were also crafting stone tools by this time. The human genus, Homo, arrived between 2.5 million and 2 million years ago, maybe earlier, with larger brains than their predecessors. By at least 2 million years ago, Homo members started traveling from Africa to Eurasia. By about 300,000 years ago, Homo sapiens, our species, emerged.