SILVER Topical News

SILVER MERS-coronavirus outbreak pipeline

In June 2012, a previously unknown coronavirus was isolated from a patient in Saudi Arabia...

In June 2012, a previously unknown coronavirus was isolated from a patient in Saudi Arabia (Zaki et al., 2012; van Boheemen et al., 2012), and retrospectively this virus was linked to an earlier small outbreak of severe respiratory disease in Jordan (April 2012). Up to January 2014, WHO has registered at least 178 (laboratory-confirmed) cases of infection with the virus. These infections are linked to multiple, geographically distinct locations in the Middle East, although the viral reservoir remains to be identified. By now significant evidence for limited human-to-human transmission has accumulated. In particular the high case-fatality rate, 75 deaths have been recorded, has raised considerable global concerns that we might be confronted with a repeat of the SARS episode of 2003. No vaccines or antiviral drugs are available against the newly identified betacoronavirus, which has now been named Middle East Respiratory Syndrome Coronavirus (MERS-CoV) (de Groot et al., 2013). Also in Europe, several small clusters of MERS-CoV infection have occurred, e.g. in UK, France, Italy an Spain, due to returning travelers. In addition, MERS patients have been transferred from the Middle East to various European hospitals often before the proper diagnosis had been made and quarantine measures could be implemented.

 1-Characterization of the MERS-coronavirus

The properties of MERS-CoV are currently being studied by several SILVER partners (in collaboration with external partners). This has resulted in (among other achievements) the analysis of the complete genome sequence of MERS-CoV, characterization of virus growth, and the discovery of the MERS-CoV entry receptor (van Boheemen et al., 2012; de Wilde et al., 2013; Raj et al., 2013). In addition, the knowledge and technologies developed by several SILVER partners through studying other coronaviruses (such as SARS-CoV, HCoV-NL63, and batCoV-HKU4) will aid in the further characterization of MERS-CoV.

 2-Screening for MERS-coronavirus inhibitors

In vitro and in vivo assays are currently being used to screen for compounds that efficiently inhibit MERS-CoV replication. Screening of antiviral compound libraries available within SILVER has yielded the first set of hits, which is currently investigated in more detail. In addition, analysis of virus-host interactions, structural biology and reverse genetics are being used to define the most suitable targets for antiviral treatment.

 3- International collaboration

Investigators from SILVER, other European virus research networks like EMPERIE, ANTIGONE, PREDEMICS, EVA and PREPARE, and additional European research groups that are worldwide leaders on different aspects of coronavirus research have joined the MERS-CoV Initiative (MERCI). MERCI research goals:

  • Establish the source of MERS-CoV;
  • Establish knowledge of MERS-CoV molecular biology (including characterization of viral enzymes and MERS-CoV interplay with the host’s immune system);
  • Determine the pathogenesis of MERS-CoV-associated disease in severe human cases;
  • Establish the risk and risk promoting factors of human-to-human transmission of the virus;
  • Establish true incidence of MERS-CoV infections and developing appropriate and sensitive diagnostic assays;
  • Develop management plans for the prevention of MERS-CoV spread in Europe;
  • (Further) develop prototype vaccines (e.g., vaccine candidate for MERS-CoV using synthetic biology and a reverse genetics system);
  • Develop small molecule inhibitors of virus replication (as a first line of defence);
  • Develop suitable animal models for use in the above studies.

More information can be found in the following statement...

MERS-CoV Initiative (MERCI) pdf :
PDF - 282.5 kb
The research leading to these results has received funding from the European Union Seventh Programme (FP7 2007/2013) under grant agreement n°260644-SILVER