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SARS-CoV-2 Virus Circulated Undetected Months Before First COVID-19 Cases in Wuhan, China, Scientists Conclude; Simulations Suggest Most Zoonotic Viruses Die Out Before Causing Pandemic

Using molecular dating tools and epidemiological simulations, researchers at the University of California (UC) San Diego School of Medicine, with colleagues at the University of Arizona and Illumina, Inc., estimate that the SARS-CoV-2 virus was likely circulating undetected for at most two months before the first human cases of COVID-19 were described in Wuhan, China in late-December 2019. In an article published online on March 18, 2021 in Science, the scientists also note that their simulations suggest that the mutating virus dies out naturally more than three-quarters of the time without causing an epidemic. The open-access article is titled “Timing the SARS-CoV-2 Index Case in Hubei Province.” ( "Our study was designed to answer the question of how long could SARS-CoV-2 have circulated in China before it was discovered," said senior author Joel O. Wertheim, PhD, Associate Professor in the Division of Infectious Diseases and Global Public Health at UC San Diego School of Medicine. "To answer this question, we combined three important pieces of information: a detailed understanding of SARS-CoV-2 spread in Wuhan before the lockdown, the genetic diversity of the virus in China, and reports of the earliest cases of COVID-19 in China. By combining these disparate lines of evidence, we were able to put an upper limit of mid-October 2019 for when SARS-CoV-2 started circulating in Hubei province." Cases of COVID-19 were first reported in late-December 2019 in Wuhan, located in the Hubei province of central China. The virus quickly spread beyond Hubei. Chinese authorities cordoned off the region and implemented mitigation measures nationwide.

Immune Receptor Protein (TARM1) Could Hold Key to Treatment of Autoimmune Diseases Such As Rheumatoid Arthritis

TARM1 (T cell-interacting, activating receptor on myeloid cells-1) is a immune receptor protein whose role in the functioning of the immune system is largely unknown. In a new study, scientists from Japan have explored the potential role of TARM1 in the pathogenesis of rheumatoid arthritis by analyzing mouse models. They found that TARM1 activated dendritic cells, and development of collagen-induced arthritis (CIA) was notably suppressed in TARM1-deficient mice and by treatment with TARM1-inhibitory soluble TARM1 proteins. This makes the protein a potential therapeutic target. Autoimmune diseases are typically caused when the immune system, whose purpose is to deal with foreign threats to the body, incorrectly recognizes the body’s own proteins and cells as threats and activates immune cells to attack them. In the case of rheumatoid arthritis, a well-known autoimmune disease, immune cells erroneously attack the body’s own joint components and proteins, causing painful inflammation and even the destruction of bone. Scientists from Japan have now taken a major step toward understanding and, potentially, treating rheumatoid arthritis better, with their discovery in a new study. The development of autoimmune diseases is an incredibly complex process, involving several key players including genetic and environmental factors. Dendritic cells (DCs), which are responsible for kick-starting the immune response against infections, are one of the main immune cells involved in the pathogenesis of autoimmune diseases. All immune cells, including DCs, are equipped with a variety of receptors on their surfaces, which can either amplify or suppress the immune response. One such receptor is the TARM1 protein.

