The use of proteomics may improve the therapeutic approach to COVID-19

A research group in India recently explained how the field of proteomics is crucial in helping to tackle the current pandemic of coronavirus disease 2019 (COVID-19).

The outbreak of COVID-19 has been a pandemic since it was declared pandemic by the World Health Organization (WHO) on March 11.^thIn 2020, scientists have been working on the development of treatments for the prevention and treatment of the causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The development of therapeutic and preventive strategies requires an accurate understanding of the role that proteins play in the SARS-CoV-2 infection process and the progression of COVID-19.

Rashmi Rana and colleagues from the research division at Sirgangaram Hospital in New Delhi say that this vast area of ​​proteomics has enough technology to tackle this challenge.

In a recent overview published in Journal of Proteins and Proteomics, Lana and the team not only accelerated progress in coping with the previous coronavirus pandemic, but also developed some of the proteome technologies that could prove to be invaluable in tackling the current COVID-19 crisis. I emphasize it.

Challenges posed by the unprecedented spread of SARS-CoV-2

The new coronavirus SARS-CoV-2 was recently added to the other six groups. Coronavirus It can also infect people, including SARS-CoV-1, the agent that caused the outbreak of SARS between 2002 and 2003.

However, SARS-CoV-2 infection appears unstoppable, resulting in unprecedented global infection and mortality rates, especially given the high proportion of asymptomatic carriers. It has proven to be particularly difficult.

The majority of patients have mild or no symptoms, but about 20% develop severe illness and can cause symptoms such as pneumonia and respiratory failure.

“Patients with these clinical symptoms are already in a clinically critical stage and require immediate access to a specialized intensive care unit. Otherwise, they may die rapidly. “The researchers write. Therefore, they add, it is important to develop new approaches that can predict and treat cases that may progress to clinically serious disease.

Such strategies focus primarily on proteins involved in SARS-CoV-2 infection, rather than nucleic acids. However, while many of the technologies available to date are effective in counting genes that are differentially expressed, the proteins involved and the functional role these proteins play in the progression of infection and disease. Often cannot be identified.

How can proteomics help?

A variety of identification and separation techniques allow the separation of proteins from complex mixtures, facilitating analysis of protein-protein interactions, temporal expression patterns, cell or intracellular distribution, and more.

While the most common separation methods are one-dimensional and two-dimensional gel electrophoresis and high performance liquid chromatography, mass spectrometry (MS) forms the backbone for protein detection and identification.

Protein identification using MS technology overcomes the limitations of other proteomics techniques (including 2D gel electrophoresis) that require large amounts of purified protein for analysis.

Contribution of conventional MS-based technology

MS-based viral peptide detection was previously used to profile viral proteins that affect the respiratory pathways.

A study that analyzed convalescent sera in SARS patients using matrix-assisted laser desorption / ionization time-of-flight mass spectrometry (MALDI-TOF MS) found a novel nucleocapsid that was later established as a major SARS-CoV-1 immunogen. The protein has been identified.

Currently, reverse transcription-polymerase chain reaction (RT-PCR) is the primary method used to detect viral genes in COVID-19-positive patients. However, the high variability of SARS-CoV-2 may mean that RT-PCR is not sensitive enough to detect these genes. In addition, this technique has a long reaction time, resulting in low throughput.

MS-based detection, on the other hand, can provide easy and rapid detection of SARS-CoV-2, even among recovered patients.

Peptides with SARS-CoV-2 structure were detected by a technique called multiple reaction monitoring mass spectrometry (MRM-MS). Spike protein With 90% sensitivity and 100% specificity among recovered patients tested for virus negative by RT-PCR.

Protein microarrays may also help improve diagnosis

Protein microarrays are another valuable platform for detecting viral peptides in protein complexes.

In one recent study, the opt-microfluidic sensing platform detected antibodies against SARS-CoV-2 spike proteins in diluted human plasma with high sensitivity and rapidity. This is a development that can significantly improve diagnostics.

Rana et al. To determine how a comparative study of patients at different stages of SARS-CoV-2 infection progresses towards severe or life-threatening symptoms in severe or asymptomatic patients. It states that it is urgently needed.

A recent study used single molecule array technology to study quantitative proteomes of SARS-CoV-2 spike proteins, S1 spike subunits, and nucleocapsid proteins in the plasma of COVID-19 patients.

The study, which first detected these SARS-CoV-2 antigens in the blood, revealed that the antigens were associated with disease progression.

What does proteomics mean in the future?

The vast field of proteomics can generate information that leads to improved interpretations of the processes involved in SARS-CoV-2 infection and disease progression.

“For decades, proteomics has proved its diversity. Effectiveness For the development of new potential drug discovery targets for the ever-emergence of diseases that challenge humanity, “Lana and colleagues write.

In the context of COVID-19, proteomics helps to uncover new biomarkers and define point-of-care procedures that mean that cost-effective medical care can be provided closer to the patient’s home.

“In this developing country, there are more effective care challenges for SARS-CoV-2, and point-of-care testing could play a much larger role here in the future,” the team concludes. ..