COVID-19 DRUG DESIGN IN INDIA
There is another side to the government response to the SAR-CoV2 as the Covid19 virus is also known. These are from the molecular biologists and pharmacologists, who are finding an antivirus to it. An invitation in the mail to participate in a drug design hackathon (DDH) was most intriguing, and I would like to share what I gathered, from the statements made by the scientists, who have been working on the problem. There are Indian herbal doctors offering Ashwagandha (Withania Somnifera) and also a Chinese herbal remedy based on the Empress tree (Paulownia Tomentosa). Also numerous sythesized compounds, that have been used for Middle Eastern respiratory syndrome (MERS) and the earlier version of SARS. The link to the DDH is at https://innovateindia.mygov.in/ddh2020/
The Protein Data Base (PDB) is a database repository for all the proteins, and researchers are attempting to identify the structure of the novel parts of the virus that has stormed the planet. Many parts of the virus, such as the spike and membrane appear to be identified, but there are missing elements that have not been crystallized and sequenced. It is common knowledge, that a protein is made up a sequence of amino acids, and there are 18 of these amino acids. The arrangement of amino acide, or signature is unique, and the challenge is to identify the sequence, so that one may inhibit the influence of the virus on human receptors. This identification of the protein folding, is complicated by mutations.
Various companies in the field such as CDAC, Schrodinger, ChemAxon, obtibrium, BioSolveIT, and Cresset Software have provided tools free of cost, to the participants in the hackathon. Problem Statements have been provided, with expectations of the three dimensional structural model, and information required about the target molecule. In Silico testing and search for the hit molecule is about using the computer to ascertain which drug molecule will inhibit the virus from entering into the human cell. Molecular Docking (MD) is a method used to try out a large number of small molecules from a database, and see which ones are suitable for a vaccine.
Simplified Molecular Input Line Entry System is a notation or nomenclature that allows a user to represent a chemical structure in a way that can be parsed by the computer. This is compact way of representing the molecular structure of a drug molecule. The Deep Learning challenge is to try to use regression and logistics regression methods on a large database of drug molecules to determine which one inhibits the activity of the virus from entering the host cell in the human body. For example the dataset below in Table 1 shows a list of molecules and how they effect the heart. It is from the government sponsored hackathon. Prizes are being offered as an incentive for best prediction models for such datasets.