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"The live SARS-like coronavirus SL-CoV-WIV1 has been isolated for the first time from bat droppings; and such virus has been confirmed to invade the host cells through the ACE2 of human beings..."

Bat Severe Acute Respiratory Syndrome-Like Coronavirus WIV1
Encodes an Extra Accessory Protein, ORFX, Involved in Modulation of the Host Immune Response. (2016) #ZhengLiShi #PeterDaszak #EcoHealth
Funding: #NIAID 110964

In this study, we have developed a fast and cost-effective method
for reverse genetics of coronaviruses by combining two approaches developed by others..As the genomes can be divided into multiple short fragments, mutations can be introduced into individual
fragments easily.

FUNDING INFORMATION
This work, including the efforts of #ZhengLiShi, was funded by (NSFC) (81290341 and 31321001). This work, including the efforts of #PeterDaszak , was funded by Foundation for the National Institutes of Health
NIAID: R01AI110964

Coexistence of multiple #coronaviruses in several #bat colonies in an abandoned #mineshaft. #WIV1 #Yunnan #RaBtCov/4991

Only two sequences detected in this study were homologous to betacoronaviruses. One of them (RaBtCoV/4991) was detected in a R.affinis sample & was related to
SL-CoV.b.3.The conserved 440-bp RdRp fragment of #RaBtCoV/4991 had 89% nt identity and 95% aa identity with SL-CoV Rs672

#Funded by NIAID R01AI110964.
#Baric #Daszak #ZhengLiShi #Wuhan #WIV1 #SCHO14 #RhinolophusAffinis #SARSCoV2
#COVID19

Isolation and characterization of a #bat SARS-like #coronavirus that uses the #ACE2 receptor. #SHC014
#Rs3367 #WIV1

the ability of SL-CoV-WIV1 to use human #ACE2 argues against the
necessity of this step for SL-CoV-WIV1 and suggests that direct bat-to-human infection is a plausible scenario for some bat SL-CoVs. #Sars #WIV1 #BJ01 #SProtein

Most importantly, we report the first recorded isolation of a live SL-COV-WIV1 from bat faecal samples in Vero E6 cells... #ORF1b #virus #Genome

#NIAID award number R01AI079231
#Daszak #ZhengLiShi #coronavirus #COVID19 #WuhanInstituteVirology
#EcoHealth ➡️September 18 2013

New #SARS -like #Coronavirus Discovered in Chinese HorseshoeBats. #EcoHealth #PeterDaszak #RalphBaric #ZhengLiShi #USAID #PREDICT #WuhanInstituteVirology #ACE2 #WIV1 NIH R01AI079231
globalbiodefense.com/2013/11/04/new…

Isolation and Characterization of a #Novel Bat #Coronavirus closely related to the direct progenitor of #SARS coronavirus. #Daszak #ZhengLiShi 🔸️December 30 2013
#ACE2 #WIV1 #SH014 #WIV16

The overall nt #sequence of #WIV16 shared 96% identity,
64 higher than any previously reported #Bat #SLCoVs .. WIV16 is the closet progenitor of the #SARS -CoV in 68 most proteins, particularly in the #SProtein . #RBD
#GenBank number: KT444582

#WIV16 S gene is likely a
#recombinant of #WIV1 and a recent ancestor of #SARS -CoV.
Funding: NIAID R01AI110964 to #PD

#Viral Metagenomics, #Protein Structure, and #ReverseGenetics: Key Strategies for Investigating #Coronaviruses . #HorseshoeBats #Sars #NL63

Importantly, three CoVs #SHC014 #WIV1 & #WIV16 have been shown
experimentally to bind civet and #Human #ACE2 , suggesting that the #epidemic strain #SARS-CoV may have emerged from one of the quasi-species pools in the SARS-like #CoV population. #PREDICT #ACE2 #Glycoprotein

The #SHC014-MA15 & #WIV1-MA15 #Chimeras could #Replicate in #Vitro and in #Vivo, suggesting that these #Viruses are poised for #Human Emergence. #ORF1b #Spike

#ReverseGenetic studies involving the creation of these #Chimeras raise #Biosafety concerns, particularly in light of the recent 'PAUSE ON GAIN OF FUNCTION' associated with #Influenza & #Coronaviruses . #Baric #NIH #NIAID

Applying insights from #Viral #Metagenomics, Structure, and #ReverseGenetics, Offer
the Opportunity to Utilize the #CC to Identify #Host #Genes that Contribute to Emergence of #Zoonotic #CoVs . FUNDING:
NIH under awards U19 AI109761

#Shc014 #RsShc014 #Rs3367 ➡️2015 #UniversityNorthCarolina #WuhanInstituteVirology #Baric #SL-SHC014-MA15 #Nucleotides #SARSCoV2 #CollabrativeCross #GOF #NIH #NIAID

Doing Diligence to Assess the Risks and Benefits of Life Sciences #GainofFunction Research .
obamawhitehouse.archives.gov/blog/2014/10/1…

Moving Beyond #Metagenomics to find the next #Pandemic #Virus :
"The experimental findings suggest that #WIV1-CoV is a potential
'THREAT' to #Humans. If this virus emerged as a human #pathogen,
would we be prepared to prevent or treat infections?" #SHC014-MA15

If #WIV1-CoV or a similar virus were to spread in #Humans , #vaccination with inactivated #SARS-CoV would 'NOT' protect against #infection. #SHC014

#SARS -like Cluster of Circulating #Bat #Coronavirus pose threat for
#Human Emergence. #Baric 🔸️#ZhengLiShi ➡️ ZLS provided #SHC014 #Spike sequences & #Plasmids .

