New viruses and old drugs: searching for treatments for COVID-19

By: Sandra Porter (@digitalbio)
Tue Feb 18, 2020
Novel Coronavirus SARS-CoV-2
This transmission electron microscope image shows 2019-nCoV, the virus that causes COVID-19, isolated from a patient in the U.S., and emerging from the surface of cells cultured in the lab.
Credit: NIAID-RML

Note:  the official name for the disease is COVID-19.  The virus that causes the disease is known as nCoV, and 2019-nCoV, and sometimes SARS-CoV-2.  

Resources for teaching:

1.  Coronavirus images from NIAID-RML, from the Public Health Image Library

2.  A map showing how the virus spread Healthmap.org/covid-19  and another map from Johns Hopkins University

Global spread of the novel coronavirus

3.  My favorite dashboard https://coronavirus.1point3acres.com/ 

4.  Current information on the outbreak:  CDC Coronavirus Disease 2019

5.  What is it like to have COVID-19?  What effects does it have on your body?  National Geographic:  Here's what coronavirus does to the body

6.  ViralZone SARS facts

7.  Life cycle SARS-CoV-2

Beta coronavirus life cycle

8.  The annotated Novel Coronavirus proteome from ViralZone

9.  SARS-CoV-2 DNA and RNA sequences at the NCBI

11.  Where did SARS-CoV-2 come from?

Reference sequence:  ref|NC_045512

Other coronaviruses:

gb|MG772933.1
gb|MN996532.1
gb|AY304486
gb|AY390556.1
gb|MT040335.1
gb|MK564475.1
ref|NC_006577.2
NC_005831.2
gb|KF294372.1
AY994055.1
AJ271965.2
NC_002645.1
NC_010646.1
NC_038294.1
NC_009021.1
NC_019843.3
NC_017083.1
NC_004718.3
NC_014470.1

Use Nucleotide blast

Pick discontinuous megablast as the program - this is best for cross species comparisons.

 

 

9.  nCoV phylogeny vs geography

Global spread and change in novel coronavirus genomes from Nextstrain.org

March 4th - Community transmission or travel?

April 3rd - COVID-19 in Iceland 

April 17th - States are not islands  or What happens in one state does not stay in that state.

 

10.  Structures:

6VXX - closed spike protein

6VYB - open spike protein

6M0J Receptor domain of SARS-CoV2 spike protein bound to ACE2

6YLA = SARS-CoV-2 spike bound to Fab CR3022

 

Science paper about neutralizing antibodies:  A Highly Conserved Cryptic Epitope in the Receptor-Binding Domains of SARS-CoV-2 and SARS-CoV

 

The SARS-CoV-2 spike protein and ACE2 and the ACE2 binding domain from SARS-CoV2 bound to a neutralizing antibody

10.  Structures of antibodies bound to SARS or MERS proteins.

11.  Companies working on COVID-19 tests, vaccines, treatments.

12.  Spread sheet for NCoV -19 proteins

 

Articles:

Galasiti Kankanamalage AC, Kim Y, Damalanka VC, et al. Structure-guided design of potent and permeable inhibitors of MERS coronavirus 3CL protease that utilize a piperidine moiety as a novel design elementEur J Med Chem. 2018;150:334–346. doi:10.1016/j.ejmech.2018.03.004

Kim Y, Liu H, Galasiti Kankanamalage AC, et al. Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor [published correction appears in PLoS Pathog. 2016 May;12(5):e1005650]. PLoS Pathog. 2016;12(3):e1005531. Published 2016 Mar 30. doi:10.1371/journal.ppat.1005531

Takano T, Akiyama M, Doki T, Hohdatsu T. Antiviral activity of itraconazole against type I feline coronavirus infectionVet Res. 2019;50(1):5. Published 2019 Jan 18. doi:10.1186/s13567-019-0625-3

 

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