ESC - a compendium of genetic variants in SARS-CoV-2 associated with immune escape

Mercy Rophina
04 January 2020

The SARS-CoV-2 virus being an RNA virus has a modest and almost constant rate of genetic variation. This roughly translates to approximately 3-4 per month. Ever since the onset of the COVID-19 pandemic in 2019 from the seafood market in Wuhan, China, there has been immense scientific interest in monitoring the variations in global genome sequences and also in exploring and understanding the origin, evolution and spread of the virus. Characterization of genetic variations accumulated in the pathogen can provide valuable insights on the mechanisms of pathogenesis, infectivity and immune response.


The pandemic also saw a significant and unprecedented application of genomic tools to understand the genetic epidemiology of SARS-CoV-2 as it spread across the world. As a result, a huge amount of genomic data has been made available constantly on public domain resources. Currently more than 3,00,000 genomes of global SARS-CoV-2 isolates are available in public domain resources across the world. This has also resulted in a number of resources that systematically compile genome and genetic variant information of SARS-CoV-2.


Are all variations significant ?

While all viruses have a tendency to mutate naturally and thereby accumulate genetic changes in their genome, in many cases, these mutations are usually chance events which might or might not confer significant impact on the viral properties.


D614G variant in the Spike protein of SARS-CoV-2 is one of the earliest and predominant examples of a genetic variant reported to be associated with increased infectivity. Variants impacting protein stability, infectivity, transmissibility and immune evasion are constantly being reported in literature with experimental evidence. This urges the need to systematically evaluate the functional role of variations for effectively combating the pandemic.


Presently, over 450 SARS-CoV-2 variations with explicit functional consequences spanning the structural and non-structural proteins of the pathogen are known and compiled by the FAVICOV resource maintained at CSIR Institute of Genomics and Integrative Biology. FAVICOV is one of the only public resources providing a catalog of functional variation in SARS-CoV-2 from various literature sources.



Escape mutations and their roles in Immune evasion

Antibody response to SARS-CoV-2 is one of the key immune responses to SARS-CoV-2 which is actively being used for surveillance (Antibody tests) as well as being actively pursued to develop therapeutic strategies and vaccines. Targeting of spike protein domains by broad-neutralizing antibodies would serve as an effective means of treating and preventing further infections of COVID-19. Incidentally many of the vaccine candidates also aim at developing neutralising antibodies targeting the spike protein. A number of recent publications have explored the potential of SARS-CoV-2 to evade specific antibodies as well as panels of convalescent plasma by virtue of specific genetic variants.


With numerous public resources cataloguing genome sequences and genetic variations there has been a paucity of resources systematically collecting and evaluating evidence on the immune escape variants. An explicit compilation of SARS-CoV-2 variants with potential immune escape properties would significantly enhance the scientific interventions.


To this end, we have been compiling a comprehensive catalog of genetic variants in SARS-CoV-2 associated with immune escape. This compendium is available as a searchable web interface and currently catalogues a total of 467 entries accounting for 129 unique variants evaluated against 74 antibodies. This resource enables the user to gain access to extensive computationally predicted functional annotation of the variants which we hope would contribute in exploring and understanding the underlying mechanisms of immune response against the pathogen.


The web interface to the resource is available at http://clingen.igib.res.in/esc/. Since the field is evolving, we look forward to having frequent updates as evidence emerges across the world. 

How does this resource help ?

In our belief, this resource would be central to understanding the biology of immune escape in SARS-CoV-2 and therefore our ability to develop better vaccines in the future. It has also not escaped our mind that emergence of immune escape could point to specific immune restraints placed by immunological therapies - including convalescent plasma, antibodies or vaccines as they are being rolled out across different countries.


Related Resources


IndiCoV - Resource for Indian CoV-2 Genomes and Variants. Accessible at http://clingen.igib.res.in/indicov/


FaviCoV - Functional Annotation of Genetic Variants in SARS-CoV-2. Accessible at https://clingen.igib.res.in/favicov/

Mercy Rophina is a graduate student at CSIR-IGIB. All opinions expressed are personal and do not reflect the opinion of their employers or organisations associated. The Author can be reached at @mercy_rophina on Twitter