>>8671374

nice post anon

` With $500M spent by Army training for underground ops ( https://www.military.com/daily-news/2018/06/24/army-spending-half-billion-train-troops-fight-underground.html )

` and a redonkulous number of ventilators ( for them? and COVID the cover )

` it sure feels like WWIII already commenced beneath our feet…

` Gotthard BASE Tunnel had an overly Luciferian ceremony FOR the world leaders ~9/25/2016 months before Trump took the riegns.

( 6 hrs of footage, but cued to some bizarre stuff: https://youtu.be/I4NU0Tok1T4 )

` And "It lies at the heart of the Gotthard axis and constitutes the third tunnel connecting the cantons of Uri and Ticino, after the Gotthard Tunnel and the Gotthard Road Tunnel."

` "The Gotthard Base'' Tunnel, with a length of 57.09 kilometres (35.47 mi) and a total of 151.84 km (94.3 mi) of tunnels, shafts and passages, is the longest railway tunnel in the world,[note 2] with a geodetic distance of '55.782 kilometres (34.661 mi) between the two portals.[4][9"

` It is the deepest railway tunnel in the world, with a maximum depth of 2,450 metres (8,040 ft),[4] comparable to that of the deepest mines on Earth. Without ventilation, the temperature inside the mountain reaches 46 °C (115 °F).[4] ← ~1.5mi

=sounds like there's smaller terrestial countries=

( https://en.wikipedia.org/wiki/Gotthard_Base_Tunnel )

` The Richest & Most Powerful have spent several GDPs on the project.

` CERN is also the size of a city, but will leave it here…

` almost

` Eight experiments (CMS, ATLAS, LHCb, MoEDAL,[25] TOTEM, LHCf, FASER and ALICE)

` And a possible Cypher for the elusive 'ATLAS' riddle:

` "The SPS and LEP/LHC tunnels are almost entirely outside the main site, and are mostly buried under French farmland and invisible from the surface. However, they have surface sites at various points around them, either as the location of buildings associated with experiments or other facilities needed to operate the colliders such as cryogenic plants and access shafts. The experiments are located at the same underground level as the tunnels at these sites."

` "Three of these experimental sites are in France, with ATLAS in Switzerland, although some of the ancillary cryogenic and access sites are in Switzerland. The largest of the experimental sites is the Prévessin site, also known as the North Area, which is the target station for non-collider experiments on the SPS accelerator. Other sites are the ones which were used for the UA1, UA2 and the LEP experiments (the latter are used by LHC experiments). " ( https://en.wikipedia.org/wiki/CERN )

>>8671374

=COVIDSAUCE=

For someone with better pedigree than I - perhaps to parse for leads & known ppl/places…. Report Released with little fanfarE, but lies at the heart of the matter. (?)

1. 3/12/2020

=Scientific Report on COVID ~3/12/2020=

Fairly benign, but hidden in plain sight:

1. No mentions of the 'malaria drug' or zinc…hmmmm

2. Curious if it might then be work towards a Trojan horse

3. Authors affil'd with Wuhan Institute of Virology - Twatters are not. Names might show up again ( or already have )

4. Sounds like some HegalianD, but perhaps not:

"moreover, it is too late to develop drugs against each virus behind epidemics33. Thus, it is imperative to develop new ideas, highly effective, broad-spectrum antiviral agents that can treat various viral infections."

Title

Novel and potent inhibitors targeting DHODH, a rate-limiting enzyme in de novo pyrimidine biosynthesis, are broad-spectrum antiviral against RNA viruses including newly emerged coronavirus SARS-CoV-2

Document ( PDF avail )

https://www.biorxiv.org/content/10.1101/2020.03.11.983056v1

Introduction

Acute viral infections, such as influenza virus, SARS-CoV, MERS-CoV, Ebola virus, Zika virus, and the very recent SARS-CoV-2 are an increasing and probably lasting global threat1. Broad-spectrum antivirals (BSA) are clinically needed for the effective control of emerging and re-emerging viral infectious diseases. However, although great efforts have been made by the research community to discover therapeutic antiviral agents for coping with such emergencies, specific and effective drugs or vaccines with low toxicity have been rarely reported2. Thus, unfortunately, there is still no effective drugs for the infection of the novel coronavirus SARS-CoV-2 at present, which outbreak in December 2019 firstly identified by several Chinese groups3-5, and now has quickly spread throughout China and to more than 90 other countries, infecting 101,923 patients and killing 3486 ones by March 7, 20206.

Images

`https://www.biorxiv.org/content/biorxiv/early/2020/03/12/2020.03.11.983056/F1.medium.gif

`https://www.biorxiv.org/content/biorxiv/early/2020/03/12/2020.03.11.983056/F2.medium.gif

`https://www.biorxiv.org/content/biorxiv/early/2020/03/12/2020.03.11.983056/F3.medium.gif

`https://www.biorxiv.org/content/biorxiv/early/2020/03/12/2020.03.11.983056/F4.medium.gif

`https://www.biorxiv.org/content/biorxiv/early/2020/03/12/2020.03.11.983056/F5.medium.gif

Results

The discovery of potent DHODH inhibitors with low toxicity in vivo and high antiviral efficacies in influenza-A-virus infected cells

