Vipin M. Vashishtha Profile picture
Apr 5, 2024 9 tweets 3 min read Read on X
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/ Image
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/ Image
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/ Image
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/ Image
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/ Image
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/ Image
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/ Image
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

science.org/doi/10.1126/sc…

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More from @vipintukur

Apr 25
Could this molecule be 'checkmate' for SARS-CoV-2?

A research team has developed new drug candidates major protease blockers, AVI-4516 & AVI-4773 that show great promise against SARS-CoV-2 & potentially other coronaviruses that could cause future pandemics 1/ Image
In preclinical testing, the compounds performed better than Paxlovid against SARS-CoV-2 and the Middle East Respiratory Syndrome (MERS) virus, which periodically causes deadly outbreaks around the world. 2/ Image
These MPro blocking compounds could inhibit coronaviruses in general, giving us a head start against the next pandemic. We need to get them across the finish line and into clinical trials. 3/ Image
Read 13 tweets
Apr 21
Remember COVID toes?

➡️ A study has found that people with pandemic chilblains have an unusually strong immune response to SARS-CoV-2, driven by overactive plasmacytoid dendritic cells (pDCs) responding to TLR7 signals. 1/ Image
Given the essential role of type I interferon in protective immunity against SARS2 & the association of chilblains with inherited type I interferonopathies, researchers hypothesized that excessive I-IFN responses to SARS2 might underlie the occurrence of chilblains 2/ Image
They identified a transient I-IFN signature in chilblain lesions, accompanied by an acral infiltration of activated plasmacytoid dendritic cells (pDCs). Patients with chilblains were otherwise asymptomatic or had mild disease without seroconversion. 3/ Image
Read 6 tweets
Apr 19
Differential DNA methylation 7 months after SARS-CoV-2 infection

A NEW study detected associations between changes in DNA methylation in individuals who had even asymptomatic or mild SARS-CoV-2 infections as compared to their household controls after 7 moths of infection 1/ Image
Aberrant DNA methylation patterns have been linked to various diseases, including cancer and metabolic disorders. 

These changes resembled patterns seen in autoimmune or inflammatory diseases, suggesting long-term epigenetic remodeling even in mild cases. 2/ Image
This study shows that even mild or symptom-free COVID-19 infections can cause lasting changes in how certain genes are turned on or off in the body, seven months after infection. 3/ Image
Read 7 tweets
Apr 19
New research reveals that calming the brain's immune cells may reduce Alzheimer's disease inflammation. The study highlights the importance of norepinephrine, which could lead to more targeted, early, and personalized treatments. 1/ Image
Norepinephrine is a major signaling factor in the brain and affects almost every cell type. In the context of neurodegenerative diseases such as Alzheimer's disease, it has been shown to be anti-inflammatory. 2/ Image
In this study, the researchers describe how enhancing norepinephrine's action on microglia can mitigate early inflammatory changes and neuronal injury in Alzheimer's models. 3/ Image
Read 11 tweets
Apr 17
#Metformin- A wonder drug!

➡️ A NEW study finds Metformin could prevent a form of acute myeloid leukemia (AML) in people at high risk of the disease.
Researchers investigated how metformin could prevent abnormal blood stem cells w/ genetic changes from progressing to AML 1/ Image
Metformin impacts mitochondrial metabolism, & these pre-cancerous cells need this energy to keep growing. By blocking this process, researchers stop the cells from expanding & progressing towards AML, whilst also reversing other effects of mutated DNMT3A gene 2/ Image
Thanks to recent advances, individuals at high risk of AML can be identified years in advance using blood tests and blood DNA analysis, but there's no suitable treatment that can prevent them from developing the disease. 3/ Image
Read 10 tweets
Apr 16
Does SARS-CoV-2 Possess “Allergen-Like” Epitopes?

It has been reported that repeated administration of some COVID vaccines induces high IgG4 levels.

New research revealed a surprising IgE anti-RBD response after both natural infection & several SARS-CoV-2 vaccines. 1/ Image
Presence of IgG4 & IgE in COVID-19 suggests that the virus may induce an “allergic-like” response to evade immune surveillance, leading to a shift from Th1 to Th2 cells, which promotes tolerance to the virus & potentially contributes to chronic infection & may be LongCovid 2/ Image
An increase in IgG4 levels is typically associated w/ immunological tolerance & develops after prolonged exposure to antigens. While tolerance to an allergen benefits the host in Allergen Immunotherapy, in viral infection, it enables viral persistence rather than clearance 3/ Image
Read 12 tweets

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