#SHC014 -MA15 was viable and replicated to high titers in #Vero cells. #ACE2 #WIV1 The Data Confirm the Ability of #SHC014 Spike to #Infect #Human Airway Cells and Underscore the Threat of Coss-Species #Transmission .

Theories Imply that Pools of #Bat #CoVs are Limited and #Host Range #Mutations are Both Random & Rare, Reducing the Likelihood of Future Emergence Events in #Humans. #SpikeProteins

Relative to the Urbani #Spike - #MA15 CoV, #SHC014-MA15 Constitutes a Gain in #Pathogenesis. Based on These Findings, Review Panels May Deem Similar Studies Too Risky to Pursue as Increased #Pathogenicity in Mammalian Models Cannot be Excluded. #USAMRIID #ChimericVirus

#UniversityNorthCarolina #Biosafety #Biosecurity #BSL3
#NIH U19AI109761 -
#RSB U19AI107810 ➡️National Natural Science Foundation of China Award 81290341 🔸️(ZLS)

#WIV1 #RsShc014 #MA15 #ORF1b #Sars #HumanInfection

Molecular Determinants of Severe Acute Respiratory Syndrome
#Coronavirus Pathogenesis and Virulence in #Young and #Aged Mouse Models of #Human Disease. ➡️ #Baric et al October 29, 2011.

The #SARS-CoV is a zoonotic pathogen that emerged in #Guangdong Province in Southeast #China in the fall of 2002. Age was a major cofactor enhancing morbidity, as evidenced by 50% mortality rates in immunosenescent populations 65 years of age....

We have developed several robust #mouse models for #SARS-CoV infection that capture the #age-related disease phenotypes
seen during acute SARS-CoV #infection in #humans .
#MA15 #ACE2

Using a #SARS-CoV molecular clone, we reconstructed a recombinant mouse-adapted SARS-CoV ➡️ #rMA15 . In 12-month-old #BALB/c mice...
rMA15 caused 100% #mortality .
#UNC #Recombinant #virus

In #humans, #age was a major
cofactor associated with #disease severity following #SARS-CoV #infection .

ACKNOWLEDGMENTS: This work was generously supported by NIH #grant AI075297 to R.S.#Baric, and M. Frieman was supported by NIH training grant F32 AI066542. This research was supported in part by the Intramural Research Program of the #NIAID, #NIH.

A Mouse-Adapted #SARS- #Coronavirus Causes #Disease & #Mortality in BALB/c # Mice .
🔸️#Baric et al. January 12 2007.
The #MA15 #virus will enhance the use of the mouse model for SARS because infection with this virus in mice reproduces many aspects of severe human disease.

The #MA15 virus has six coding #mutations associated with adaptation and increased virulence; when introduced into a # recombinant #SARS-CoV, these mutations result in a highly virulent and lethal #virus #rMA15 .

The Institute for #Genomic Research (Rockville, Maryland, United States), under a National
Institute of Allergy & Infectious Diseases #NIAID contract, confirmed the same six mutations in the #MA15 sequence compared with those in the #SARS-CoV #Urbani sequence. #Genome

Groups of four mice were inoculated with a lethal dose of
#MA15 virus or with #SARS-CoV (Urbani) (105 TCID50/mouse).
Mice inoculated with MA15 #virus did not survive past day 4. #MA15-ORF1ab

Finally and most importantly, #MA15 virus infection of young BALB/c mice provides many elements that replicate observations in acute and chronic cases of #SARS infection in #humans .

The #GenBank accession numbers for the #viruses and sequences discussed in this paper are mouse adapted SARS-CoV #MA15 sequence (DQ497008) & SARS-Cov
(Urbani) (AY278741).

US #PATENT 9884895 : "Methods and Compositions for #Chimeric #Coronavirus #Spike #Proteins." - Inventor: #RalphBaric . #RsSHC014 #Rs3367 #WIV1 #rMA15 #MA15-GD03S.

#coronaviruses that can be used to produce the #chimeric coronavirus spike protein of this invention include Bat #SARS CoV, as well as any other subgroup 2b coronavirus now known, or later identified, and any combination thereof. patents.google.com/patent/US98848…

#Covid_19 - An Orally Bioavailable Broad-Spectrum Antiviral Inhibits #SARSCoV2 in Human Airway Epithelial Cell Cultures and #Multiple #Coronaviruses in #Mice .
🔸️#Baric April 29, 2020.
#VeroE6 #SHC014 #MA15 #ACE2 #UNC #GilheadSciences #SARS-MA15 #WIV1

stm.sciencemag.org/content/12/541…

#Remdesivir, developed through a #UNC-Chapel Hill partnership, proves effective against #COVID-19 in #NIAID #Human clinical trials.
"We were seeking ‘one drug for many bugs.’ When this pandemic arrived.." #Baric #Fauci
sph.unc.edu/sph-news/remde…

Dr.#Baric's lab has a 6 year head start developing #Remdesivir for treating #Coronaviruses. #UNC #GilheadSciences
wunc.org/post/unc-lab-m…

@WHO

@WHO

"There’s only one drug right now that we think may have real efficacy, " said #BruceAylward, an assistant Director General with the @WHO . "And that’s #Remdesivir ". #Baric #UNC #GilheadSciences #MA15 #Covid_19