How SARS-CoV-2 replicates once it enters the cells, has made surprising discoveries that could be the foundation for future antiviral therapies. It also has important implications as replication of the SARS-CoV-2 has, so far, received less attention from researchers. 1/
The viral life cycle can be broken down into 2 main stages: the 1st where the virus enters the cell, & 2nd is replication where the virus uses the molecular machinery of the cell to replicate itself by building its parts, assembling them into new viruses that can then exit 2/
The new study focuses on how the Envelope protein of SARS-CoV-2 controls late stages of viral replication. Coronaviral Envelope (E) proteins are pentameric viroporins that play essential roles in assembly, release, and pathogenesis. 3/
The researchers marked the Envelope protein with fluorescent tags to track its movement within cells and used proteomics to identify key pathways that allow SARS-CoV-2 to take over the internal compartments of the infected cell—known as organelles—for its replication. 4/
They identified a surprising aspect of its replication in its use of a compartment called the lysosome during viral release. The Envelope protein localises itself to the Golgi complex and to lysosomes. 5/
Lysosomes are acidic, degradative organelles, but SARS-CoV-2 uses its Envelope protein as an ion-channel to neutralize their acidity and so enhance viral release. 6/
So the data outline trafficking pathways and routes taken by the E viroporin of SARS-CoV-2, linking viral sequences with cellular factors that govern movement between the ER, Golgi, and lysosomes. 7/
Such insights on replication could eventually be applied to create new antivirals that inhibit the channel activity of the Envelope protein. These could apply not only to SARS-CoV-2, but to the β-coronavirus family and any other virus that replicates with the same mechanisms. 8/
These findings show what an exquisite cell biologist the SARS-CoV-2 virus is, and shed new light onto how infection with SARS-CoV-2 can disrupt the function of essential intracellular compartments, known as organelles 9/9
A meta-analysis from Egypt of 125 studies involving over 4 million COVID survivors shows that months to years after infection, fatigue was the most common symptom at 43%. Around 27% of people experience cognitive impairment after COVID infection. 1/
Further, 28% experienced memory issues, 24% sleep disorders, 20% headaches, 16% dizziness, 14% depression, and 13% anxiety, with significant variability depending on follow‑up time, disease severity, sex, and BMI. 2/
Neurological symptoms are common & persistent in COVID survivors. This study highlights significant burden these symptoms place on individuals, emphasizing the need for well-resourced multidisciplinary healthcare services to support post-COVID recovery. 3/3
A new review on neuroimmune pathophysiology of #LongCOVID explores how SARS-CoV-2 can cause lasting neurological symptoms through a combination of direct infection, immune dysregulation, and persistent inflammation. 1/
Key mechanisms include viral antigen persistence, autoimmunity, blood–brain barrier disruption, neurotransmitter imbalances, and glial cell dysfunction. The authors link these processes to cognitive impairment, fatigue, dysautonomia, and other Long COVID symptoms. 2/
Despite the perception that COVID-19 is now a mild disease, there is overwhelming evidence indicating that SARS-CoV-2 infection is capable of producing widespread post-acute sequelae in a significant percentage of infections. 3/
As people get older, a growing population of cells starts to consume more energy — perhaps because the cells accumulate damage that leads them to rev up processes such as inflammation. 1/
An emerging hypothesis suggests that the brain accommodates these energy-hogging ‘senescent cells’ by stripping resources from other biological processes, which ultimately results in outward signs of ageing, such as greying hair or a reduction in muscle mass. 2/
It’s one example of a growing understanding of how our brains control ageing and how psychological stress can accelerate the process at a molecular level. 3/
A NEW study found that the SARS-CoV-2 nonstructural protein 15 (nsp15) helps the virus hide from the immune system in human lung and nasal cells. The nsp15 endoribonuclease is important in promoting virus replication and influencing disease severity. 1/
SARS2 variants lacking this activity exhibit impaired replication & cause milder disease, highlighting nsp15 as a key virulence factor. This underscores the importance of nsp15’s endoribonuclease activity in both promoting virus replication & influencing disease severity. 2/
The viral variants lacking nsp15 endoribonuclease activity elicited higher innate immune responses and exhibited reduced replication in human stem cell–derived lung alveolar type II epithelial cells, as well as in the lungs of infected hamsters. 3/
Researchers developed a 23-amino acid peptide that mimics ACE2 and effectively binds the SARS-CoV-2 spike protein, preventing viral entry. 1/
The peptide demonstrated potent antiviral activity against both the original and Omicron strains, with a therapeutic index greater than 20, indicating strong potential for therapeutic use. 2/
Moreover, future viruses from this family of coronaviruses may likely use ACE2 as their host cell receptor, as recently demonstrated in the MERS Virus of bats and, therefore, the ACE2 decoy therapeutic may have future applications as well. 3/
A NEW preprint found that submaximal exercise in people with #LongCOVID caused large microclots to fragment into smaller microclots and this then triggered increases in inflammatory and vascular injury markers. 1/
The breakdown of large microclots, rather than clearing them from circulation, was linked to reduced oxygen uptake and heightened inflammation. 2/
The data suggest that while the immune system tries to control inflammation caused by microclot fragmentation after physical exertion, its compensatory mechanisms are inadequate or failing. 3/