Learning how SARS-CoV2 hijacks and damages lung cells

Learning how SARS-CoV2 hijacks and damages lung cells

The emergence of the SARS-CoV2 virus has caused turmoil across the globe, forcing the researchers to study it in more detail. However, the behavior of the virus has been quite notorious. The frequent mutations and very less prior knowledge has caused some obstacles. However, scientists were acquainted that if they understand the underlying pathways in lung cells and host protein being impacted during the viral infection then there can be chances of identifying potential solutions. Considering this, scientists have recently found out how SARS-CoV2 hijacks and damages the lung cells.

The study was a multi-group collaboration between the Center for Network Systems Biology (CNSB), Center for Regenerative Medicine (CReM), and National Emerging Infectious Disease Laboratory (NEIDL). The researchers have mapped the molecular responses emerging from lung cells infected with the SAR-CoV2 virus. The finding of the study has been published in the Journal of Molecular Cell.

To understand the disease pathology and gain new insights to discover potential therapeutic targets, the researchers bioengineered the human alveolar cells. The cells when combined with high-end mass spectroscopy technology, it helped the researchers to identify potential host proteins and pathways changing during SARS-CoV2 infection. The researchers found out that lung cells infected with SAR-CoV2 have abnormal phosphorylation.

Phosphorylation is a very crucial protein modification process contributing to protein functionality in the cells. The proper phosphorylation process is important for healthy cells. However, it was noticed that the infection alters this process leading to cascading abnormal changes. These changes increase the chances of the virus to thrive within the cells and eventually destroy it.

The study also showed that as soon as the virus encounters the lung cells, it initiates exploiting the resources required for the normal functioning and growth of the cell. The invasion of the virus further disrupts the functioning of the cell and damaging it extensively. The resources used, powers the virus eventually leading to rapid proliferation and expansion in nearby regions. As a result, the exhausted and damaged cells undergo self-destruction and the virus starts infecting the cells in the vicinity while evading the body’s immune system. This cycle repeats continuously leading to the hijacking of lung cells and widespread damage.

The researchers examined lung alveolar cells from one to 24 hours after infection with SARS-CoV-2 to understand what changes occur in lung cells immediately (at one, three, and six hours after infection by SARS-CoV-2) and what changes occur later (at 24 hours after infection). These changes were then compared to uninfected cells. All proteins from infected and uninfected alveolar cells, corresponding to the different time-points were extracted and labeled with unique barcoding tags called “tandem mass tag.” These tags, which can be accurately detected only by a mass spectrometer, permit robust quantification of protein and phosphorylation abundance in cells.

“Our results showed that in comparison to normal/uninfected lung cells, SARS-CoV-2 infected lung cells showed dramatic changes in the abundance of thousands of proteins and phosphorylation events,” said Darrell Kotton, MD, BUSM, CReM.

“Moreover, our data also showed that the SARS-CoV-2 virus induces a significant number of these changes as early as one-hour post-infection and lays the foundation for a complete hijack of the host lung cells,” adds Elke Mehlberger, PhD, NEIDL.

Scientists also tried to examine the data obtained from the study to identify any potential opportunities for COVID-19 treatment. They found that about more than 18 existing drugs that have been already clinically approved can be re-purposed for the treatment. The research team believes that the current findings are very crucial and can contribute a lot to the field, specifically in terms of devising a cost-effective, robust and life-saving treatment to overcome COVID-19.


Breakthrough: 2003 SARS survivor antibody, a potential cure for COVID-19

Breakthrough: 2003 SARS survivor antibody, a potential cure for COVID-19.

With the number of COVID-19 cases surpassing 4.3 million worldwide and counting, scientists are working around the clock in efforts to develop vaccines and treatments to slow the pandemic. Currently, scientists are looking into whether existing drugs might work or whether new treatments need to be developed to try and tackle the virus. 

In this article, we discuss the latest scientific finding, how an antibody identified in a survivor of the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak has the potential to neutralize COVID-19, providing a glimmer of hope in this current battle.

How do these antibodies work against COVID-19?

Development of immunity to a pathogen through natural infection is usually a multi-step process taking around 1-2 weeks. The body immediately reacts to fight the infection with a nonspecific innate response which will slow the progress of the virus and may even prevent it from causing symptoms. This is then followed by an adaptive response where the body produces antibodies specifically binding to the virus and eliminate it along with the cells infected. 

Recently a research team came forward and publisher a paper stating that they have identified an antibody from a patient recovered from SARS 2003, which can potentially inhibit the cause of COVID-19. The antibody S309 is now on a fast track development and testing at Vir Biotechnology. 

