Structural studies of SARS-CoV-2 nucleocapsid protein

Perspectives in relation to diagnosis and drug design

 A novel zoonotic coronavirus SARS-CoV-2 was originally explored in Wuhan, China in December 2019 and further regarded to the serious pandemic known as COVID-19. In early March 2022, the global COVID-19 pandemic has caused over 453 million confirmed cases and over 6 million deaths (John Hopkins Coronavirus Resource Center, https://coronavirus.jhu.edu).

 The COVID-19 virus and the emergence of new virus variants seriously threat to global public health. It is a strong requirement to develop the effective diagnostic tools which are able to quickly and reliably detect active SARS-CoV-2 infections.

 Structural proteins of the COVID-19 virus are very important to understand its pathogenic mechanism, thus leading to the development of antibodies, vaccines and drugs for targeting these proteins and viruses.

 SARS-CoV-2 comprised the four structural proteins; the spike (S), nucleocapsid (N), envelope (E) proteins and membrane glycoprotein (M). A complete virus particle (virion) is represented in Figure 1. Cryo-electron microscopy is one of the powerful tools to determine the overall structure of the S protein, thus presenting a unique crown or ‘corona’-like shape.

 Three viral proteins; the spike (S), envelope (E) and membrane (M) are embedded in the outer layer of the corona viral particle. The corona viruses protect themselves from the surrounding environment, then the ribonucleic acid (RNA) forms a stable packed in the lipid membrane. The nucleocapsid protein (nucleoprotein) is responsible for tightly wrap the RNA of viruses. However, the fatty membrane of SARS-CoV-2 is sensible to be destroyed by soap, detergent or surfactant.

 The nucleocapsid protein significantly involves in viral genomic RNA binding, thus protecting the coiled RNA as its genetic material inside the virus particle. Moreover, the N protein also plays an important role in the early stages of viral infection when the RNA genome is first released into the target host cell.

 X-ray crystal structures of the N-terminal (PDB entry 7CDZ) and C-terminal domains have been illustrated here (PDB entry 6WZO). Holo structure of N-terminal domain in complex with double strand RNA (PDB entry 7ACS) has been determined by Nuclear Magnetic Resonance Spectroscopy technique.

Read more on the Thai Synchrotron website

Image:  Three dimensional models of the SARS-CoV-2 virion and a schematic diagram of its four structural proteins. 

Credit: Figures were modified from coronavirusexplained     

Women in Science @SLRI

Thailand is home to the Synchrotron Light Research Institute (SLRI) and this week’s #LightSourceSelfie features three of their staff members – Dr Phakkhananan Pakawanit, Beamline Scientist, Dr Prapaiwan Sunwong, Accelerator Physicist, and Supawan Srichan, Engineer. During this enlightening video, they explain their roles, the challenges and what excites them about working at a light source. Dr Sunwong describes a big 7 year project to design and build a new 3.0 Gev synchrotron light source in the Eastern Economic Corridor of Innovation (EECi). In June 2022, SLRI will host the 13th International Particle Accelerator Conference (IPAC’22) in Bangkok. IPAC is the main international event for the worldwide accelerator community and industry. To find out more, visit www.ipac22.org

SLRL’s #LightSourceSelfie

Multifunctional cellulose filter paper for use as electrical nanogenerator

A research team led by Prof. Dr. Naratip Vittayakorn from King Mongkut’s Institute of Technology Ladkrabang successfully developed the multifunctional cellulose filter paper for use as Triboelectric Nanogenerator (TENG). TENG generates electricity when nano surfaces are rubbing or contacting together which can transform mechanical or heat energy at small amount into electricity. Moreover, TENG is a nanomaterial known for its light weight, low price, and high efficiency.

TENG consists of Ti0.8O2nanosheets (Ti0.8O2NSs) which is a dielectric material capable of storing electricity, and Ag nanoparticles (Ag NPs) which has electrical conductivity property. The research team applied the Synchrotron X-ray Tomographic Microscopy (XTM) technique at the XTM end-station, Synchrotron Light Research Institute (Public Organization) to study and analyze the research outcome. By applying this technique, the research team can clearly detect scattering patterns of both Ti0.8O2NSs and Ag NPs in different layers of the filter paper.

