Potentiallead molecules against nCoV19

The commotion caused due to the outburst of the coronavirus is in an extreme need for the development of a therapeutic agent/biomarker against the causative agent. In this study, we have studied the virtual interaction between COVID-19 protease (6LU7) and commercially available drug molecules using the Discovery Studio software suite. The docking results showed a higher affinity of the drug molecules Ara-A (vidarabine) and Ara-C (cytarabine) towards the fifth binding pocket of the protease predicted by the software. We propose that these drugs can be used as therapeutic agents/biomarker in this case. 

The end of 2019 witnessed an outbreak of a fatal infection caused by the novel coronavirus in Wuhan, China. The subsequent periods beheld the spread of the virus across the boundaries of countries and continents. As of March 6th 97,884 confirmed cases and 3,382 deaths were reported across the world. With the unavailability of any proven antiviral drugs against the novel coronavirus medical professionals have attempted to just supportive care for the past periods. However, researchers across the world have reported that viral restraining mechanisms can be a possible solution until the perfect drug against the virus is developed. The three dimensional structures of the viral proteins were unavailable until the recent availability of the PDB ID: 6LU7 protease in the RCSB public domain. HIV inhibitory drugs although have been found to exhibit appreciative interactions with the protease the binding energies obtained are quite high. 

Here, we screened a number of commercial drugs obtained from seaweeds and sponges and studied their virtual interactions with the protease. Two drugs named Ara-A (commercial name: vidarabine; which is active against Herpes simplex virus and Varicella zoster virus) and Ara-C (commercial name: cytarabine; which is used to treat acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML) and Non-Hodgkin’s lymphoma) were especially analysed for their affinities towards the COVID-19 protease. In this study we chose 3-chymotrypsin like protease (3CL-protease)which is the main protease used to cleave polyproteins into replication-related proteins, as the target receptor. The molecular docking and visualisation was performed using the DiscoveryStudio (DS) software suit (version v18.1.100.18065). The protein purification, preparation and ligand preparation were performed automatically in the DS. Molecular Docking was executed for accurate docking of ligands into protein active sites using the Libdock module of the DS, which is a high-throughput docking algorithm that positions catalyst generated ligand conformations in the protein active site based on polar and apolar interaction sites (hotspots). The interaction poses were analysed manually considering the number of hydrogen bonds and libdock score. The binding energies of the selected poses were calculated subsequently. 

The proposed solution has the potential to affect the entire population affected by Coronavirus. There may be a number of molecules showing higher affinities to the protein but due to the emergency situation arising in the world which needs to be controlled, it is preferred to choose commercially available drugs, although possibilities of many efficient drugs can be further explored in future. 

The whole idea of open challenges is to pool in resources to address pandemics which threaten human health and well being. Currently about 3.5% of the people affected by corona are being claimed by death. The research community should come together to address this issue.

The solution proposed is uniques because of the fact that we focus on pre-existing drugs, that have passed the clinical trials. So the potential molecule of ours could be made available in market as early as possible.

113805. Lets hope the confirmed cases do not increase.

Laboratory requirements are too high.

Part of a for profit company working in a different domain altogether.

3 Full time and 1 temporary

Gain visibility for the concept and to build a team which can materialise the concept.

Any team who can complete the drug discovery and sent to market after completing the required lab tests.