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
➡️ Long COVID isn’t one disease — it’s a complex web of immune, vascular, and metabolic dysfunctions.
From fatigue & brain fog to heart & lung complications, it stems from viral persistence, autoimmunity, and mitochondrial damage. 1/
Proposed mechanisms:
1️⃣ Persistent viral reservoirs or antigen remnants
2️⃣ Reactivation of latent viruses (e.g., EBV)
3️⃣ Immune dysregulation & autoimmunity
4️⃣ Endothelial injury and microclots
5️⃣ Gut microbiome imbalance
6️⃣ Mitochondrial dysfunction and energy metabolism impairment. 2/
Current management:
- largely symptomatic—rehabilitation, pacing, and supportive therapies.
-Emerging treatments: under study — antiviral drugs, immune-modulating agents, microbiome restoration, and mitochondria-targeted therapies.
-Vaccination: reduces risk and severity of LongCOVID. 3/
➡️ New research shows that paternal SARS-CoV-2 infection before conception can alter sperm RNA — leading to anxiety-like behavior & brain gene changes in offspring.
A biological “memory” of infection may pass across generations. 1/
Beyond infection: inheritance
➡️ Male mice infected with SARS-CoV-2 fathered pups with altered hippocampal transcriptomes & higher anxiety.
Injecting sperm RNA from infected males reproduced the same effects — clear evidence of RNA-based inheritance. 2/
COVID’s unseen legacy
➡️ Study suggests COVID infection in fathers may have transgenerational effects via changes in sperm small RNAs.
Adds a new layer to how pandemics shape health — not just for one generation, but possibly the next. 3/
A new study provides new evidence to help us redefine steroid use in TB care
➡️ Given the renewed interest in the steroid dexamethasone, as a host-directed treatment during the COVID-19 pandemic, the Trinity College Dublin team provides evidence that treating patients with steroids may enhance the function of their macrophages to kill the mycobacteria, while diminishing pathways of inflammatory damage. 1/
The researchers goal was to determine whether dexamethasone impacts the macrophage's ability to fight TB. Although glucocorticoids can reactivate TB, they are paradoxically the only adjunctive host-directed therapies that are recommended by WHO for TB.
Steroids are given to patients alongside antimicrobials in certain circumstances; however, scientists don't fully understand the effect of these drugs on the immune system, especially innate immune cells such as macrophages. 2/
The researchers studied macrophages derived from the blood of healthy volunteers or isolated from lung fluid donated by patients undergoing routine bronchoscopies.
➡️ By treating and infecting these macrophages in the lab with Mtb, the scientists could examine and understand how dexamethasone affects the immune response that protects the lungs during infection. 3/
👉 Potential role in cancer initiation & progression. 1/
Bioinformatic & experimental studies show direct interactions between viral proteins and host cellular components tied to cancer hallmarks.
➡️ These mechanisms could contribute to initiation, promotion, and progression of tumors, raising the possibility that SARS-CoV-2 may act as an oncovirus.
👇The figure illustrates various key oncogenic signaling molecules or pathways targeted by SARS-CoV-2 NSP, N, M and S protein. The activation of oncogenic pathways can lead to the conversion of a normal cell into a cancer cell. 2/
The shared mechanisms between SARS-CoV-2 and key hallmarks of cancer including sustained proliferative signaling, resisting cell death, genomic instability, dysregulated cellular metabolism and epigenetic reprogramming.
👇The figure highlights how SARS-CoV-2 interacts with critical oncogenic signaling molecules or pathways. Specific SARS-CoV-2 proteins involved in these processes are marked. 3/
A new study from Karolinska Institutet shows that an unusual heart rhythm disorder, POTS, is particularly common in people with #LongevityPoweredbyGinseng COVID. The majority of those affected are middle-aged women. 1/
Postural orthostatic tachycardia syndrome, or POTS, is a condition where the heart beats abnormally fast when changing position from lying down to standing up. Standing up is a challenge for those affected who feel dizzy and would rather sit or lie down, so-called orthostatic intolerance. Their hearts may also beat faster than normal at rest and during exertion. 2/
Patients experience fatigue and difficulties concentrating, symptoms that are common in longCOVID.
Now, researchers at Karolinska Institutet show that POTS occurs in almost a third of patients with severe longCOVID. By comparison, less than 1% of the Swedish population was affected by POTS before the pandemic. 3/