Editorial in News: India’s Pioneer Scientific Work Towards the COVID-19 Vaccine

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by Kamal Pratap Singh, Managing Editor, Biotech Express
Corresponding author: kamal9871@gmail.com

In India, ‘Lockdown’ was imposed on March 21, 2020 but a team of scientists headed by Prof Shailendra Saxena from KGMU performed the best possible experiments in early January, as soon as World Health Organization published out first Disease Outbreak News on the new virus, with a cluster of cases of pneumonia in Wuhan, to know about the genetic and biochemical machinery and tried to get as much information as possible for the risk assessment and making a vaccine for prevention. In his pioneer original research paper from India, his team not only suggested to rename this virus as SARS-CoV-2 which later was done by WHO, but also reported its pandemic potential.

Prof Shailendra K Saxena, KGMU, and his team of researchers published an original research article which was sent to journal on 24 January 2020, it was further accepted on 21st February 2020 and published online eventually, much before Indian scientists started to see CoV pandemic around the world. This earliest study from India has been planned to determine the sequence variation, structural and antigenic divergence of S glycoprotein which aimed to provide help for the management of 2019-nCoV infection.

The various strains of viruses used for the experiment are Wuhan seafood market pneumonia virus isolate Wuhan-Hu-1 2019-nCoV (MN908947.3), Wuhan seafood market pneumonia virus isolate Wuhan-Hu-12019-nCoV (NC_045512.2), Bat SARS-like Coronavirus isolate bat-SL-CoVZXC21 (MG772934.1), Bat SARS-like coronavirus isolate Rs4084 (KY417144.1), SARS Coronavirus MA15 isolate d3om4 (JF292919.1), SARS Coronavirus civet007 (AY572034.1) and SARS Coronavirus GD03T0013 (AY525636.1), whereas Japanese encephalitis virus (AF075723.1) was considered as an outlier.

The steps they performed were as following:
● The team used sequences of spike glycoprotein of SARS-CoV-2 (2019-nCoV) and SARS Coronavirus (SARS-CoV) for the comparison using EMBOSS Needle pairwise sequence alignment tools.
● Analysis for antigenicity was performed by NetCTL 1.2 and validated by IEDB Analysis Resource server. This server predicts the peptide MHC class I binding; proteasomal C terminal cleavage and transporter associated with antigen processing (TAP) protein transport efficiency.
● For structural divergence determination, the protein homology modeling was performed by using by using the spike glycoprotein sequences of SARS-CoV-2 (2019-nCoV) and SARS-CoV using HHPred server. The generated models for S glycoproteins of SARS-CoV-2 (2019-nCoV) (PDBA) and SARS-CoV (PDBB) were based on cryo-EM structure of the SARS coronavirus spike glycoprotein (PDB ID 6ACC). The generated models were superimposed to determine the structural divergence using SuperPose Version 1.0, which calculates the protein superposition using a modified quaternion approach.
● The variation in glycosylation sites was predicted by NetNGlyc 1.0 and validated by N-GlyDE server.

We found that this research from India suggested for the first time that SARS-CoV-2 (2019-nCoV) is closely related to SARS-CoV, which has only 12.8% of difference with SARS-CoV in S protein and has 83.9% similarity in minimal receptor-binding domain with SARS-CoV.

In glycosylation sites they found that the SARS-CoV-2 (2019-nCoV) spike glycoprotein exhibits common glycosylation sites that were also present in SARS-CoV such as NITN, NGTI, NITN, NFSQ, NESL, NCTF and NNTV. Their data suggests that the 2019-nCoV may interact with host receptor using novel glycosylation sites that may affect the internalization process and associated pathogenesis.

In addition, antigenic site analysis proposes that great antigenic differences exist between both the viral strains, but some of the epitopes were found to be similar between both the S proteins. They have found that most of the CTL epitopes are novel from the SARS-CoV. However, six epitopes RISNCVADY, CVADYSVLY, RSFIEDLLF, RVDFCGKGY, MTSCCSCLK and VLKGVKLHY were found to be identical in both the spike glycoproteins. In spite of the variation in S protein amino acid composition, they found no significant difference in their structures.

Collectively, for the first time their results exhibited that the emergence of human SARS-CoV-2 (2019-nCoV) is closely related to predecessor SARS-CoV and provide the evidence that SARS-CoV-2 (2019-nCoV) uses various novel glycosylation sites as SARS-CoV does and may have a potential to become pandemic owing its antigenic discrepancy.

Further, demonstration of novel Cytotoxic T lymphocyte epitopes may impart opportunities for the development of peptide based vaccine for the prevention of SARS-CoV-2 (2019-nCoV).

In his research paper written in January 2020 he concluded that human SARS-CoV-2 (2019-nCoV) is closely related to predecessor SARS-CoV, consequently, it should be renamed as SARS-CoV-2 and owing its pandemic potential it should be declared as a public health emergency of international concern at the earliest.

The research news was very well covered by Nature Asia and many other reputed Journals.

The Altmetric available on Springer article shows that the article has been accessed more than 14,000 times. Altmetric has tracked 14,991,487 research outputs across all sources so far and compared to these this one has done particularly well and is in the 94th percentile: it is in the top 10% of all research outputs ever tracked by Altmetric. Even a recent science show (Why Is SARS-CoV-2 So Contagious?) from USA, on SARS-CoV-2 (2019-nCoV) vs SARS-CoV, is based on this original research paper.

References
1. Kumar, S., Maurya, V.K., Prasad, A.K. et al. Structural, glycosylation and antigenic variation between 2019 novel coronavirus (2019-nCoV) and SARS coronavirus (SARS-CoV). VirusDis. 31, 13–21 (2020). https://doi.org/10.1007/s13337-020-00571-5
2. Study uncovers routes to vaccine for novel coronavirus. doi:10.1038/nindia.2020.52 Published online 28 March 2020
3. https://www.altmetric.com/details/77179273#score

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