Author Information

Rui Xiong2†, Leike Zhang3†, Shiliang Li2†, Yuan Sun3, Minyi Ding2, Yong Wang1, Yongliang Zhao1, Yan Wu3, Weijuan Shang3, Xiaming Jiang3, Jiwei Shan2, Zihao Shen2, Yi Tong2, Liuxin Xu2, Chen Yu1, Yingle Liu1, Gang Zou4, Dimitri Lavillete4, Zhenjiang Zhao2, Rui Wang2, Lili Zhu2, Gengfu Xiao3, Ke Lan1, Honglin Li2 and Ke Xu14

1 State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China

2 Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China

3 State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China

4 CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences; University of Chinese Academy of Sciences, 320 YueYang Road, Shanghai 200031, China

*Corresponding authors. Address correspondence and reprint requests to Dr. Ke Xu (E-mail: xuke03@whu.edu.cn, Tel: 86-27-68756997, Fax: 86-27-68754592) and Dr. Honglin Li (E-mail: hlli@ecust.edu.cn, Tel: 86-21-64250213, Fax: 86-21-64250213).

*these authors contribute equally to this work

>>8671374

=COVIDSAUCE CONT=

Discussion

Many different RNA viruses had caused epidemics and pandemics in the past 20 years, from avian influenza virus (AIV) H5N1 in 1997, SARS-CoV in 2002, pandemic H1N1 in 2009, MERS-CoV in 2012, AIV H7N9 in 2013, Ebola virus in 2013, Zika virus in 2016, to SARS-CoV-2 in 2019. Many of them are still prevalent in certain countries and SARS-CoV-2 continues causing huge damage to China and worldwide. The conventional one-bug-one-drug paradigm is insufficient to deal with the challenges of these emerging and re-emerging pathogenic viruses32……..Thus, it is imperative to develop new ideas, highly effective, broad-spectrum antiviral agents that can treat various viral infections.

More interestingly, we notice that compared with DNA viruses, RNA viruses need unique UMP but not TMP in their genomes. UMP is the particular nucleoside produced by DHODH, which means RNA viruses might be more sensitive to DHODH activity. SARS-CoV-2, for instance, has around 32% of UMP in its genome explaining why DHODHi are effective and superior to SARS-CoV-2. Nevertheless, the comparison between different viruses is worth to be studied in the future.

Moreover, A clinical study of 123 patients with COVID-19 ( when & where? ) showed that the percentage of patients with IL-6 above normal is higher in severe group45. In terms of treatment, immunomodulatory agents can reduce mortality and organ injury of severe influenza. However, these immunomodulatory are mostly non-specific to viral infection but rather a systemic regulation, such as corticosteroid, intravenous immunoglobulin (IVIG) or angiotensin receptor blockers46-49. Leflunomide and its active metabolite Teriflunomide have been approved for clinical treatment for excessive inflammatory diseases such as rheumatoid arthritis and multiple sclerosis50

Materials & Methods

Cell lines, virus, and drugs

MDCK, A549, Vero E6, Huh7 cells were obtained from the American Type Culture Collection (ATCC). 293FT cells were kindly provided by Paul Zhou (Institute Pasteur of Shanghai, China). BSR T7/5 cells stably expressing the T7 RNA polymerase gene were kindly provided by Gang Zou (Institute Pasteur of Shanghai, China). MDCK, A549, Vero E6, Huh7, 293FT cells were cultured in DMEM (Gibco) supplemented with 10%FBS (Gibco) and 1% P/S (Gibco). BSR T7/5 cells were cultured in GMEM (Gibco) supplemented with 10%FBS (Gibco), 1% L-Glutamine (Gibco), 2% MAA and 1% P/S (Gibco). The A/WSN/33 virus was generated by reverse genetics as previously described51. The A/Sichuan/1/2009(H1N1)(SC09), A/Jiangxi-Donghu/312/2006(H3N2), A/Guangzhou/333/99(H9N2) were kindly provided by Prof. Yuelong Shu (Chinese National Influenza Center). Zika virus SZ-WIV001 (KU963796) was kindly provided by Bo Zhang from Wuhan Virology Institute of CAS52. DHODH inhibitors S312 and S416 were synthesized using our previously reported synthetic routes27,53.

Twatz:

Carolyn Bertozzi

@CarolynBertozzi

Novel and potent inhibitors targeting DHODH, a rate-limiting enzyme in de novo pyrimidine biosynthesis, are broad-spectrum antiviral against RNA viruses including newly emerged coronavirus SARS-CoV-2 | bioRxiv https://t.co/Oxkc6hSWUi

13 Mar 2020

Felipe

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RT @biorxivpreprint: Novel and potent inhibitors targeting DHODH, a rate-limiting enzyme in de novo pyrimidine biosynthesis, are broad-spec…

13 Mar 2020

Biocheming

@Biocheming

RT @biorxivpreprint: Novel and potent inhibitors targeting DHODH, a rate-limiting enzyme in de novo pyrimidine biosynthesis, are broad-spec…

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>>8671608

Or if you are down with the NIV

Isa 30:33

Topheth—the place of burning—

has long been ready for the Assyrian king;

the pyre is piled high with wood.

The breath of the LORD, like fire from a =volcano=,

will set it ablaze.

>>8671746

troo

>>8671764

EXACTLY!!

>>8671450

Timberlake brought to you by Disney Ink

and LilWayne didn't kill himself