Tuesday, July 27, 2021

Rand Paul, M.D., United States Senator: ‘I write to urge the United States Department of Justice to open an investigation into testimony made to the United States Senate Committee on Health, Education, Labor, and Pensions by Dr. Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases (NIAID), on May 11, 2021…Under 18 U.S.C § 1001, whoever "makes any materially false, fictitious, or fraudulent statement or representation" as part of"any investigation or review, conducted pursuant to the authority of any committee, subcommittee, commission or office of the Congress, consistent with applicable rules of the House or Senate" is subject to criminal fines and imprisonment of up to five years. I ask that you investigate whether Dr. Fauci's statements to Congress on May 11, 2021 violated that statute or any other.’

 

https://drive.google.com/file/d/1WC1dYgVn2VNkcMsfip0X2FxsJ8CLu--L/view?usp=sharing 
RAND PAUL
United States Senate
WASHINGTON, DC 20510
July 21, 2021
The Honorable Merrick Garland
Attorney General
U.S. Department of Justice
Washington, DC 20530

A Report of the National Science Advisory Board for Biosecurity
May 2016
RECOMMENDATIONS FOR THE EVALUATION AND OVERSIGHT OF PROPOSED GAIN-OF-FUNCTION RESEARCH

Box 1. Gain-of-Function Research

 Recently, the phrase “gain-of-function research” has become synonymous with certain studies that enhance the ability of pathogens to cause disease. However, gain-of-function studies, as well as loss-of-function studies, are common in molecular microbiology and are essential to understanding molecular pathogenesis of infectious diseases. Changes to the genome of an organism, whether naturally occurring or directed through experimental manipulations in the laboratory, can result in altered phenotypes, as biological functions are lost or gained. Investigators routinely conduct loss- and gain-of-function experiments to understand the complex nature of host-pathogen interactions that underlie transmission, infection, and pathogenesis.

The term “gain-of-function” is generally used to refer to changes resulting in the acquisition of new, or an enhancement of existing, biological phenotypes. This report further defines “gain-of-function research of concern” to describe the subset of studies that have been the subject of recent debate and have raised potential biosafety and biosecurity implications. These are gain-of-function studies with the potential to generate pathogens with pandemic potential in humans by exhibiting high transmissibility and high virulence. See Section 6 for a more rigorous description of GOF research of concern (GOFROC).


Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus
Ben Hu , Lei-Ping Zeng , Xing-Lou Yang , Xing-Yi Ge, Wei Zhang, Bei Li, Jia-Zheng Xie, Xu-Rui Shen, Yun-Zhi Zhang, Ning Wang, Dong-Sheng Luo, Xiao-Shuang Zheng, Mei-Niang Wang, Peter Daszak, Lin-Fa Wang, Jie Cui , Zheng-Li Shi
Published: November 30, 2017 https://doi.org/10.1371/journal.ppat.1006698

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


Construction of recombinant viruses


Recombinant viruses with the S gene of the novel bat SARSr-CoVs and the backbone of the infectious clone of SARSr-CoV WIV1 were constructed using the reverse genetic system described previously [23] (S9 Fig). The fragments E and F were re-amplified with primer pairs (FE, 5’-AGGGCCCACCTGGCACTGGTAAGAGTCATTTTGC-3’, R-EsBsaI, 5’-ACTGGTCTCTTCGTTTAGTTATTAACTAAAATATCACTAGACACC-3’) and (F-FsBsaI, 5’-TGAGGTCTCCGAACTTATGGATTTGTTTATGAG-3’, RF, 5’-AGGTAGGCCTCTAGGGCAGCTAAC-3’), respectively. The products were named as fragment Es and Fs, which leave the spike gene coding region as an independent fragment. BsaI sites (5’-GGTCTCN|NNNN-3’) were introduced into the 3’ terminal of the Es fragment and the 5’ terminal of the Fs fragment, respectively. The spike sequence of Rs4231 was amplified with the primer pair (F-Rs4231-BsmBI, 5’-AGTCGTCTCAACGAACATGTTTATTTTCTTATTCTTTCTCACTCTCAC-3’ and R-Rs4231-BsmBI, 5’-TCACGTCTCAGTTCGTTTATGTGTAATGTAATTTGACACCCTTG-3’). The S gene sequence of Rs7327 was amplified with primer pair (F-Rs7327-BsaI, 5’-AGTGGTCTCAACGAACATGAAATTGTTAGTTTTAGTTTTTGCTAC-3’ and R-Rs7327-BsaI, 5’- TCAGGTCTCAGTTCGTTTATGTGTAATGTAATTTAACACCCTTG-3’). The fragment Es and Fs were both digested with BglI (NEB) and BsaI (NEB). The Rs4231 S gene was digested with BsmBI. The Rs7327 S gene was digested with BsaI. The other fragments and bacterial artificial chromosome (BAC) were prepared as described previously. Then the two prepared spike DNA fragments were separately inserted into BAC with Es, Fs and other fragments. The correct infectious BAC clones were screened. The chimeric viruses were rescued as described previously [23].

Funding: This work was jointly funded by National Natural Science Foundation of China (81290341, 31621061) to ZLS, China Mega-Project for Infectious Disease (2014ZX10004001-003) to ZLS, Scientific and technological basis special project (2013FY113500) to YZZ and ZLS from the Ministry of Science and Technology of China, the Strategic Priority Research Program of the Chinese Academy of Sciences (XDPB0301) to ZLS, the National Institutes of Health (NIAID R01AI110964), the USAID Emerging Pandemic Threats (EPT) PREDICT program to PD and ZLS, CAS Pioneer Hundred Talents Program to JC, NRF-CRP grant (NRF-CRP10-2012-05) to LFW and WIV “One-Three-Five” Strategic Program (WIV-135-TP1) to JC and ZLS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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