SARS-CoV-2 Has Ability To Damage Human DNA And Telomeres


Scientists from the University of Vermont-USA along with support from researchers from Duke University School of Medicine-North Carolina-USA have in a new study confirmed that the SARS-CoV-2 coronavirus has the ability able to cause damage to the DNA and telomeres of the human host.

The study findings has alarming implications in terms of long term medical conditions and also helps reason for some of the Long COVID manifestations.

The SARS-CoV-2 coronavirus responsible for the current COVID-19 pandemic that has now infected more than 227 million individuals and caused more than 4.65 million COVID-19 deaths globally according to unreliable official figures (Realistic figures could be as high as eight fold!), is now causing more alarm among physicians and researchers as there seems to be an ever increasing rise in the variety of ailments and medical conditions in those that have been deemed as ‘recovered’ from COVID-19, what is now being termed as Long COVID or Post-Acute Sequelae of COVID-19 (PASC).
More emerging data and Long-COVID News suggest that symptoms and general malaise may continue long after the infection has ended in recovered patients, suggesting that SARS-CoV-2 infection has profound consequences in the human host cells.
The study team reports that SARS-CoV-2 infection can trigger a DNA damage response (DDR) in African green monkey kidney cells (Vero E6).
The team observed a transcriptional upregulation of the Ataxia telangiectasia and Rad3 related protein (ATR) in infected cells.
Furthermore, the study team also observed enhanced phosphorylation of CHK1, a downstream effector of the ATR DNA damage response, as well as H2AX. Strikingly, SARS-CoV-2 infection lowered the expression of TRF2 shelterin-protein complex, and reduced telomere lengths in infected Vero E6 cells.
Hence the study findings suggest SARS-CoV-2 may have pathological consequences to human host cells beyond evoking an immunopathogenic immune response.
The study findings were published on a preprint server and are currently being peer reviewed.
The study findings confirm that SARS-CoV-2 may have consequences to human host cells beyond evoking an immune response!
Most RNA viruses, such as SAR-CoV-2, are renowned for activating the DNA damage response (DDR) pathway and inducing DNA damage due to their replication cycle within host cells.

The signaling pathways ataxia-telangiectasia mutated (ATM), ataxia-telangiectasia and RAD3-related (ATR), and DNA protein kinase (DNA-PK) mediate the DDR. The DDR pathway functions as a crucial part of an intracellular defense system that activates when lesions are detected on the DNA to aid in the repairing of damaged DNA.
It is important to note that when there is a failure in DNA repair, apoptosis is induced, or DNA damage tolerance or translesion synthesis (TLS) is activated, which permits the cell’s survival even though DNA damage is present.
The study team examined the ability of SARS-CoV-2 to impact DNA damage response and telomere stability in Vero E6 cells.
For the study, Vero E6 cells were infected with SARS-CoV-2 and incubated for 48 hours before further downstream processing. The Vero E6 cells were incubated for 10 minutes with RLT buffer containing 2-Mercaptoethanol, to extract the RNA from the infected cell lysates.
The study team then harvested RNA and subjected it to quantification via the Nanodrop 2000. (A ThermoFisher  spectrophotometer). Then it was diluted until the concentration of RNA was 10ng/µl in each sample. Quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) was then performed. Telomere lengths were then measured using primers that detect telomeric repeats.

The study finding showed that following the infection with SARS-CoV-2, the ATR DDR was activated. A substantial increase in the transcription expression of ATR and checkpoint kinase 1 (CHK1), the downstream effector molecule of ATR, and elevated phosphorylation of CHK1 protein, indicated activated ATR DDR.

Within infected cells, there was no increase of the total ATR protein levels or phosphorylation of the ATR protein, which suggests the comprehensive elevation in ATR levels corresponding to the elevated mRNA levels could have materialized before the 48-hour testing time.
Furthermore the levels of CHK1 protein and total ATR were observed to be reduced at 48 hours.
Significantly H2AX phosphorylation protein was also observed to increase, despite an insufficient increase in ATM transcript expression. It was concluded that the ATR DDR pathway is activated in host cells when a SARS-CoV-2 infection occurs, which may impart an unknown proliferation potential to its infectious cycle.
Past studies have shown that breaks in the host double-strand DNA drive ATR activation with retroviral infections such as HIV during viral DNA integration, which leaves single-strand gaps. Infectious bronchitis virus (IBV), an RNA virus of the same family as SARS-CoV-2, has been shown to manipulate the ATR DDR to propel their infection cycle.
Alarmingly as well, it was observed that within 48 hours, the telomere lengths within SARS-CoV-2 infected cells had relatively shortened compared with the uninfected control cells. Also, the expression of TRF2, which functions to protect telomers, was significantly suppressed in the SARS-CoV-2 infected cells.
The study findings has enormous and alarming implications on the future medical and health conditions of so called “recovered” SARS-CoV-2 infected individuals. It is now becoming vital that the pathobiological consequences in recovered patients are studied, especially with the continuous emergence of new strains.
The study findings confirms that SARS-CoV-2 infections are affects telomere function and triggers ATR DDR, which are closely associated with genome stability in human host.
To date there are no known therapeutics to treat Long COVID or PASC, Thailand Medical News is working with research teams across the world to develop a new line of nano-technology based phytochemicals involving polyphenols, organosulfur/organoselenium compounds, indoles, sesquiterpene lactones, ursolic acid and anacardic acid with a key focus epigallocathecin gallate, carvacrol, galangin, limonene, lycopene, naringin, puerarin, terpinene and thymol.
We highly recommend that in the meanwhile, individuals start low doses of Oregano Oil, Quercetin and Skullcap supplements.
Only stick to brands such as Vitaly Works, North American Herb & Spice, Natural factors, Solaray, Gaia Herbs, Thorne Research, Doctor’s Best and Natures Way. Be careful as many American, British and Thai supplement brands are simply peddling inferior or sub-standard products, hence we recommend readers to only stick to the above brands. (We do not have any business interest with any of these brands nor do we receive any monies from any of these brands.)

