Advances in genomics research increased the speed with which vaccines came to the fore to mitigate infection by the SARS-CoV-2 virus, thanks to early sequencing of the virus. Here is a quick roundup of some recent genomics news related to COVID-19.
Synthetic genomes for emerging variants
San Diego-based Codex DNA Inc., announced in March that they released the world’s first full-length synthetic genomes for two emerging variants of the SARS-CoV-2 virus.
The new genomes include the B.1.1.7 variant that initially emerged in the United Kingdom and the B.1351 variant that was first detected in South Africa. These genomes were synthesized and constructed de novo using Codex DNA’s BioXp 3250 system.
“These ‘off-the-shelf’ SARS-CoV-2 synthetic genome variants will drive the development of vaccines, therapeutics, and diagnostics for COVID-19 research. Unlike controls released by other companies, our synthetic genomes do not need additional processing steps, thus reducing time, cost, and labor that can be better focused in other parts of the discovery and development process.” said Todd Nelson, CEO of Codex DNA. “We believe these new tools will be key resources in the ongoing fight against COVID-19 and we are pleased to be able to deliver them so quickly to the scientific community.”
Synthetic genomes enable researchers to rapidly and safely perform their discovery and development efforts for SARS-CoV-2 and to develop breakthrough therapies and diagnostics for the virus. They can also reduce or eliminate the costs and complexity of highly regulated biosecurity facilities required for studying the dangerous pathogen. As new variants spread, it is essential for researchers to rapidly design, build, and test their genomes to ensure that future experimental outcomes are directly applicable to their goals.
Together with previously released genomes, Codex DNA now offers 12 SARS-CoV-2 synthetic genomes. These new variant genomes can be activated easily using established in-vitro methods for use in developing or testing monoclonal antibody therapies or vaccines. These genomes can also serve as diagnostic controls specific to the UK and South Africa variants.
Sequencing to support SARS-CoV-2 testing
Also in March, Birmingham, UK-based Nonacus—a provider of genetic testing products for precision medicine and liquid biopsy—announced the commercial launch of a new service for whole-genome sequencing of SARS-CoV-2, developed to enable the UK government’s Test-To-Release scheme. Assay development for the new service was funded by a grant from Innovate UK.
During the pandemic, Nonacus expanded its accredited service facility to support a complete SARS-CoV-2 testing workflow and developed the new rapid whole-genome viral sequencing library approach with nanopore sequencing.
According to Chris Sale, CEO of Nonacus, a faster, lower-cost offering like this will be key in identifying and monitoring variants.
Indentifying host factors that lead to infection
Researchers at Belgian university KU Leuven recently described genetic screens of SARS-CoV-2 and human coronavirus (HCoV) 229E (one of the viruses that causes the common cold) in a paper published in Nature Genetics.
The team discovered that SARS-CoV-2 requires the lysosomal protein TMEM106B to infect human cell lines and primary lung cells. Overexpressing TMEM106B enhanced SARS-CoV-2 infection, suggesting that it plays a role in viral entry. After doing single-cell RNA-sequencing of airway cells from patients with COVID-19, they also uncovered that TMEM106B expression correlated with SARS-CoV-2 infection.
In addition, scRNA-seq analysis of airway cells from COVID-19 patients showed higher TMEM106B expression levels in infected individuals compared to infection-free patients. This may mean that high TMEM106B expression increases the susceptibility to SARS-CoV-2 and contributes to faster spread of COVID-19. The researchers suspect that TMEM106B may be used as a prognostic biomarker for disease severity of COVID-19 in patients, but further investigation is necessary to explore this idea.
Are we looking at an endemic now?
GlobalData reports that the SARS-CoV-2 virus variant first identified in South Africa underscores a critical weakness in combating the pandemic; it may prolong the presence of the disease indefinitely.
In part, GlobalData’s warning note came on the heels of South Africa announcing that it was going to suspend use of AstraZeneca’s COVID-19 vaccine (AZD1222) because the efficacy was below 25 percent in that country. This news came on the same day a World Health Organization panel met to recommend its use, citing 63-percent efficacy overall.
“AstraZeneca’s reduced efficacy in South Africa may reflect that over 90 percent of cases in South Africa are the B.1.351 variant, which suggests that the South African variant can effectively evade neutralizing antibodies produced by the AZD1222 vaccine,” said Walter Gabriel, an epidemiologist at GlobalData. “While other vaccines may be effective against this strain, it does not exclude the possibility that such efficacy may not be the case for future strains.”
As GlobalData noted, it may take years for most of the world’s population to get vaccinated, making future mutations more likely. This could prolong the epidemic into an endemic (much like we see with seasonal influenza) as herd immunity will be difficult, if not impossible, to reach without properly working vaccines.