Comparative genomics of SARS-CoV2 and Rubella virus

Dr. Rahul Remanan,
CEO, Moad Computer

“If it could be demonstrated that any complex organ existed, which could not possibly have been formed by numerous, successive, slight modifications, my theory would absolutely break down. But I can find no such case.”
  -- Charles Darwin, The Origin of Species​

The SARS-CoV2 virus is the pathogen responsible for the COVID19 pandemic. Even though the SARS-CoV2 virus is a new pathogen, its origin follows the principles of evolution. Therefore, it is very likely that the SARS-CoV2 virus will have genomic similarities with other viruses. I became fascinated by the possible genomic similarities of the SARS-CoV2 virus with other viruses, especially with the Measles, Mumps Rubella (MMR) group of viruses.  My focus on this particular group of viruses was due to the recent news that the MMR vaccine could be also effective against the SARS-CoV2.¹ My reasoning for the MMR vaccine to work against SARS-CoV2 being the shared genomic similarities between these viruses. These genomic similarities could have contributed to the shared immuno-physiological profiles, thus causing the MMR vaccine to be effective against SARS-CoV2.

To verify this hypothesis, the first step was to identify any genomic similarities between the MMR group of viruses and the SARS-CoV2 virus. Therefore, I decided to run a simple genomic comparison experiment. I picked the Rubella virus first because, both the SARS-CoV2 and the Rubella are positive sense, single stranded RNA viruses, that are respiratory transmitted. I wanted to see if there were more fundamental genomic similarities between the two. 

I obtained the genetic information for both SARS-CoV2² and Rubella³ from the publicly available National Library of Medicine Nuccore database. I used an in-house end-to-end automated genome analysis pipeline developed using Python3 programming language to perform the global genomic alignments. The initial results demonstrated that the largest contiguous region of overlap was 608 nucleotides long, in the ​orf1ab gene of SARS-CoV2. Correspondingly the longest contiguous overlap of nucleotides in the Rubella genome portion was 4 nucleotides long. There was a 27.80% similarity in the nucleotide sequences of this region. The average similarity in the  nucleotide sequences of the SARS-CoV2 and the Rubella was 34.79%.

The global genome alignment was followed-up using an exact sequence matching experiment. The goal of the sequence matching was to identify the longest common nucleotide sequences between the SARS-CoV2 virus genome and the Rubella virus genome. This process identified a 14 nucleotide long  sequence common to both the SARS-CoV2 genome and the Rubella genome. In the SARS-CoV2 genome, this longest common nucleotide sequence was located in the gene coding for the ORF8 protein. Correspondingly, in the Rubella virus genome,  this sequence was present in the gene coding for the capsid protein. 

Similar comparative genomics studies of the SARS-CoV2 virus with the MMR group of viruses have also demonstrated the existence of genomic homology with the Rubella virus.⁴ I am working on extending our analysis to compare the SARS-CoV2 genetic structure with the Measles and the Mumps viruses. The genetic similarities between the MMR group of viruses and the SARS-CoV2 virus therefore show a great promise as to why MMR vaccine could be a powerful tool to control the spread of SARS-CoV2 and bring an end to the COVID19 pandemic.

References:
1. Analysis of Measles-Mumps-Rubella (MMR) Titers of Recovered COVID-19 Patients
Jeffrey E. Gold, William H. Baumgartl, Ramazan A. Okyay, Warren E. Licht, Paul L. Fidel Jr., Mairi C. Noverr, Larry P. Tilley, David J. Hurley, Balázs Rada, John W. Ashford
mBio Nov 2020, 11 (6) e02628-20; DOI: 10.1128/mBio.02628-20 
2. Complete genome sequences of Rubella virus genotype 2B isolates from South Korea in 2015
Kang,H.J., Kim,Y.-J., Lee,H.M., Nam,J.-G. and Kim,S.S.
3.  The first 2019 novel coronavirus case in Nepal
Bastola,A., Sah,R., Rodriguez-Morales,A.J., Lal,B.K., Jha,R., Ojha,H.C., Shrestha,B., Chu,D.K.W., Poon,L.L.M., Costello,A., Morita,K. and Pandey,B.D.
Lancet Infect Dis (2020), Vol 20, Issue 3, P279-280, March 01, 2020; DOI: 10.1016/S1473-3099(20)30067-0
4. Homologous protein domains in SARS-CoV-2 and measles, mumps and rubella viruses: preliminary evidence that MMR vaccine might provide protection against COVID-19
Robin Franklin, Adam Young, Bjoern Neumann, Rocio Fernandez, Alexis Joannides, Amir Reyahi, Yorgo Modis
medRxiv 2020.04.10.20053207; doi: https://doi.org/10.1101/2020.04.10.20053207