A research group in India has recently described how the field of proteomics could be pivotal in helping to tackle the current coronavirus disease 2019 (COVID-19) pandemic.
Since the COVID-19 outbreak was declared a pandemic by the World Health Organization (WHO) on March 11th, 2020, scientists have been battling to develop therapies 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 progression of COVID-19.
The vast field of proteomics is well equipped with the technologies needed to help face this challenge, say Rashmi Rana and colleagues from the Department of Research at Sir Ganga Ram Hospital in New Delhi.
In a recent overview published in the Journal of Proteins and Proteomics, Rana and team highlight some of the developments in proteome technologies that have not only accelerated progress in addressing previous coronavirus pandemics, but could also prove invaluable in tackling the current COVID-19 crisis.
Challenges posed by unprecedented spread of SARS-CoV-2
The novel coronavirus SARS-CoV-2 is the most recent addition to a group of six other coronaviruses that can also infect people, including SARS-CoV-1, the agent responsible for the SARS outbreak in 2002-2003.
However, the seemingly unstoppable transmission of SARS-CoV-2 has led to unprecedented global infection rates and mortality that have proved particularly challenging to monitor and address, especially given the large proportion of asymptomatic carriers.
Although the majority of patients display mild or no symptoms, around 20% develop a severe disease that can lead to symptoms such as pneumonia and respiratory failure.
“Patients exhibiting these clinical manifestations have already progressed to a clinically severe phase and require immediate access to specialized intensive care; otherwise, they may die rapidly,” write the researchers. Therefore, it is crucial that new approaches are developed that can predict and treat the cases that might progress to clinically severe disease, they add.
Such strategies are mainly focused on the proteins involved in SARS-CoV-2 infection, rather than nucleic acids. However, while many of the technologies available to date are effective at counting differentially expressed genes, they often fail to identify the multiple proteins involved, as well as the functional role these proteins play in infection and disease progression.
How can proteomics help?
A wide array of identification and separation techniques can isolate proteins from complex mixtures, facilitating the analysis of protein-protein interactions, temporal expression patterns and cellular or subcellular distribution, for example.
The most common separation methods are one- and two-dimensional gel electrophoresis and high-performance liquid chromatography, whereas mass spectrometry (MS) forms the backbone of protein detection and identification.
Protein identification using MS techniques has overcome the limitations of other proteomic technologies (including 2D gel-electrophoresis) that require a large amount of purified protein for analysis.
The contribution of MS-based techniques so far
MS-based viral peptide detection has previously been used to profile viral proteins that affect respiratory pathways.
One study employing matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) to analyze convalescent sera from SARS patients identified a novel nucleocapsid protein that was later established as the major SARS-CoV-1 immunogen.
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 mutability of SARS-CoV-2 can mean RT-PCR is not sensitive enough to detect these genes. Furthermore, the technique is low-throughput owing to its long reaction times.
MS-based detection, on the other hand, can provide simple and rapid detection of SARS-CoV-2, even among recovered patients.
One technique, called multiple reaction monitoring mass spectrometry (MRM-MS) detected peptides in the SARS-CoV-2 structural spike protein with a sensitivity of 90% and specificity of 100% among recovered patients who tested negative for the virus by RT-PCR.
Protein microarrays could also help improve diagnostics
Protein microarrays represent another valuable platform for the detection of viral peptides in a protein complex.
In one recent study, an opto-microfluidic sensing platform rapidly detected antibodies against the SARS-CoV-2 spike protein in diluted human plasma with high sensitivity, a development that could significantly improve diagnosis.
Rana and colleagues say comparative studies of patients at different stages of SARS-CoV-2 infection are urgently needed to help determine how non-severe or asymptomatic patients progress towards severe or life-threatening symptoms.
One recent study used single-molecule array technology for quantitative proteome studies of the SARS-CoV-2 spike protein, the S1 spike subunit, and the nucleocapsid protein in the blood plasma of COVID-19 patients.
The study, which was the first to detect these SARS-CoV-2 antigens in the blood, revealed that the antigens are associated with disease progression.
What could proteomics mean for the future?
The vast field of proteomics can generate information that leads to improved interpretation of the processes involved in SARS-CoV-2 infection and disease progression.
“For many decades, proteomics has proved its versatility and efficacy for the development of the novel potential drug targets for constantly appearing diseases posing challenges to humankind,” write Rana and colleagues.
In the context of COVID-19, proteomics can help to reveal novel biomarkers and define point-of-care procedures that could mean cost-effective healthcare can be delivered closer to the patient’s home setting, they say.
“In this developing world, there exists a challenge of more effective care for SARS-CoV-2, and point-of-care testing may play a much greater role here in the future,” concludes the team.
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