Ultrasound Has Potential to Damage Coronaviruses, MIT Simulations Suggest

The coronavirus' structure is an all-too-familiar image, with its densely packed surface receptors resembling a thorny crown. These spike-like proteins latch onto healthy cells and trigger the invasion of viral RNA. While the virus' geometry and infection strategy is generally understood, little is known about its physical integrity. A new study by researchers in MIT's Department of Mechanical Engineering suggests that coronaviruses may be vulnerable to ultrasound vibrations, within the frequencies used in medical diagnostic imaging. Through computer simulations, the team has modeled the virus' mechanical response to vibrations across a range of ultrasound frequencies. They found that vibrations between 25 and 100 megahertz triggered the virus' shell and spikes to collapse and start to rupture within a fraction of a millisecond. This effect was seen in simulations of the virus in air and in water. The results are preliminary, and based on limited data regarding the virus' physical properties. Nevertheless, the researchers say their findings are a first hint at a possible ultrasound-based treatment for coronaviruses, including the novel SARS-CoV-2 virus. How exactly ultrasound could be administered, and how effective it would be in damaging the virus within the complexity of the human body, are among the major questions scientists will have to tackle going forward. "We've proven that under ultrasound excitation the coronavirus shell and spikes will vibrate, and the amplitude of that vibration will be very large, producing strains that could break certain parts of the virus, doing visible damage to the outer shell and possibly invisible damage to the RNA inside," says Tomasz Wierzbicki, PhD, Professor of Applied Mechanics at MIT. "The hope is that our paper will initiate a discussion across various disciplines."

Kimera Labs Announces New Standard Measurement for Exosome Potency, Characterization

On March 11, 2021, Kimera® Labs (, one of the nation's top manufacturers of placental mesenchymal stem cell (pMSC) -derived exosomes, today announced the establishment of a novel and more relevant method to quantify and characterize exosomes - the Ross Unit (Ru), in an effort to standardize the measurement of nanovesicle technology. Kimera® Labs says it has established the Ru in order to rectify a misleading concept perpetuated by the tissue-banking industry that has correlated particle counts obtained by nano tracking analysis (NTA) to exosome concentration. In a novel approach to the subject, the Ru accounts solely for exosomal RNA cargo and protein concentration as opposed to gross quantification of all species (excipients) present in a solution. This scientifically valid process was developed by Kimera® Labs, Inc., and will be implemented in XoGlo® certificates of analysis in the first quarter of 2021. Kimera believes that the Ross Unit (Ru) describes a more accurate measurement of the purity and potency of exosome preparations and provides a reproducible method of therapeutic product characterization that will ultimately translate to improved patient outcomes. "When we debuted the Kimera® exosome product, XoGlo®, in 2014, we expended a significant amount of time and effort simply trying to communicate the concept of pMSC-derived paracrine effectors consisting of an invisible nanoparticle suspended in saline," said Duncan Ross PhD, and CEO of Kimera® Labs. "However, it was difficult to correlate the number of vesicles to the potency of a finished product.

Singapore Scientists Develop Novel CRISPR-Cas9-Based Gene Editor to Correct Disease-Causing Mutations; Advance May Open Up Possible Treatment for Up to 40% of Genetic Disorders Caused by Single-Nucleotide Mutations

A team of researchers from the Agency for Science, Technology, and Research's (A*STAR) Genome Institute of Singapore (GIS) has developed a CRISPR-based gene editor, C-to-G Base Editor (CGBE), to correct mutations that cause genetic disorders. Their research was published online on March 2, 2021 in Nature Communications. The open-access article is titled “Programmable C:G to G:C Genome Editing with CRISPR-Cas9-Directed Base Excision Repair Proteins” ( ). One in seventeen people in the world suffers from some type of genetic disorder. Chances are, you or someone you know--a relative, friend, or colleague--is one of approximately 450 million people affected worldwide. Mutations responsible for these disorders can be caused by multiple mutagens--from sunlight to spontaneous errors in your cells. The most common mutation by far is the single-based substitution, in which a single-base in the DNA (such as G) is replaced by another base (such as C). For example, countless cystic fibrosis patients worldwide have C instead of G, leading to defective proteins that cause the genetic disease. In another case, replacing A with T in hemoglobin causes sickle cell anemia. To fix these substitutions, the team invented a CRISPR-based gene editor that precisely changes the defective C within the genome to the desired G. This C-to-G base editor (CGBE) invention opens up treatment options for approximately 40 per cent of the single-base substitutions that are associated with human diseases such as the aforementioned cystic fibrosis, cardiovascular diseases, musculoskeletal diseases, and neurological disorders.