The current COVID-19 pandemic ( is produced by the SARS-CoV-2 virus, a novel zoonotic Coronavirus of the betacoronavirus genus that most likely crossed species from bats to humans leading to a pneumonia outbreak initially reported in Wuhan, China and now affecting the majority of countries. SARS-CoV-2 causes from mild flu-like symptoms in approximately 80% of the cases to a severe lung and multi-organic failure which can result in death of a significant percentage of patients.

Pathologies associated with SARS-CoV-2 include severe lung failure, diarrhea, heart infarct, and brain pathologies among others [1–3]. This wide viral tropism is mediated by expression of the Angiotensin-converting enzyme 2 (ACE2), which acts as the receptor protein for the virus to enter the host cells. In particular, the SARS-CoV-2 spike protein directly binds the ACE2 human protein [4–7]. The human ACE protein is expressed in alveolar type II (ATII) cells in the lung [8], as well as in the kidney, the heart and the gut [9–14].

This expression pattern of the ACE protein explains that a preferential site for SARS-CoV-2 infection is the lung [4, 15, 16], although the virus can also infect kidney, intestine, and heart cells causing severe pathologies in all these tissues [1–3, 11, 17, 18]. In this regard, it caught our attention that a common outcome of SARS-CoV-2 infection seems to be induction of fibrosis-like phenotypes in the lung and kidney, suggesting that the viral infection maybe exhausting the regenerative potential of tissues [11, 16–18].

In contrast to influenza infection, that causes a high mortality in infants [19–24], SARS-CoV-2 infection causes low mortality in infants or children but results in a progressively increased mortality with increasing age reaching up to 15% mortality in individuals that are ≥80 years old (see for mortality data in Spain).

These findings suggest that molecular mechanisms at the origin of organismal aging maybe influencing the outcome of SARS-CoV-2 infection by increasing lethality. One of such molecular events underlying aging is the progressive shortening of telomeres throughout life, which can cause exhaustion of the proliferative potential of stem cells and immune cells among others [25–27].

Telomeres are specialized structures at the chromosome ends, which are essential for chromosome-end protection and genomic stability [28]. Vertebrate telomeres consist of tandem repeats of the TTAGGG DNA sequence bound by a six-protein complex known as shelterin, which prevents chromosome end-to-end fusions and telomere fragility [29, 30].

As cells divide and DNA has to be replicated, telomeres become progressively shorter owing to the so-called “end replication problem” [31, 32]. Thus, telomere shortening occurs associated with increasing age in humans [33], mice [34] and other species, and the rate of telomere shortening has been shown to correlate with species lifespan [35].

When telomeres become critically short this results in loss of telomere protection, leading to activation of a persistent DNA damage response [36] and loss of cellular viability by induction of apoptosis and/or senescence [30].

Telomerase is a reverse transcriptase that is able to elongate telomeres de novo by adding TTAGGG repeats to chromosome ends [37]. Telomerase is active in embryonic stem cells, thereby ensuring sufficiently long telomeres with generations in a given species. After birth, however, telomerase expression is silenced in the majority of cell types causing telomeres to shorten with age.

We have shown by using telomerase-deficient mice with critically short telomeres, that short telomeres are sufficient to impair the ability of stem cells to regenerate different tissues, including skin, brain and bone marrow [38–41]. In humans, mutations in telomerase or telomere-binding proteins can also lead to very short telomeres and appearance of pathologies characterized by loss of the regenerative capacity of tissues and presence of fibrosis in lungs, liver or kidney, as well as by intestinal atrophy and bone marrow aplasia [42].

In particular, we previously demonstrated that short or dysfunctional telomeres are at the origin of pulmonary fibrosis in mouse models of the disease [43]. In particular, induction of telomere dysfunction specifically in alveolar type II (ATII) cells by deletion of an essential telomere protective protein in these cells, TRF1, is sufficient to induce progressive and lethal pulmonary fibrosis phenotypes in mice, which are concomitant with induction of telomeric DNA damage, cell death and senescence [43].

These findings demonstrate that dysfunctional telomeres in lungs ATII cells lead to loss of viability of these cells and induction of fibrosis. Also in support of this notion, we have demonstrated that therapies aimed to elongate telomeres, such as a telomerase gene therapy using adeno-associated vectors (AAV9-TERT) can stop the progression of pulmonary fibrosis associated to short telomeres in mouse models of the disease by increasing telomere length in ATII cells, as well as their proliferative potential [44], thus demonstrating the importance of sufficiently long telomeres to allow tissue regeneration.

Importantly, as SARS-CoV-2 infects different cell types in humans, including ATII cells in the lungs, it is plausible that viral infection could damage these different cell types forcing an increased turn-over of different regenerative cell types.

While in young individuals with sufficiently long telomeres, regenerative cell types, such as lung ATII cells could undergo these extra cell divisions and contribute to tissue healing, older individuals with shorter telomeres may fail to allow cell proliferation and regeneration, thus leading to tissue failure.

Thus, here we set to assess whether telomere length in COVID-19 patients correlated with development of more severe COVID-19 pathologies.

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