News

The SARS-CoV-2 virus is a submicroscopic organism with little spikes (S-protein) jetting out of its surface and viral genome inside it. The virus uses its S-protein to attach to a human host cell surface protein called ACE2, that usually plays a role in the maintenance of blood pressure, and sneaks into the cell. Once inside the cell, the virus takes control of the cellular machinery to make copies of itself and eventually gets out to infect other neighboring cells.

Highlights of the publication

• Natural variants in the gene encoding ACE2 surface protein were identified in different human population.
• Identification of the variations in ACE2 located in positions that are key for the virus S-protein interaction.
• Mutations in ACE2 surface protein enhances or reduces the interaction between viral S protein and the ACE2 protein.
• Based on ACE2 mutations, susceptibility or resistance to COVID19 infections can be predicted.
• This work will enable clinical studies that can correlate clinical symptoms with the reported ACE2 variation types.

For more details, please read the scientific paper https://www.biorxiv.org/content/10.1101/2020.04.07.024752v1

In an article featured on the cover of the January 2020 issue of Nature Genetics, scientists from SciGenom Research Foundation (SGRF), India, AgriGenome Labs, India, MedGenome, India/USA, SciGenom, India, and Genentech, a member of the Roche group, along with a team of international collaborators from academia and industry report the sequencing and assembly of a high-quality genome of the highly venomous, medically important Indian cobra (Naja naja). Using a combination of cutting-edge genomic technologies, the authors have assembled the most contiguous genome of this iconic venomous snake.

Venom is a complex mixture of proteins encoded by genes that have been co-opted by some snakes as they evolved some 100 million years ago. In the Indian cobra genome, the authors identified 19 key toxin genes primarily expressed in the venom glands.

"Targeting these 19 specific toxins using synthetic human antibodies should lead to a safe and effective antivenom for treating Indian cobra bites" said Dr. Sekar Seshagiri, President, SGRF, former Staff Scientist at Genentech, and lead study author. Currently, antivenom is produced by immunizing horses with extracted snake venom and is based on a process developed well over 100 years ago. This process is laborious and suffers from a lack of consistency leading to varying efficacy and serious side effects.

"It is about time we modernize antivenom development by leveraging genomics, recombinant protein expression and synthetic antibody development technologies. The Indian cobra genome and the catalogue of target toxins are a blueprint needed to do this. For the first time, we now have a full list of venom-relevant toxin genes of the Indian cobra" said Dr. R. Manjunatha Kini, Professor, National University of Singapore (NUS), Singapore and an author on the study.

Venom is primarily used by snakes to subdue their prey. It is also a great source of drug-like molecules. The Indian cobra genome is no exception and it codes for toxin molecules that can block pain, reduce blood pressure and prevent blood clotting.

Snakebite crisis

Globally each year, accidental contact with snakes lead to over 100,000 deaths. Over 400,000 individuals suffer permanent disabilities, including amputation. India alone accounts for 2.8 million snakebite cases that lead to about 50,000 deaths annually, primarily attributed to the Indian cobra, common krait, Russell's viper and saw scaled viper, infamously called the 'big four'.

"The Indian cobra is the first of the 'big four' deadly snakes to be sequenced. This is a major step towards understanding its venom components and it will effectively change the way antivenom is developed" said Dr. George Thomas, Chief Operating Officer, AgriGenome Labs, India. He further added, "This study has provided a very high-quality reference genome that will make assessment of the Indian cobra genetic diversity possible and practical. It will be an important resource for conservation of this revered and feared Indian snake".

"Obtaining the genomes and the venom gland genes from the other three of the ‘big four’ and the deadly African snakes such as the black mamba, carpet viper and spitting cobras is the logical next step. It will provide a complete platform for developing a safe, universal antivenom for snakebite victims all over India, Africa and other neighbouring countries" added Dr. R. Manjunatha Kini.

Safe and effective antivenom is a major unmet social need in India and other parts of the world. The world health organization (WHO) has classified snakebite as a neglected tropical disease (NTD). Institutions such as the Welcome Trust have announced funding for development of better antivenom. The Dept. of Biotechnology, under the Ministry of Science and Technology, Govt. of India, has also announced funding opportunities for antivenom development in India. These developments along with the insights gained from genome sequencing as reported in Nature Genetics, will help develop better antivenom that can end the snakebite crisis.

Media contact:
Ms. Kamalika Das
Tel: +91-8374274074
Email: info@sgrf.org

About SGRF

SciGenom Research Foundation (SGRF), a not-for-profit organization, is working to promote Science in India through research and education. Currently, the foundation is involved in a number of research initiatives that are typically not funded by government agencies, but identified as scientifically relevant and important for India. SGRF has ongoing research activities and collaborations in agriculture, animal health, wildlife diseases, biodiversity, genomics and human health. As part of its educational initiative, it organizes the annual Nextgen Genomics, Biology, Bioinformatics and Technologies (NGBT) Conference. The 10th international NGBT will be held in Kolkata, India from Sep 27th to Sep 30th, 2020.

About AgriGenome Labs

AgriGenome Labs is the leading genomics service provider in India offering high-quality genome sequencing and bioinformatics analysis for the research and breeding community of the country. AgriGenome’s services cover non-human organisms including plants, animals, fungi, bacteria and viruses. The in-house genome sequencing group has expertise in genome assembly and annotation. AgriGenome's R&D activities focus on crop improvement through TILLING and CRISPR-Cas9 based genome editing. Furthermore, AgriGenome Labs has completed genomes of several Indian spices, medicinal plants and livestock - some under its own R&D program and the rest in collaboration with other groups.

About MedGenome

MedGenome is a global leader in personalized medicine with unique genomic solutions in immuno-oncology, ophthalmology and other rare diseases. It has a high-throughput NGS facility in Foster City, California, supporting biomarker identification and target discovery research projects for bio-pharma and academic institutions in the US, Europe and Canada. It is a market leader in genetic diagnostic testing in India. MedGenome has developed algorithms and tools to correlate genomic data with clinical and phenotypic information to provide deep insight into complex diseases at genetic and molecular level to enable support drug development and personalized medicine.

About SciGenom

SciGenom is an ISO certified company, with a fully functional state-of-the-art molecular biology laboratory in Cochin. Its R&D lab is recognized by Department of Scientific & Industrial Research (DSIR), Ministry of Science & Technology, Government of India. SciGenom currently provides DNA cloning, protein expression and assay development services to both national and international clients. It also has antibody development capabilities for both diagnostic and therapeutic applications. SciGenom Labs also serves as a sandbox for life sciences startup ideas and has successfully incubated several companies.

Journal reference

Nature Genetics, Jan 6th, 2020 - https://www.nature.com/articles/s41588-019-0559-8