An Old Antibiotic May Combat Drug-Resistant Tuberculosis

For decades, antibiotics have helped hold tuberculosis back, saving untold millions of lives. But their limits are being seriously tested as the bacterium’s tendency to mutate has led to a steady rise in drug-resistant strains. Without new drugs, scientists fear that tuberculosis, deemed largely a controllable disease, may not remain so. In search of new antibiotics, Rockefeller University scientists have landed on an existing compound, naturally produced by a bacterium. Their research, published online on November 16, 2020 in PNAS, elucidates how sorangicin A, first discovered in the 1980s, can destroy even the antibiotic-resistant bacteria that cause tuberculosis. The findings suggest that the compound may be a good candidate for further development as a first-line antibiotic for tuberculosis. The PNAS article is titled “The Antibiotic Sorangicin A Inhibits Promoter DNA Unwinding in a Mycobacterium tuberculosis Rifampicin-Resistant RNA Polymerase.” “Sorangicin inhibits regular strains in very much the same way as rifampin, one of the primary choices for tuberculosis antibiotics. But now we show that, through a different mechanism, it [sorangicin] also traps those variants that escape rifampin,” says Elizabeth Campbell, PhD, a Research Associate Professor at Rockefeller. The antibiotic rifampin works by blocking RNA polymerase (RNAP), an enzyme crucial to bacteria’s survival. This enzyme walks along a strand of DNA, using the genetic information to build an RNA molecule, one nucleotide at a time. Rifampin snaps into the cavity of one of RNAP’s pockets, and physically clogs the path of the RNA molecule when it’s no more than two or three nucleotides long. Without the proper RNA blueprints, the bacterium can’t make new proteins, and dies.

Study Identifies Key Genes in Brain Involved in Encoding Memories

University of Texas Southwestern (UTSW) scientists have identified key genes involved in brain waves that are pivotal for encoding memories. The findings, published online on March 8, 2021 in Nature Neuroscience, could eventually be used to develop novel therapies for people with memory loss disorders such as Alzheimer’s disease and other forms of dementia. The article is titled “Gene-Expression Correlates of the Oscillatory Signatures Supporting Human Episodic Memory Encoding” ( Making a memory involves groups of brain cells firing cooperatively at various frequencies, a phenomenon known as neural oscillations. However, explain study leaders Bradley C. Lega, MD, Associate Professor of Neurological Surgery, Neurology, and Psychiatry, and Genevieve Konopka, PhD, Associate Professor of Neuroscience, the genetic basis of this process is not clear. “There’s a famous saying for 100 years in neuroscience: ‘Neurons that fire together will wire together,’” says Dr. Lega. “We know that cells involved in learning fire in groups and form new connections because of the influence of these oscillations. But how genes regulate this process in people is completely unknown.” Dr. Lega and Dr. Konopka, both members of UTSW’s Peter O’Donnell Jr. Brain Institute, collaborated on a previous study to explore this question, collecting data on neural oscillations from volunteers and using statistical methods to connect this information to data on gene activity collected from postmortem brains. Although these results identified a promising list of genes, Dr. Konopka says, there was a significant shortcoming in the research: The oscillation and genetic data came from different sets of individuals.

Research Reveals 3D Structure Responsible for Multi-Unit Machine Involved in Regulating Gene Expression

For the first time ever, a Northwestern University-led research team has peered inside a human cell to view a multi-subunit machine responsible for regulating gene expression. Called the Mediator-bound pre-initiation complex (Med-PIC), the structure is a key player in determining which genes are activated and which are suppressed. Mediator helps position the rest of the complex--RNA polymerase II and the general transcription factors--at the beginning of genes that the cell wants to transcribe. The researchers visualized the complex in high resolution using cryogenic electron microscopy (cryo-EM), enabling them to better understand how it works. Because this complex plays a role in many diseases, including cancer, neurodegenerative diseases, HIV, and metabolic disorders, researchers' new understanding of its structure could potentially be leveraged to treat disease. "This machine is so basic to every branch of modern molecular biology in the context of gene expression," said Northwestern's Yuan He (at right in photo with colleague), PhD, senior author of the study. "Visualizing the structure in 3D will help us answer basic biological questions, such as how DNA is copied to RNA." "Seeing this structure allows us to understand how it works," added Ryan Abdella, PhD student and the paper's co-first author. "It's like taking apart a common household appliance to see how everything fits together. Now we can understand how the proteins in the complex come together to perform their function." The study was published online on March 11, 2021 in Science. This marks the first time the human Mediator complex has been visualized in 3D in the human cell. The Science article is titled "Structure of the Human Mediator-Bound Transcription Pre-Initiation Complex" (

