前天 (8月12日)，期刊BioEssays刊登了一份由Sirotkin & Sirotkin (2020) 的文章，內容回顧了過去八年有關冠狀病毒的GoF研究，引述了幾篇在這八年間刊登的文章，對了解冠狀病毒的GoF研究發展有很大幫助。

所謂GoF研究，是指 Gain-of-Function Research，根據NCBI (2020) 的定義，任何涉及基因型及其表型改變的選擇過程就是一項GoF研究。(”any selection process involving alteration of genotypes and their resulting phenotypes is considered a type of Gain-of-Function (GoF) research”)。

Potential Risks and Benefits of Gain-of-Function Research Summary of a Workshop

Potential Risks and Benefits of Gain-of-Function Research
Summary of a Workshop

文章介紹，早在2013年，Ge et al. (2013) 已於自然期刊發表文章，提到團隊成功從野生蝙蝠中分離出冠狀病毒，為一種靶向ACE2受體的冠狀病毒基因組的GOF研究奠定了基礎，項目的部份資金來自EcoHealth Alliance。Aizenman (2020) 更加發現在過去幾年，研究人員從蝙蝠中已分離出多達400種的冠狀病毒。

在隨後的幾年，EcoHealth Alliance獲得了一項有關冠狀病毒的GoF項目的研究經費，項目名為「UNDERSTANDING THE RISK OF BAT CORONAVIRUS EMERGENCE」，研究時間為2014年6月1日至2019年5月31日，據引述該項目是利用以下技術“[spike]‐protein sequence data, infectious clone technology, in vitro and in vivo infection experiments and analysis of receptor binding”來處理蝙蝠冠狀病毒基因組 (NIH, 2014)。

至2015年，一篇由Menachery et al. (2015) 題為 ”A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence”的文章，成功利用反轉基因法 (reverse genetics system) 研製出一種嵌合病毒 SHC014：”a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone”，結果顯示它能更有效在人類氣道複製：”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”

這些研究對我們今天了解COVID-19的傳播有重要的參考價值。

參考

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