An online repository of solvation thermodynamic and structural maps of SARS-CoV-2 targets
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An online repository of solvation thermodynamic and structural maps of SARS‑CoV‑2 targets Brian Olson3,4 · Anthony Cruz1,2 · Lieyang Chen1,3 · Mossa Ghattas1,2 · Yeonji Ji1,3 · Kunhui Huang1,3 · Steven Ayoub Jr6 · Tyler Luchko7 · Daniel J. McKay5 · Tom Kurtzman1,2,3 Received: 4 June 2020 / Accepted: 29 August 2020 © Springer Nature Switzerland AG 2020
Abstract SARS-CoV-2 recently jumped species and rapidly spread via human-to-human transmission to cause a global outbreak of COVID-19. The lack of effective vaccine combined with the severity of the disease necessitates attempts to develop small molecule drugs to combat the virus. COVID19_GIST_HSA is a freely available online repository to provide solvation thermodynamic maps of COVID-19-related protein small molecule drug targets. Grid inhomogeneous solvation theory maps were generated using AmberTools cpptraj-GIST, 3D reference interaction site model maps were created with AmberTools rism3d.snglpnt and hydration site analysis maps were created using SSTMap code. The resultant data can be applied to drug design efforts: scoring solvent displacement for docking, rational lead modification, prioritization of ligand- and protein- based pharmacophore elements, and creation of water-based pharmacophores. Herein, we demonstrate the use of the solvation thermodynamic mapping data. It is hoped that this freely provided data will aid in small molecule drug discovery efforts to defeat SARS-CoV-2. Keywords COVID-19 · Solvation thermodynamics · Virtual screening · Rational lead modification · Drug discovery
Introduction
* Tom Kurtzman [email protected] 1
Lehman College Department of Chemistry, 205 W Bedford Park Blvd, Bronx, NY 10468, USA
2
Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, 365 5th Avenue, New York, NY 10016, USA
3
Ph.D. Program in Biochemistry, The Graduate Center of the City University of New York, 365 5th Avenue, New York, NY 10016, USA
4
Department of Biology and Chemistry, County College of Morris, 214 Center Grove Rd, Randolph, NJ 07869, USA
5
Ventus Therapeutics, Frederick‑Banting, Montreal, QC H9S 2A1, Canada
6
Department of Chemistry and Biochemistry, California State University, Northridge, 18111 Nordhoff Street, Northridge, CA 91330, USA
7
Department of Physics and Astronomy, Center for Biological Physics, California State University, Northridge, 18111 Nordhoff Street, Northridge, CA 91330, USA
Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) recently emerged and spread to cause a pandemic of coronavirus disease 2019 (COVID-19). Given the failure to contain the initial outbreak, the global failure to restrain the pandemic, and the absence of an effective vaccine, we may need to identify existing drugs or develop new drugs to interrupt COVID-19 at a critical juncture. A number of targets may be of interest for the development of small molecule therapeutics for COVID-19: main protease (Mpro, 3CLpro), helicase (Nsp13), endoribonuclease (Nsp15), and 2′-O-
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