How do we respond to emerging pathogens?

The 2019-nCoV coronavirus is only the latest threat in a perpetual assault that has included HIV, Lyme disease, Zika, SARS, MERS, and others

Learn how advances in technology have changed the global response to emerging diseases, as well as the ways in which synthetic oligonucleotide manufacturers can help researchers in their efforts to head off global pandemics.

What do I need to know about this trending virus story?

Can it be fatal?

Is it coming to my country, state, or city?

I’m feeling a little under the weather…can my doctor tell me if I’ve contracted the 2019-novel coronavirus, 2019-nCoV?

These and other questions are what drive interest in stories about new diseases.

Unfortunately, such questions, and the flurry of inquiries surrounding them, can also drive panic. It has long been the sphere of pathologists and microbiologists working at the US Centers for Disease Control and Prevention (CDC) and other rapid-response institutions to head off that panic. And since the dawn of epidemiology, researchers have employed one key weapon against panic: information. That information has historically been about the natural history of the disease organism, prevention and progression of the disease, and the visible hallmarks of both the organism and its manifestation in infected patients. Today, that information also includes the genomic sequence of the pathogens. This, of course, puts the manufacturers of custom nucleic acids at a critical node in the process of addressing emerging pathogen crises and, even now, IDT is engaged in providing new reagents to help answer questions and assemble key information.

In the case of the 2019-nCoV (for 2019 novel coronavirus; and more recently designated SARS-CoV-2 by the International Committee on Taxonomy of Viruses), some of the key information has come quickly, with full viral genome sequences from several patients being generated in the initial days of the outbreak [1]. An article from the Wuhan Institute of Virology, released late last week, points to its likely origin in bats and suggests its close relation to the SARS coronavirus. 2019-nCoV/SARS-CoV-2 shares nearly 80% sequence identity with SARS and appears to leverage the same cell surface receptor for entry into the host [2]. That receptor, called ACE2, is shared by humans, bats, and several other animal species with which humans cross paths [3].

First response

With any emerging disease, early responders begin to address the information deficit by answering a handful of key questions: Where did the pathogen originate? How does it spread? How can we identify an infection rapidly and with confidence? Only then can researchers determine how best to limit the spread of these diseases, devise treatments, and ultimately, even vaccinate against them.

One of the most important steps in fighting emerging pathogens is identifying infected patients. This can be complicated by pathogens with longer incubation times or symptoms that are not distinct from common, non-threatening infections. This appears to be a significant problem with 2019-nCoV/Covid-19 disease, with some estimates of asymptomatic incubation times extending to 14 days. Obviously, failure to identify and treat infected people increases the risk and rate of the disease spreading. Additionally, patient observation and treatment regimens based on false-positive assessments lead down blind alleys and result in waste of precious time and resources. Therefore, the establishment of diagnostic methods accounts for a large part of early research activity around potential pandemics. Fortunately, researchers have gained a lot of ground on the diagnostic front over the past few decades.

The evolution of diagnostic techniques

Early methods for confirmation of specific infections were culture-based, followed by morphological and/or immunological analysis of lab-grown plaques and colonies. Such assays could be quite accurate, but the incubation times worked in opposition to the urgency of the research. Also, lab culture isn’t possible with all pathogens. With the advent of PCR, it became possible to quickly confirm infections with much smaller samples, by detecting native genetic sequences of the attacking microorganisms. By the turn of this century, culture-independent methods for identifying microbial signatures were developed, with molecular methods such as PCR-based amplification, DNA hybridization, and full genome sequencing being among the most sensitive and precise methods available [4].

Today, improvements in sequencing technologies mean that the genomes of disease agents are available much earlier in epidemiological studies, so native genetic information used in the development of diagnostics can be leveraged almost immediately. Additionally, advances in custom nucleic acid synthesis allow rapid manufacturing and delivery of oligonucleotides both for use in the development of such tests and as standards in diagnostic kits that can be deployed in the field. Synthetic oligos have also lowered the barrier to creating synthetic proteins, which can then be used as safe reagents for vaccine research. Advances in gene synthesis mean that subunit vaccines can be developed quickly from one or a few antigen-presenting viral genes, circumventing the need for scientists to handle live and potentially dangerous pathogens and allowing vaccine development against viruses that cannot be propagated in current model organisms.

With the burgeoning global economy, increased transparency from the governments of countries where outbreaks occur becomes critically important to controlling these outbreaks and preventing new ones. Such cooperation hasn’t always prevailed, but the response to this recent outbreak has been buoyed by the transparency of Chinese researchers and their government, leading to many collaborative efforts, with new information coming at an unprecedented pace [5].

The role of commercial oligonucleotide synthesis

All of this means that manufacturers of synthetic DNA, like IDT, often find themselves involved very early in the process of addressing emerging diseases. Our recent history includes assisting in the development of field diagnostic tests for Ebola virus and providing reagents to advance disease modeling and detection of Zika virus. In the case of the Wuhan outbreak, IDT was quickly engaged by researchers with interests in both diagnostic assays and vaccine development. IDT has already shipped synthetic genes for use in the pursuit of coronavirus vaccines, as well as customized oligonucleotide probes and primers that will facilitate more sensitive and accurate detection of 2019-nCoV/SARS-CoV-2.

One potential problem with simultaneously manufacturing both long genomic sequences and probes used in their detection is contamination: if the facility manufacturing diagnostic kits is also creating substantial quantities of native viral sequences, such contamination could easily lead to false positives and other inaccuracies in detection reagents. IDT is uniquely positioned to avoid such concerns, due both to our GMP units and facilities dedicated to production of diagnostic oligos. This allows us to serve the need for vaccine-directed synthetic viral genes in one location, while confining the manufacturing of diagnostic reagents to another city entirely, or even another continent.

IDT takes its position on the front lines of fighting new diseases very seriously, and we've set up a dedicated page for orders of reagents to be used in 2019-nCoV/SARS-CoV-2 research. We take pride in being able to offer the highest quality reagents to the dedicated researchers who jump into the fray at the first sign of trouble. These researchers work tirelessly to head off critical threats to the world’s populations, and IDT is committed to providing them with the most accurate and effective reagents to aid their missions.

2019-nCoV/SARS-CoV-2 reagents now available

IDT has assays, using the CDC design, and controls for positive identification of 2019-nCoV/SARS-CoV-2.

These assays are priced to make them widely accessible and ship in just 1–2 business days.

Order now

References

  1. Williams S. (2020) Where coronaviruses come from. [Online] The Scientist. [Accessed 27 Jan 2020].
  2. Zhou P, Yang X. (2020) Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin. bioRxiv doi: 10.1101/2020.01.22.914952.
  3. Martina BE, Haagmans BL, et al. (2003). Virology: SARS virus infection of cats and ferrets. Nature, 425(6961):915.
  4. Váradi L, Luo JL, et al. (2017) Methods for the detection and identification of pathogenic bacteria: past, present, and future. Chem Soc Rev, 46:4818–4832.
  5. Johnson CY. (2020) Scientists are unraveling the Chinese coronavirus with unprecedented speed and openness. [Online] The Washington Post. [Accessed 27 Jan 2020].

Published Jan 28, 2020