Opthalmologist Paul versus infectious disease heavyweight Fauci on reputed "gain of function" coronavirus research: who is right?

A "debate" between Paul and Fauci is all over conservative US media at the moment (FoxNews, Newsmax and so on). 

It concerns controversial research which was completed and published in 2017 that is alleged to cause gain of function "GOF" by bat viruses. This GOF jargon means using genetic experiments to confer new (novel) abilities to viruses being studied. The research results are reported here and summaries and exact citation are provided below. The stated purpose of the work is to better understand the risks to humans posed by natural, previously unstudied viruses.

This work was indirectly funded by the US NIAID. Before it was initiated it was vetted by ethics and safety oversight panels that Dr Fauci -- as part of his job as the boss at US NIAID -- is responsible for. The scrutiny of Dr Fauci is part of political investigation of whether Dr Fauci carried out his job properly.

A good update on the lab-leak assumption for for explaining COVID-19 origin bundled up in this politicised argument is here. COSMOS Magazine have an explainer here. Another discussion of the lab-link speculations is here

Over to you Professor Racaniello:

Author summary

Increasing evidence has been gathered to support the bat origin of SARS coronavirus (SARS-CoV) in the past decade. However, none of the currently known bat SARSr-CoVs is thought to be the direct ancestor of SARS-CoV. Herein, we report the identification of a diverse group of bat SARSr-CoVs in a single cave in Yunnan, China. Importantly, all of the building blocks of SARS-CoV genome, including the highly variable S gene, ORF8 and ORF3, could be found in the genomes of different SARSr-CoV strains from this single location. Based on the analysis of full-length genome sequences of the newly identified bat SARSr-CoVs, we speculate that the direct ancestor of SARS-CoV may have arisen from sequential recombination events between the precursors of these bat SARSr-CoVs prior to spillover to an intermediate host. In addition, we found bat SARSr-CoV strains with different S proteins that can all use the receptor of SARS-CoV in humans (ACE2) for cell entry, suggesting diverse SARSr-CoVs capable of direct transmission to humans are circulating in bats in this cave. Our current study therefore offers a clearer picture on the evolutionary origin of SARS-CoV and highlights the risk of future emergence of SARS-like diseases.

Abstract

A large number of SARS-related coronaviruses (SARSr-CoV) have been detected in horseshoe bats since 2005 in different areas of China. However, these bat SARSr-CoVs show sequence differences from SARS coronavirus (SARS-CoV) in different genes (S, ORF8, ORF3, etc) and are considered unlikely to represent the direct progenitor of SARS-CoV. Herein, we report the findings of our 5-year surveillance of SARSr-CoVs in a cave inhabited by multiple species of horseshoe bats in Yunnan Province, China. The full-length genomes of 11 newly discovered SARSr-CoV strains, together with our previous findings, reveals that the SARSr-CoVs circulating in this single location are highly diverse in the S gene, ORF3 and ORF8. Importantly, strains with high genetic similarity to SARS-CoV in the hypervariable N-terminal domain (NTD) and receptor-binding domain (RBD) of the S1 gene, the ORF3 and ORF8 region, respectively, were all discovered in this cave. In addition, we report the first discovery of bat SARSr-CoVs highly similar to human SARS-CoV in ORF3b and in the split ORF8a and 8b. Moreover, SARSr-CoV strains from this cave were more closely related to SARS-CoV in the non-structural protein genes ORF1a and 1b compared with those detected elsewhere. Recombination analysis shows evidence of frequent recombination events within the S gene and around the ORF8 between these SARSr-CoVs. We hypothesize that the direct progenitor of SARS-CoV may have originated after sequential recombination events between the precursors of these SARSr-CoVs. Cell entry studies demonstrated that three newly identified SARSr-CoVs with different S protein sequences are all able to use human ACE2 as the receptor, further exhibiting the close relationship between strains in this cave and SARS-CoV. This work provides new insights into the origin and evolution of SARS-CoV and highlights the necessity of preparedness for future emergence of SARS-like diseases.

Source: 
Zheng XS, Wang MN, Daszak P, Wang LF, Cui J, Shi ZL. Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. PLoS Pathog. 2017 Nov 30;13(11):e1006698. doi: 10.1371/journal.ppat.1006698. PMID: 29190287; PMCID: PMC5708621.

Another virologist (Stuart Neil)  has comments about this Paul-Fauci debate on Twitter:

I can understand why Dr Fauci was incensed during these hearings.

Post Script:

It's worth noting that evidence for a non-laboratory origin of the pandemic continues to grow.

See later post:

Tweet of the month by Michael Worobey about paper of theyear: illegal sales of plausible SARS-CoV2 intermediate hosts such as civets in wet markets of Wuhan 2017-19