Dataset Information

A multi-pronged approach targeting SARS-CoV-2 proteins using ultra-large virtual screening.

ABSTRACT: The unparalleled global effort to combat the continuing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic over the last year has resulted in promising prophylactic measures. However, a need still exists for cheap, effective therapeutics, and targeting multiple points in the viral life cycle could help tackle the current, as well as future, coronaviruses. Here, we leverage our recently developed, ultra-large-scale in silico screening platform, VirtualFlow, to search for inhibitors that target SARS-CoV-2. In this unprecedented structure-based virtual campaign, we screened roughly 1 billion molecules against each of 40 different target sites on 17 different potential viral and host targets. In addition to targeting the active sites of viral enzymes, we also targeted critical auxiliary sites such as functionally important protein-protein interactions.

SUBMITTER: Gorgulla C

PROVIDER: S-EPMC7783459 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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A multi-pronged approach targeting SARS-CoV-2 proteins using ultra-large virtual screening.

Gorgulla Christoph C Padmanabha Das Krishna M KM Leigh Kendra E KE Cespugli Marco M Fischer Patrick D PD Wang Zi-Fu ZF Tesseyre Guilhem G Pandita Shreya S Shnapir Alec A Calderaio Anthony A Gechev Minko M Rose Alexander A Lewis Noam N Hutcheson Colin C Yaffe Erez E Luxenburg Roni R Herce Henry D HD Durmaz Vedat V Halazonetis Thanos D TD Fackeldey Konstantin K Patten J J JJ Chuprina Alexander A Dziuba Igor I Plekhova Alla A Moroz Yurii Y Radchenko Dmytro D Tarkhanova Olga O Yavnyuk Irina I Gruber Christian C Yust Ryan R Payne Dave D Näär Anders M AM Namchuk Mark N MN Davey Robert A RA Wagner Gerhard G Kinney Jamie J Arthanari Haribabu H

iScience 20210105 2

The unparalleled global effort to combat the continuing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic over the last year has resulted in promising prophylactic measures. However, a need still exists for cheap, effective therapeutics, and targeting multiple points in the viral life cycle could help tackle the current, as well as future, coronaviruses. Here, we leverage our recently developed, ultra-large-scale <i>in silico</i> screening platform, VirtualFlow, to search for ...[more]

PMID: 33426509

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Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), previously known as 2019 novel coronavirus (2019-nCoV), has spread rapidly across the globe, creating an unparalleled global health burden and spurring a deepening economic crisis. As of July 7th, 2020, almost seven months into the outbreak, there are no approved vaccines and few treatments available. Developing drugs that target multiple points in the viral life cycle could serve as a strategy to tackle the current as well as future coronavirus pandemics. Here we leverage the power of our recently developed in silico screening platform, VirtualFlow, to identify inhibitors that target SARS-CoV-2. VirtualFlow is able to efficiently harness the power of computing clusters and cloud-based computing platforms to carry out ultra-large scale virtual screens. In this unprecedented structure-based multi-target virtual screening campaign, we have used VirtualFlow to screen an average of approximately 1 billion molecules against each of 40 different target sites on 17 different potential viral and host targets in the cloud. In addition to targeting the active sites of viral enzymes, we also target critical auxiliary sites such as functionally important protein-protein interaction interfaces. This multi-target approach not only increases the likelihood of finding a potent inhibitor, but could also help identify a collection of anti-coronavirus drugs that would retain efficacy in the face of viral mutation. Drugs belonging to different regimen classes could be combined to develop possible combination therapies, and top hits that bind at highly conserved sites would be potential candidates for further development as coronavirus drugs. Here, we present the top 200 in silico hits for each target site. While in-house experimental validation of some of these compounds is currently underway, we want to make this array of potential inhibitor candidates available to researchers worldwide in consideration of the pressing need for fast-tracked drug development.

Dataset Information

A multi-pronged approach targeting SARS-CoV-2 proteins using ultra-large virtual screening.

Publications

A multi-pronged approach targeting SARS-CoV-2 proteins using ultra-large virtual screening.

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