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 2
Even after 5 yrs since its arrival, SARS-CoV-2 mutations keep emerging. A new variant LP.8.1 is rising. Almost 1 in 5 COVID cases in New South Wales are it. In the UK, it accounts for at least 3 in 5 cases. Just what is LP.8.1? Is it worrying? 1/ Image
LP.8.1 was first detected in July 2024. It’s a descendant of Omicron, specifically of KP.1.1.3, which is descended from JN.1, a subvariant that caused large waves of COVID infections around the world in late 2023 and early 2024. 2/ Image
The WHO designated LP.8.1 as a variant under monitoring in January. This was in response to its significant growth globally, and reflects that it has genetic changes which may allow the virus to spread more easily and pose a greater risk to human health. 3/ Image
Read 8 tweets
Apr 1
SARS-CoV-2 spike protein binds fibrinogen, causing thrombo-inflammation, according to a recent study. The virus must bind to fibrinogen, but why? Could this relationship help the virus evolve? Could this cause post-COVID heart attacks? 1/ Image
Scientists often think they grasp a virus's anatomy, tricks, and body movement. But occasionally, we discover something unexpected that radically transforms how we view an infection. 2/ Image
Some strategies are well documented: antigenic drift, glycan shielding, immune suppression. But every so often, we stumble upon a novel mechanism that redefines our understanding of viral pathogenesis. 3/ Image
Read 17 tweets
Mar 27
COVID-19 increases the risk of autoimmune diseases including rheumatoid arthritis and type 1 diabetes. The virus alters the immune system in unknown ways, making it difficult to design medicines to prevent post-COVID autoimmunity. 1/ Image
One leading hypothesis involves viral “molecular mimics”—proteins from the virus that resemble the body’s own proteins. These mimics may trigger an immune response against the virus but unintentionally cause the immune system to target healthy tissues as well. 2/ Image
Thanks to recent advancements in data analysis and machine learning, scientists have now identified a set of SARS-CoV-2-derived molecular mimics that may play a role in initiating autoimmune responses. 3/ Image
Read 10 tweets
Mar 27
mRNA-COVID-19 vaccines train the 'long-term memory' of immune system

Researchers have determined that the novel mRNA-COVID-19 vaccines not only induce acquired immune responses such as antibody production, but also cause persistent epigenetic changes in innate immune cells 1/ Image
Thus, vaccination with mRNA vaccines could lead to an enhanced immune response to future encounters with pathogens which are not specifically targeted by the vaccine. 2/ Image
These findings reveal that mRNA vaccines cause epigenetic 'training' of innate immune cells, sustaining immunological response. Epigenetic alterations may enable long-lasting innate immunity that enhances acquired immune system protection. 3/ Image
Read 12 tweets
Mar 26
In a proof-of-concept study, people with cognitive impairment in #LongCOVID were found to have asymmetrical glymphatic dysfunction in the left hemisphere of the brain which also correlated with disruption of the blood-brain barrier (BBB). 1/ Image
A group of researchers used special MRI techniques to assess perivascular spaces in the brain of 14 individuals with LongCOVID compared to 10 healthy controls. 2/ Image
A significant reduction in the DTI-ALPS index—a measure of glymphatic function—in the left hemisphere of LongCOVID patients was found, indicating impaired waste clearance in the brain. 3/ Image
Read 6 tweets
Mar 25
Sugar coatings aren't only for candies; they also help viruses, like the ones that cause COVID-19, hide from their hosts' immune system.

Now, researchers have developed a universal vaccine that targets coronaviruses and the sugars that they use as cover. 1/ Image
As demonstrated in animal studies, the vaccine removed sugar molecules from an area of a coronavirus spike protein that rarely mutates and created effective and plentiful antibodies to inactivate the virus. 2/ Image
Researchers say that the premise of this research is simple: it's an effective vaccine that targets more than one coronavirus at a time, which will allow individuals to receive a single shot for protection against multiple infectious agents. 3/ Image
Read 10 tweets

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