Combating of COVID-19 by Proteomics

Introduction

SARS-CoV-2 becomes a global challenge after it hits millions of deaths worldwide. Researchers from different parts of the world are doing vaccine trials against COVID-19. World Health Organization announced that the only way to reduce COVID-19 cases is by taking precautionary measures and maintaining social distances until an effective vaccine is produced. Many countries throughout the World also control the number of increasing cases by following these precautions. As scientists are trying to develop vaccines, they are also doing research on the structure, function and pathway of coronavirus when it attacks the host cells with the help of proteomics and multi-omics studies.

Coronavirus and Proteomics

In 2019, novel coronavirus was emerged as a pandemic flu from Wuhan city, China and spread throughout the world. The main source of transmission of SARS-CoV-2 is contact with the infected patient via sneezing and coughing because of his/her respiratory droplets contains same variants of infection which can transform to another healthy person. It can also transform indirectly in the form of aerosols and contaminated surfaces. [1]

Multi-omics research on COVID-19

With the help of multi-omics research e.g., genomics and proteomics researchers have successfully sequenced the genome and structure of SARS-CoV-2. Phylogenetic studies show that novel corona have 80% similar genome with the previous SARS-CoV which was emerged from 2002-2004 in China. It was also revealed that it has similarity with the Middle East Respiratory Syndrome MERS which was camel flu spread in Saudi Arabia having 34% fatality rate. All these three viral pathogens belong to similar coronavirus family and research shows that their origin was pangolin and bats.

Severe Acute Respiratory Syndrome SARS-CoV-2 belongs to beta-coronavirus genus mutated from intermediate specie Rhinolophus affinis of bats having 96% genome similarity with human n-CoV. Its mortality rate is high as compared to previous ones because its rate of transformation is high and antibodies do not develop against these strains.

Different microscopic studies show that Covid-19 have the following major components:

• Viral envelope contains spike, envelope and membrane proteins which appear as crown-like structure of the virion
• Nucleocapsid contains +ve single-stranded RNA genome with 30,000 bp in length.
• Diameter 50-200nm. [2]

 

How Proteomics help to combat COVID-19

Proteomics is the study of proteome at large scale and proteome is the entire protein part of any cell, tissue or whole organisms. It includes many techniques and methods to study and reveal the proteins structure, functions and all the interactions protein used to bind with other biological molecules. As 2019 n-CoV also uses its spike protein to bind on receptor cells of host cells, so different techniques in proteomics research pave the way to combat viral infections by developing therapeutics and diagnostic techniques. NMR spectroscopy and X-ray crystallography is used to study the 3D shapes and structures of small microscopic particles but due to some limitations, these techniques are not efficiently used to detect and study viral particles. In fact, Cryo-electron microscopy, affinity-based mass spectroscopy and anti-body assays are used to successfully study the viral particles. Recently, Chinese researchers used Cryo-EM to reveal COVID-19 structure.

Cryo-Electron Microscopy

Cryogenic EM is a type of electron microscopy in which samples (microorganisms, biological molecules and viruses etc.) are cooled down at cryogenic temperatures and then placed in the vitreous ice water (an amorphous form of ice). After that sample is seen under transmission electron microscopy in the form of high-resolution 2D and 3D representation of biological samples.

When a group of scientists from China studied the structure and function of COVID-19 under cryo-EM, the following information, was revealed;

• The Spike protein on the outer membrane of n-CoV contains two subunits i.e. S1 and S2 responsible for the initial attachment and fusion with the membrane of a host cell.
• SARS-CoV-2 uses Angiotensin-converting enzyme 2 (ACE2) to enter into the human host cell because it acts as a receptor protein for coronavirus.
• ACE2 binds to n-CoV ten times more strongly than the previous SARS viruses.
• The trimeric spike glycoprotein on the envelope of coronavirus is the key feature for the development of diagnostic techniques and therapies because it tells about the initial pathway of virion entry into host receptor cells.
• When three antibodies of previous SARS-CoV were bound to the new corona virus, detection of binding did not occur. This study unveils that it needs new antibodies to get attached with it which gives initial information for the development of vaccines against COVID-19.
• Cryo-EM gives 3.5-angstrom high resolution of SARS-CoV-2.
• COVID-19 when entering into the host cell, it takes control of the host cell machinery producing its own copies and shutdowns the immune response. [3]

Mass Spectrometry

Researchers use Affinity-purification Mass Spectrometry to study the protein-protein interaction map of SARS-CoV-2 and human receptors cells. The result shows 332 SARS-CoV-2 and human protein interactions out of which 66 proteins of the human cell could be recognized and targeted by several drugs declared by the FDA. This host-pathogen interactions analyses could lead to the production of effective therapeutic drugs and vaccines.

Antibody-Based Assays

Humoral immunity against viral pathogens such as COVID-19 could help to produce therapeutic and diagnostic measure with the development of antibody-based assays. Proteome microarray of SARS-CoV-2 leads towards the mapping of its antibody interactions. Scientists discovered that some serological antibodies may be used to inhibit or neutralize the binding of spike protein to ACE2 receptor cells. Some other commercially available antibodies could also be helpful in binding with COVID-19 proteins and thus inhibit its entry into specific host cells.

• Chemiluminescence immunoassay (CLIA) is one of the types of antibody-based assays. It is used for the qualitative detection and distinction of antibodies i.e. IgM and IgG against COVID-19 pathogen present in human blood serum.
• Molecular docking was also used to analyze the interactions between several ligands and COVID-19 receptors. This study was helpful because it reveals that several antimalarial drugs such as Metaquine and anti-HIV i.e. antiretroviral Saquinavir are potential factors in targeting drugs for SARS-CoV-2 because these candidates have specific interactions with the pathogen receptors. [4][5]

Proteomics thus playing an important role in producing vaccines, therapeutic drugs and diagnostic techniques to fight against COVID-19 and other related pathogens.

By: Maryam Baig

References

1. https://www.who.int/emergencies/diseases/novel-coronavirus-2019
2. Bharadwaj, A., Wahi, N., Saxena, A., & Choudhary, D. (2020). Proteome Organization of COVID-19: Illustrating Targets for Vaccine Development. J Pure Appl Microbiol, 14(suppl 1), 831-840.
3. Ray, S., & Srivastava, S. (2020). COVID-19 Pandemic: Hopes from Proteomics and Multiomics Research. OMICS: A Journal of Integrative Biology
4. Wang, H., Hou, X., Wu, X., Liang, T., Zhang, X., Wang, D., ... & Li, Y. (2020). SARS-CoV-2 proteome microarray for mapping COVID-19 antibody interactions at amino acid resolution.
5. Messner, C. B., Demichev, V., Wendisch, D., Michalick, L., White, M., Freiwald, A., ... & Ludwig, D. (2020). Ultra-high-throughput clinical proteomics reveals classifiers of COVID-19 infection. Cell systems, 11(1), 11-24.