Since the start of the year, a novel coronavirus ravaged the whole world, infecting more than 37 million people and killing over 1 million globally. The virus outbreak, which was declared a pandemic in March, has since spurred research and global efforts to treat and limit further spread of the virus. At the core of this groundwork is genomic medicine, a cutting-edge field that explores diseases and treatments using the genetic material, or genome, of biological material.
Genomic medicine has been central in the recent progress made in identifying the virus and in developing therapeutics against the infection. From the early stages of discovering and isolating the virus to mapping its spread, genomics has played a crucial role in helping researchers better understand this entirely new virus and how we can deal with it.
In this article, we explore some of these critical applications of genomic medicine in the fight against the coronavirus pandemic and how it could transform treatment and vaccine developments in the future.
Diagnostics and Disease Surveillance
In the early days of the outbreak in Wuhan, China, upon realizing that pneumonia patients were not responding to treatment, Chinese scientists analyzed the lung fluid samples from some of the patients using genomic sequencing and identified the novel virus. With advances in genomic sequencing tools such as Nanopore Next-generation sequencing (NGS) and QIAGEN’s CLC software, this took the researchers only two weeks. For context, identifying the SARS virus in 2003 took more than six months, when sequencing techniques only allowed scientists to sequence DNA fragments one at a time.
The prompt identification of the virus set the stage for the development of test methods, including the reverse transcription-polymerase chain reaction (RT-PCR). The RT-PCR test works by detecting the viral genome in a patient’s sample. This one achievement led several biotech companies to develop test kits and machines that leveraged the RT-PCR testing process.
Next-generation sequencing also drove surveillance efforts, enabling researchers to map the spread of the infection. Using these advanced genomic sequencing tools, researchers have been able to identify over 40,000 sequences of the SARS-CoV-2 genome to provide information on the origin and spread of the virus. These data have shown that the virus shares 96% similarities with the coronavirus found in bats, and about 79.6% similarities with the SARS virus.
Further, next-generation sequencing modalities have enabled scientists to determine the pathways of the virus in the body, including its various stops and binding receptors in the body, and how it manipulates human cells to replicate itself.
The Nevada Genomics Center at the University of Nevada, Reno, is expanding this groundwork, advancing research to learn how the virus affects different populations. The center aims to sequence hundreds of samples from COVID-19 patients in northern and southern Nevada and add the results to an international database.
This database helps provide a large store of information on the virus that could help researchers to assess the impact of the virus on different patient populations.
Prevention and Treatments
A cardinal application of genomic data is to develop precision treatments modeled based on unique host-disease interactions. As the pandemic began, genomic sequencing data accelerated global research into the behavior of the virus in different population groups and the biological factors that drive susceptibility among various patient groups, to develop personalized treatment and prevention strategies. This has led researchers to launched projects to develop gene-based treatments and vaccines that could revolutionize strategies to tackle future epidemics.
There are currently more than 550 different treatments under investigation for the potential treatment of the infection; however, only antiviral drug Remdesivir has been approved by the US Food and Drug Administration (FDA) under Emergency Use Authorization (EUA). Leaders in genomic medicine are applying genetic sequencing tools and leveraging the database of the virus genome to develop potential cures for the infection.
For instance, the San Antonio Partnership for Precision Therapeutics recently announced funding for three projects aimed at accelerating intervention for COVID-19. The projects will focus on how biological substances, such as proteins in the respiratory tract and the immune system, influence individual responses to the virus, and how researchers can utilize these data to develop therapeutics.
Cleveland Clinic also launched a genomic medicine project to identify genetic factors that drive susceptibility to the virus and use these to develop prevention and therapeutic strategies against the virus. Emory University researchers are also investigating an antiviral compound that works like Remdesivir, which inhibits viral replication.
Using data from genomic sequencing, IBM’s Summit supercomputer found 77 compounds that block the virus’ binding protein, from which hundreds of new antiviral treatments could be developed. Other treatment approaches under consideration include drugs that could interfere with the replication of the virus and manipulating the protein it binds to in the lungs.
Genomic tools are also being applied in vaccine development against the coronavirus. Many vaccination efforts against the coronavirus seek to induce immunity against the virus by injecting weakened/deactivated SARS-CoV-2 virus or only viral proteins, including its spike protein and genetic material. This conventional vaccination method is based on the fact that these structures can stimulate the body to develop antibodies to neutralize the virus.
However, how long these antibodies would last in the body and how effectively they can neutralize the virus and prevent infection is uncertain. Many researchers have also cited concerns about accidental viral infection after the vaccine injection.
Other researchers are looking to leverage advanced genomic technology to develop DNA- and RNA-based vaccines. These vaccines consist of the DNA sequences that code for the viral antigens. Once injected, the DNA or RNA enters into the human cells and modulates the host’s cells to produce the antigens. These gene-based vaccines have the advantage of being easier and safer to develop, store, and transport. They also do not have a risk of accidental viral infection.
Genomics and the Future
Genomic medicine has revolutionized disease diagnostics and treatments in the last decade, with over 400 gene therapies in US clinical trials for a range of diseases, including infectious diseases and chronic diseases. In the wake of the current pandemic, genomics has spurred collaborative efforts between governments, researchers, and medical institutions to swiftly understand how the SARS-CoV-2 virus causes disease and employ the data to develop effective treatments.