The scientists first identified monoclonal antibodies from the memory B cells of the SARS survivor. The memory B cells reproduce cells and have a long lineage, sometimes for life. The cells have the tendency to remember a pathogen or one similar to it and have the potential to fight against it in the future if re-infected.  

The S309 antibody, in particular, is directed at a protein structure of the coronaviruses. The structure is essential for the virus, to recognize a host cell receptor and infect it. This particular infectivity capability is present in the spikes that crown the virus. S309, in particular, attacks the spike- disabling it, hence hindering the coronavirus to enter the cells. It should also be noted that the antibody showed the capability to target binding sites of several sarbocoviruses, not just COVID-19 and SARS. 

What next- Will this be the breakthrough we all are hoping for COVID-19?

In this paper titled “Cross-neutralization of SARS-CoV and SARS-CoV2 by a human monoclonal antibody”, scientists have reported that by combining the S309 antibody with other similar antibodies identified in the recovered SARS survivor, there is a chance of neutralizing the COVID-19 virus. This cocktail of antibodies could be the answer to limit the coronavirus from forming mutants capable of escaping the single ingredient antibody. 

“We still need to show that this antibody is protective in living systems, which has not yet been done,” said David Veesler senior author. “Right now there are no approved tools or licensed therapeutics proven to fight against the coronavirus that causes COVID-19”, he added. 

At this point in the pandemic, there is not enough evidence to prove the effect of antibody-mediated immunity against the virus. It cannot guarantee an immunity passport or a risk-free certificate. Further research and studies need to be performed before we can reach a conclusion. 


FDA approves the first saliva test for COVID-19 testing

FDA approves the first saliva test for COVID-19 testing

With a rising death toll across the globe, researchers are looking for ways to develop highly effective detection tests for early diagnosis of COVID-19. Though there are tests based on the nasal swabs, other alternative methods like saliva-based tests can prove to be highly robust. In light of this, scientists have created an easy test that uses saliva instead of the nasal swabs as a sample.

The US Food and Drug Administration approved the first saliva test for COVID-19 testing for emergency early this month, which can be used as an alternative to existing tests.

“Considering the high transmission rates of coronavirus and rising cases, it is very crucial to have all types of testing options to carry out as much testing as possible in any form. The only way one can prevent the spread of coronavirus virus is by mass testing and self- isolation”, said by one of the researchers working on infectious disease and pandemic preparedness at the Johns Hopkins University.

Why lookout for alternatives?

Presently, COVID-19 testing involves the use of nasal swabs based tests where health professionals need to insert a swab into each nostril, reaching out at the back of the nasal cavity where the nasopharynx is located. The swab is gently scraped over the tissues to collect the sample and later sent for the analysis. Though the present method is robust, it proved to be very cumbersome to an extent. The nasal swab based testing requires highly professional health practitioners to perform the sample collection. In the present time where we are facing the shortage of healthcare professionals, the nasal swabs based tests increase the burden further. Moreover, extra precautions are needed to carry out this test, which includes wearing fresh gloves, personal protective equipment, and face shield that are in short supply.

On the other side, the collection of saliva samples is quite easy and can be performed by any individual without the requirement of expertise.  Saliva tests have been used in the market for the various genetic tests and are quite common to people. The process involves thoroughly cleaning the hands and spitting the saliva sample into the collection tube up to the mark indicated. The entire process is very easy and doesn’t require a large number of safety requirements such as PPE. However, as per the recent guidelines shared by Food and Drug Administration (FDA), saliva-based testing will still be carried out in the healthcare setting under the guidance and supervision of expert & qualified healthcare professionals.

Saliva testing – a robust alternative

“Saliva testing will help with the global shortage of swabs for sampling and increase testing of patients, and it will not require health care professionals to be put at risk to collect samples,” Andrew Brooks, the chief operating officer of RUCDR Infinite Biologics, a biorepository backed by Rutgers University that developed the spit test, explains in a statement.

The saliva-based testing uses TaqPath Sars-CoV2 Assay which is used in existing coronavirus tests for identifying the viral RNA. Scientists shared that apart from identifying the potential carriers of the COVID-19 virus, the present saliva-based testing can help in re-testing the people who have shown recovery to help them end the self-isolation.

Way ahead

To assess the robustness of the saliva-based test for COVID-19 detection, researchers collected 60 samples from COVID-29 patients using the saliva swab tests. The results for Sars-CoV2 RNA in these saliva samples showed the same results as conventional nasal swab based tests taken from the same infected patients. This highlights the robustness and effectiveness of saliva as high as a nasal based test without any false-negative results.