Read more on the SLRI website

Image: Figure 1 (a)-(d) showing 3D graphic photos gained from applying Synchrotron XTM technique on each layer of composite film in the multifunctional cellulose filter paper consisting of 3 Ti0.8O2NSs layers and 5 Ag NPs layers (scattering patterns of PDMS, the multifunctional cellulose filter paper, Ti0.8O2NSs, and Ag NPs were shown in purple, yellow, light blue, and red, respectively).

Innovations against COVID-19 outbreak presented to MHESI Minister

Adjunct Prof. Dr. Anek Laothamatas, the Minister of Higher Education, Science, and Innovation (MHESI), Thailand, had a visit to the field hospital at Suranaree University of Technology (SUT), Nakhon Ratchasima, on Thursday, 22 April 2021.  On this occasion, the Minister visited an exhibition on innovations created and presented by SLRI to prevent the spread of COVID-19 at SUT Administration Building.  

 In supporting the handling of COVID-19 situation, SLRI researchers created outstanding various innovations.  The first innovation is studying and developing Thai silk mask for use as an alternative to surgical mask.  In this research, SLRI researchers applied synchrotron light to analyze three-dimensional structure of Pak Thong Chai silk and later created the silk mask for use as alternative to surgical mask.  The result showed that the created silk mask was more than 80% efficient at PM 2.5 and 0.3 micron filtration capacity.  The mask was also better than masks made of other fibers using for droplet transmission prevention and it was durable.  The mask development not only helps solving shortage of surgical mask but also increases quality of natural fabric in the region and raises income of community enterprise in Nakhon Ratchasima.

Another innovation created by SLRI is the development of particle permeation test for surgical mask.  A high-speed camera was applied for the test to examine permeation of sneeze and cough droplets through the mask.  The camera can take photos at high frame rate of up to 1,300 frames per second.  In studying permeation of sneeze and cough droplets, the qualified rate is just 200 frames per second to examine droplet permeation through the mask and detect motion occurred during recording and the researchers can examine droplet permeation through surgical masks.  The result showed that the created silk mask was better than a surgical mask at preventing saliva droplet permeation.

Read more on the SLRI website

Thailand is planning to build its ‘second’ Synchrotron Light Source

Synchrotron light source is the national infrastructure in science and technology for its contribution of research analysis from downstream, midstream, to upstream levels. Being an effective tool for advanced research, synchrotron promotes research targeting industrial applications for product development and innovation.

Thailand’s synchrotron radiation facility, the 2nd generation synchrotron light source, generates electron beam energy at 1.2 GeV covering spectral range from infrared to low-energy X-Rays. With such energy, the capacity of industrial and medical research is restricted due to the necessity of wider research techniques requiring higher energy and intensity of light. To produce high-energy X-Rays, Thailand should be compelled to develop the 4th generation of synchrotron light source with 2.5 times higher electron energy and 100,000 times higher intensity. This improvement aim to enhance research framework and facility service of Thailand to the leading position in medical, industrial, material, agricultural, food, and commercial research, including application and basic research, as well as becoming one of the top leaders in science and technology of Asia Pacific continent.

>Read more on the website of the Synchrotron Light Research Institute

Image: Architectural model of Thailand’s future second Synchrotron Light Source

The British Ambassador to Thailand visited the Synchrotron Light Research Institute

On June 19, 2017, H.E. Brian Davidson, the British Ambassador to Thailand and diplomatic corps of British Embassy honorably visited Synchrotron Light Research Institute – SLRI during the visit to Nakhon Ratchasima and Khon Kaen province. Director of SLRI, Prof. Wng, Cmdr. Dr. Sarawut Sujitjorn navigated His Excellency for the facility tour to Siam Photon Laboratory. On this occasion, His Excellency has followed up the progress of the Newton Fund partnership between the UK and SLRI in order to support in synchrotron research and capacity development.

At the end of the visit, His Excellency has given the interview regarding the impression upon the visit to SLRI as well as the prospect of UK and SLRI partnership “What’s amazing is the way that SLRI developed the facility from what it was originally, to expand the ability to do research and innovation from this project that quite designed from the technical expertise that is here in terms of people working here. The fact that you’re able to offer use of facility not just to people in Thailand but to people in the region in the way that’s going to help develop the capacity, the technology, the research base of the whole of the ASEAN not just Thailand to use the facility. From the UK’s prospect, we are delighted to be part of the process through our newton Fund to be able to support some of the capacity building to allow SLRI in Thailand from Synchrotron project here to offer more into Thailand, into the region.”

>Read more on the SLRI webpage