Drug design and repurposing with DockThor-VS web server focusing on SARS-CoV-2 therapeutic targets and their non-synonym variants

被引：91

作者：

Guedes, Isabella A. ^{[1
]}

Costa, Leon S. C. ^{[1
]}

dos Santos, Karina B. ^{[1
]}

Karl, Ana L. M. ^{[1
]}

Rocha, Gregorio K. ^{[2
]}

Teixeira, Iury M. ^{[1
]}

Galheigo, Marcelo M. ^{[1
]}

Medeiros, Vivian ^{[1
]}

Krempser, Eduardo ^{[3
]}

Custodio, Fabio L. ^{[1
]}

Barbosa, Helio J. C. ^{[1
]}

Nicolas, Marisa F. ^{[4
]}

Dardenne, Laurent E. ^{[1
]}

机构：

[1] Natl Lab Sci Comp LNCC, Grp Modelagem Mol Sistemas Biol GMMSB, Petropolis, RJ, Brazil

[2] Inst Fed Fluminense IFF, Macae, RJ, Brazil

[3] Fundacao Oswaldo Cruz Fiocruz, Rio De Janeiro, RJ, Brazil

[4] Natl Lab Sci Comp LNCC, Lab Bioinformat Labinfo, Petropolis, RJ, Brazil

来源：

SCIENTIFIC REPORTS | 2021年 / 11卷 / 01期

关键词：

DEPENDENT RNA-POLYMERASES; RECEPTOR-BINDING; SPIKE PROTEIN; CORONAVIRUS; SARS; COVID-19; DOMAIN; IVERMECTIN; REPLICATION; FIDAXOMICIN;

D O I：

10.1038/s41598-021-84700-0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The COVID-19 caused by the SARS-CoV-2 virus was declared a pandemic disease in March 2020 by the World Health Organization (WHO). Structure-Based Drug Design strategies based on docking methodologies have been widely used for both new drug development and drug repurposing to find effective treatments against this disease. In this work, we present the developments implemented in the DockThor-VS web server to provide a virtual screening (VS) platform with curated structures of potential therapeutic targets from SARS-CoV-2 incorporating genetic information regarding relevant non-synonymous variations. The web server facilitates repurposing VS experiments providing curated libraries of currently available drugs on the market. At present, DockThor-VS provides ready-for-docking 3D structures for wild type and selected mutations for Nsp3 (papain-like, PLpro domain), Nsp5 (Mpro, 3CLpro), Nsp12 (RdRp), Nsp15 (NendoU), N protein, and Spike. We performed VS experiments of FDA-approved drugs considering the therapeutic targets available at the web server to assess the impact of considering different structures and mutations to identify possible new treatments of SARS-CoV-2 infections. The DockThor-VS is freely available at www.dockthor.lncc.br.

引用

页数：20

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