RNA Editing Protein ADAR1p110 Protects Telomeres and Supports Proliferation In Cancer Cells; Protein May Be Target for Anti-Cancer Therapy

Scientists at The Wistar Institute in Philadelphia have identified a new function of ADAR1, a protein responsible for RNA editing, discovering that the ADAR1p110 isoform regulates genome stability at chromosome ends and is required for continued proliferation of cancer cells. These findings, reported online on March 12, 2021 in Nature Communications, reveal an additional oncogenic function of ADAR1 and reaffirm its potential as a therapeutic target in cancer. The open-access article is titled “ADAR1 RNA Editing Enzyme Regulates R-Loop Formation and Genome Stability at Telomeres in Cancer Cells” ( The lab of Kazuko Nishikura, PhD, Professor in the Gene Expression & Regulation Program of The Wistar Institute Cancer Center, was one of the first to discover ADAR1 in mammalian cells and to characterize the process of RNA editing and its multiple functions in the cell. Similar to changing one or more letters in a written word, RNA editing allows cells to make discrete modifications to single nucleotides within an RNA molecule. This process can affect RNA metabolism and how it is translated into proteins and has implications for neurological and developmental disorders and antitumor immunity. There are two forms of the ADAR1 protein, ADAR1p150 and ADAR1p110. While the RNA editing role of the former, located in the cytoplasm, has been extensively characterized, the function of the nuclear ADAR1p110 isoform has remained elusive. "We discovered that, in the nucleus, ADAR1p110 oversees a similar mechanism to ADAR1p150, the better-known cytoplasmic variant, but the editing process in this case targets particular nucleic acid structures called R-loops when formed at the chromosome ends," said Dr. Nishikura. "Through this function, ADAR1p110 seems to be essential for cancer cell proliferation."

Monoclonal Antibody Combination from Lilly Reduces Risk of Hospitalization & Death by 87% in Phase 3 Trial for Early COVID-19, According to New Data, Company Announces

On March 10,2021, Eli Lilly and Company (NYSE: LLY) announced new data from the randomized, double-blind, placebo-controlled BLAZE-1 Phase 3 study, demonstrating that the monoclonal antibodies bamlanivimab (LY-CoV555) 700 mg and etesevimab (LY-CoV016) 1400 mg together significantly reduced COVID-19 related hospitalizations and deaths ("events") in high-risk patients recently diagnosed with COVID-19. These results provide additional efficacy and safety data that support the use of the dose recently granted both Emergency Use Authorization by the U.S. Food and Drug Administration (FDA) and a positive scientific opinion by the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP). This new Phase 3 cohort of BLAZE-1 included 769 high-risk patients, aged 12 and older with mild to moderate COVID-19 (therapy: n=511; placebo: n=258). There were 4 events in patients taking bamlanivimab with etesevimab and 15 events in patients taking placebo, representing an 87 percent risk reduction (p<0.0001). Bamlanivimab and etesevimab together also demonstrated statistically significant improvements on key secondary endpoints. These results are consistent with those seen in other data sets from BLAZE-1: in the previous Phase 3 cohort, bamlanivimab 2800 mg with etesevimab 2800 mg reduced the risk of hospitalizations and deaths by 70 percent and in the Phase 2 cohort, bamlanivimab alone reduced the risk of hospitalizations and ER visits by approximately 70 percent. The viral load reductions were also consistent with what was observed in the previous Phase 3 cohort of the study.

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