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…

• • •

Missing some Tweet in this thread? You can try to force a refresh
 

Keep Current with Vipin M. Vashishtha

Vipin M. Vashishtha Profile picture

Stay in touch and get notified when new unrolls are available from this author!

Read all threads

This Thread may be Removed Anytime!

PDF

Twitter may remove this content at anytime! Save it as PDF for later use!

Try unrolling a thread yourself!

how to unroll video
  1. Follow @ThreadReaderApp to mention us!

  2. From a Twitter thread mention us with a keyword "unroll"
@threadreaderapp unroll

Practice here first or read more on our help page!

More from @vipintukur

Jun 26
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/ Image
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/ Image
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
Read 4 tweets
Jun 24
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/ Image
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/ Image
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/ Image
Read 4 tweets
Jun 19
I think, therefore I age!

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/ Image
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/ Image
Read 5 tweets
Jun 17
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/ Image
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/ Image
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/ Image
Read 5 tweets
Jun 16
Researchers developed a 23-amino acid peptide that mimics ACE2 and effectively binds the SARS-CoV-2 spike protein, preventing viral entry. 1/ Image
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/ Image
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/ Image
Read 4 tweets
Jun 5
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/ Image
The breakdown of large microclots, rather than clearing them from circulation, was linked to reduced oxygen uptake and heightened inflammation. 2/ Image
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/ Image
Read 6 tweets

Did Thread Reader help you today?

Support us! We are indie developers!


This site is made by just two indie developers on a laptop doing marketing, support and development! Read more about the story.

Become a Premium Member ($3/month or $30/year) and get exclusive features!

Become Premium

Don't want to be a Premium member but still want to support us?

Make a small donation by buying us coffee ($5) or help with server cost ($10)

Donate via Paypal

Or Donate anonymously using crypto!

Ethereum

0xfe58350B80634f60Fa6Dc149a72b4DFbc17D341E copy

Bitcoin

3ATGMxNzCUFzxpMCHL5sWSt4DVtS8UqXpi copy

Thank you for your support!

Follow Us!

:(