COVID-19

Covid-19 is caused by SARS-CoV-2

  • COVID-19 is caused by a betacorona virus derivative: SARS-CoV-2, a positive-sense single-stranded RNA (30 kbp) virus
  • It is similar in its working and liabilities to SARS, MERS, common cold, and influenza
  • The 50-200 nm virions have four structural proteins
  • S (spike) enables the virus to attach to host cell membranes; E (envelope) & M (membrane) create the viral envelope; N (nucleocapsid) holding the RNA genome
  • Spike attaches to angiotensin converting enzyme 2 (ACE2) receptors of human cells for cell entry, it also uses basigin to gain cell entry
  • Initial spike protein attachment needs to be followed by priming by transmembrane protease, serine 2 (TMPRSS2): this host cell protease cuts spike protein, exposing a fusion peptide, allowing the virus to release RNA into the cell

 

Replication of SARS-CoV2

Positive-sense ssRNA viruses:

  • Have genetic material that can function both as a genome and as messenger RNA
  • Create viral replication complexes (VRCs) containing proteins of both viral and host cell origin and formed in association with intracellular membranes
  • Replicate positive-sense ssRNA genome through double-stranded RNA intermediates
    Divert the entire host cell translation machinery to the production of viral proteins, as a result of the very high affinity of viral genome's internal ribosome entry site (IRES) to host ribosomes
  • Disrupt normal protein synthesis by viral proteases degrading vital host translation initiation components
  • Encode RNA-dependent RNA polymerase (RdRP), a viral protein that synthesizes RNA from RNA template
  • Recruit host cell proteins during replication include RNA-binding proteins, chaperone proteins, and membrane remodeling and lipid synthesis proteins – exploiting the hosts secretory pathway for viral replication.
Electron microscope image of SARS-CoV-2019
This illustration was created at the Centers for Disease Control and Prevention (CDC), and reveals ultrastructural morphology exhibited by the 2019 Novel Coronavirus (2019-nCoV). Note the spikes that adorn the outer surface of the virus, which impart the look of a corona surrounding the virion, when analzyed by electron microscopy. CDC/ Alissa Eckert, MS; Dan Higgins, MAM - This media comes from the Centers for Disease Control and Prevention's Public Health Image Library (PHIL), with identification number #23312.
Curative treatment analysis

Using our broad suite of cell biology and (chemical) proteomics tools, we support faster drug discovery and development of antiviral compounds. A few examples, how we can help:

Immunization: creating antibodies that bind spike, envelop, or membrane protein

  • OmicScouts identifies binding viral proteins by pull down experiments using immobilized antibody / antiserum
  • We determine the affinity of multiple binders by competition analysis

Inhibiting virus attachment: by blocking or internalizing ACE2 or TMPRSS2

  • We quantify ACE2 and TMPRSS2 on the cell surface before and after treatment

Blocking RdRP to stop viral replication

  • We can quantify drug target affinity and selectivity in cell extracts (TargetScout™) and identify alternative (off-)targets and their affinity

Blocking viral protease

  • OmicScouts can quantify host protein cleavage
  • We can quantify drug target and alternative target affinity (TargetScout™)

Blocking assembly and shedding of viral particle

  • OmicScouts can quantify viral proteins in membrane vs. soluble fraction

 

Over the past years, we had numerous successful (chemical) proteomics projects related to antiviral drug discovery, including target identification and MoA deconvolution projects of anti-HIV and anti-influenza compounds.

Contact us for more information: info@omicscouts.com