New structural target against COVID-19

A new structural target for drug development against COVID-19 has been unveiled today by Sibylla Biotech in collaboration with the Italian National Institute of Nuclear Physics (INFN), the University of Trento and University of Perugia.The breakthrough drug discovery strategy pioneered by Sibylla in this study would not only promise to reduce the risk of drug resistance and harmful side effects, but it also opens new avenues for the therapy of other viral and non-viral diseases.The results have been published today on the open access preprint archive arXiv:2004.13493.

Sibylla Biotech has discovered one structural drug discovery target, showing two potential drug binding pockets in the intermediate folding structures of ACE2, a protein normally found on the surface of lung cells (and of other organs such as heart and gut), exploited by the SARS-CoV-2 virus as its entry gate to the cell.

These coronavirus disease ‘Achilles heel’ has been alreadly screened by Sibylla against 9187 active pharmaceutical ingredients, either already approved or under clinical trials but alreadly commercially available, able to be quickly repurposed. Among them, Sibylla has already found 35 promising molecules, including some belonging to the hydroxychloroquine family, suspected of being capable of blocking viral replication in vitro. This molecule, its six analogues and the other 35 predicted by the calculations will be further evaluated in the laboratory.

The activity of hydroxychloroquine and its analogues on COVID-19 is extremly controversial to say the least, and computer-based screening are only a first line of circumstancial evidence that has to back up by in vitro and in vivo experiments. However, such results could in principle be useful in understanding the action of already known molecules against the virus. Sibylla Biotech freely provides the atomic level reconstruction of the binding pockets on request, so that owners of proprietary molecules can further test them in silico and in the lab.

This breakthrough by Sibylla Biotech could be an important result for the development of antiviral drugs, but it is also opening avenues towards the therapy of many other diseases. As stated by Sibylla CEO Lidia Pieri:

“In this historical moment, whoever has an idea against COVID-19 and the means to get it through, even if partially, must get in the game. There is no other choice.

The extraordinary response of INFN, that generously offered us substantial computing resources, shows that great things are possible. Today’s results are by no means definitive, but we will soon have answers from the laboratories. The knowledge we obtained is now freely available to the community: everyone can build on them towards a cure. In the meantime, we keep going with research as much as possible with our means.”