Scientists, Maciej Boni and colleagues at Pensylvania State University’s Center for Infectious Disease Dynamics, published in Nature Microbiology that the new coronavirus appears to have existed unnoticed in bats for decades. (1) They reconstructed the virus’ most recent evolution.
Horseshoe bats (see featured image) are the most probable origin of the SARS-CoV-2. Tracing the virus’s lineage is crucial early in an outbreak because it can allow health authorities to separate people from the pathogen’s animal host, and later to help avert future health crises.
The researchers warned that other virus lineages in bats could also have the potential to spread to humans and cause pandemic. The findings highlight how “difficult it will be to identify viruses with potential to cause major human outbreaks before they emerge,” as Maciej Boni and colleagues wrote. The research team reconstructed the virus’s evolution by tracing its recombination history. They concluded that pangolins probably didn’t act as a host for the virus although the scaly mammals may have played a role in touching off the pandemic by simply transmitting it. One of the most important conclusion of this study was that identifying the origins of an emerging pathogen can be critical during the early stages of an outbreak, because it may allow for containment measures to be precisely targeted at a stage when the number of new infections per day is still low.
Role and impact of genome sequencing techniques in prevention of pandemic:
Early detection by using genomics was not possible during Southeast Asia’s initial outbreaks of avian influenza H5N1 (in years 1997 and 2003–2004) or of the first SARS outbreak (between 2002–2003). By 2009, however, several rapid genomic analysis had become a routine component of outbreak response.
The 2009 influenza pandemic and subsequent outbreaks of MERS-CoV (in 2012), H7N9 avian influenza (in 2013), Ebola virus (in 2014) and Zika virus (in 2015) were all met with rapid sequencing and genomic characterization. For the current pandemic, the ‘novel pathogen identification’ component of outbreak response delivered on its promise, with viral identification and rapid genomic analysis providing a genome sequence and confirmation, within weeks, that the December 2019 outbreak first detected in Wuhan, China was caused by a coronavirus (2).
Unfortunately, a response that would achieve containment was not possible. Given what was known about the origins of SARS, as well as identification of SARS-like viruses circulating in bats that had binding sites adapted to human receptors appropriate measures should have been in place for immediate control of outbreaks of novel coronaviruses. (3).
The key to successful surveillance is knowing which viruses to look for and prioritizing those that can readily infect humans (4).
The existing diversity and dynamic process of recombination amongst lineages in the bat reservoir demonstrate how difficult it will be to identify viruses with potential to cause major human outbreaks before they emerge. This underscores the need for a global network of real-time human disease surveillance systems, such as that which identified the unusual cluster of pneumonia in Wuhan in December 2019, with the capacity to rapidly deploy genomic tools and functional studies for pathogen identification and characterization.
Validated protocols for generating high-quality, full-length severe acute respiratory syndrome coronavirus 2 genomes from primary samples were described by virologist, Paden and colleagues. (5) One protocol of these virus genome analyses uses multiplex reverse transcription PCR (polymerase chain reaction), followed by MinION™ (Oxford Nanopore, Co.) or MiSeq™ sequencing (Illumina, Co.) see Figure 1; the other uses singleplex, nested reverse transcription PCR and traditional Sanger sequencing. These protocols enable sensitive virus sequencing in different laboratory environments.
Figure 1. Pictures of sequencers MiSeq™ (left) and Minion™ (right) used for coronavirus genome sequencing
For cyclodextrin researchers familiar with the development and utility genome sequencers of Minion™ or Gridion™ by Oxford Nanopore Technologies, Ltd these results on viral genome analysis may have special meanings. We remember that the basic discovery of the working principle of nanopore-based sequencing method was done in the early 1990-ies, by Professor Hagan Bayley and his team. In the early phase of development, Bayley used a cyclodextrin-filled alpha-hemolysin nanopore for construction of the prototype sequencing set up. (6)
- Boni, M.F., Lemey, P., Jiang, X. et al. Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic. Nat Microbiol (2020). https://doi.org/10.1038/s41564-020-0771-4 28 July 2020
- Novel Coronavirus (2019-nCoV) Situation Report 1, 21 January 2020 World Health Organization, 2020. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200121-sitrep-1-2019-ncov.pdf?sfvrsn=20a99c10_4
- Menachery, V., Yount, B., Debbink, K. et al. A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. Nat Med 21, 1508–1513 (2015). https://doi.org/10.1038/nm.3985
- Holmes, E. C., Rambaut, A. & Andersen, K. G. Pandemics: spend on surveillance, not prediction. Nature558, 180–182 2018. doi: 10.1038/d41586-018-05373-w
- Paden et al et al. Rapid, Sensitive, Full-Genome Sequencing of Severe Acute Respiratory Syndrome Coronavirus-2 Infect. Dis. 2020 Jul 1; 26, doi:10.3201/eid2610.201800
- Banerjee, A. et al. Molecular bases of cyclodextrin adapter interactions with engineered protein nanopores PNAS May 4, 2010 107 (18) 8165-8170; https://doi.org/10.1073/pnas.0914229107