On August 12, an article by Sirotkin & Sirotkin (2020) published in the journal BioEssays reviews the GoF research on coronaviruses, citing several important articles published in the past eight years. It is very helpful to understand the development of GoF research on coronavirus.
GoF research means Gain-of-Function Research. According to the definition of NCBI (2020), “any selection process involving alteration of genotypes and their resulting phenotypes is considered a type of Gain-of-Function (GoF) research”.
The article says, as early as in 2013, Ge et al. (2013) publish an article in the journal Nature, mentioning that “a coronavirus that targets the ACE2 receptor like SARS‐CoV‐2 was first isolated from a wild bat in 2013… This research was funded in part by EcoHealth Alliance and set the stage for the manipulation of bat‐borne coronavirus genomes that target this receptor and can become airborne.”
Aizenman (2020) further discovered that in the past few years, researchers have isolated up to 400 types of coronaviruses from bats.
And in subsequent years, EcoHealth Alliance received funding for a project which is titled “UNDERSTANDING THE RISK OF BAT CORONAVIRUS EMERGENCE”. The research period is from June 1, 2014 to May 31, 2019. It outlines the gain‐of‐function research to be done, hoping to use cell cultures and humanized mice as well as “[spike]‐protein sequence data, infectious clone technology, in vitro and in vivo infection experiments and analysis of receptor binding” NIH (2014).
By 2015, an article entitled “A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence” by Menachery et al. (2015) says they successfully developed “a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone” by using reverse genetics system. “The results indicate that group 2b viruses encoding the SHC014 spike in a wild-type backbone can efficiently use multiple orthologs of the SARS receptor human angiotensin converting enzyme II (ACE2), replicate efficiently in primary human airway cells and achieve in vitro titers equivalent to epidemic strains of SARS-CoV”
These studies have important reference value for our understanding of the spread of COVID-19 today.
Aizenman, N. (2020) New Research: Bats Harbor Hundreds Of Coronaviruses, And Spillovers Aren’t Rare, Feb 20. https://www.npr.org/sections/goatsandsoda/2020/02/20/807742861/new-research-bats-harbor-hundreds-of-coronaviruses-and-spillovers-arent-rare
Ge, X., Li, J., Yang, X., A.A. Chmura, G. Zhu, J. H. Epstein, J. K. Mazet, B. Hu, W. Zhang, C. Peng, Y. J. Zhang, C. M. Luo, B. Tan, N. Wang, Y. Zhu, G. Crameri, S. Y. Zhang, L. F. Wang, P. Daszak, Z. L. Shi (2013) Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor, Nature 503, 535–538. https://doi.org/10.1038/nature12711
Menachery, V.D., Yount, B.L., Jr.,K. Debbink, S. Agnihothram, L. E. Gralinski, J. A. Plante, R. L. Graham, T. Scobey, X. Y. Ge, E. F. Donaldson, S. H. Randell, A. Lanzavecchia, W. A. Marasco, Z. L. Shi, R. S. Baric (2015) A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence, Nat. Med. 21, 1508
NCBI (2020) Potential Risks and Benefits of Gain-of-Function Research: Summary of a Workshop, NCBI. https://www.ncbi.nlm.nih.gov/books/NBK285579/
NIH (2014) Understanding the Risk of Bat Coronavirus Emergence, National Institutes of Health, U.S. Department of Health and Human Services. projectreporter.nih.gov/project_info_description.cfm?aid=8674931&icde=49750546
Sirotkin, K. & Sirotkin, D. (2020) Might SARS‐CoV‐2 Have Arisen via Serial Passage through an Animal Host or Cell Culture? BioEssays, https://doi.org/10.1002/bies.202000091