tetano
Editor, Senior Moderator
Heliyon
. 2021 Mar;7(3):e06387.
doi: 10.1016/j.heliyon.2021.e06387. Epub 2021 Mar 1.
The study of antiviral drugs targeting SARS-CoV-2 nucleocapsid and spike proteins through large-scale compound repurposing
Xuqiao Hu[SUP] 1 2 [/SUP], Zhenru Zhou[SUP] 1 [/SUP], Fei Li[SUP] 3 [/SUP], Yang Xiao[SUP] 3 [/SUP], Zhaoyang Wang[SUP] 1 [/SUP], Jinfeng Xu[SUP] 1 [/SUP], Fajin Dong[SUP] 1 [/SUP], Hairong Zheng[SUP] 3 [/SUP], Rongmin Yu[SUP] 2 4 5 [/SUP]
Affiliations
Abstract
Contributing to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clinical treatment, a drug library encompassing approximately 3,142 clinical-stage or FDA-approved small molecules is profiled to identify the candidate therapeutic inhibitors targeting nucleocapsid protein (N) and spike protein (S) of SARS-CoV-2. 16 screened candidates with higher binding affinity are evaluated via virtual screening. Comparing to those under trial/temporarily used antivirus drugs (i.e., umifenovir, lopinavir), ceftriaxone, cefotaxime, and cefuroxime show higher binding affinities to the N-terminal domain of N protein (N-NTD), C-terminal domain of N protein (N-CTD), and receptor-binding domain of S protein (S-RBD). Cefotaxime and cefuroxime have high binding affinities towards S-RBD with angiotensin-converting enzyme 2 (ACE2) complex via influence the critical interface sites at the interface of S-RBD (Arg[SUP]403[/SUP], Tyr[SUP]453[/SUP], Trp[SUP]495[/SUP], Gly[SUP]496[/SUP], Phe[SUP]497[/SUP], Asn[SUP]501[/SUP]and Tyr[SUP]505[/SUP]) and ACE2 (Asn[SUP]33[/SUP], His[SUP]34[/SUP], Glu[SUP]37[/SUP], Asp[SUP]38[/SUP], Lys[SUP]353[/SUP], Ala[SUP]386[/SUP], Ala[SUP]387[/SUP], Gln[SUP]388[/SUP], Pro[SUP]389[/SUP], Phe[SUP]390[/SUP] and Arg[SUP]393[/SUP]) complex.
Keywords: Antiviral compounds; Drug screen and repurposing; SARS-CoV-2; Small molecule microarray chip.
. 2021 Mar;7(3):e06387.
doi: 10.1016/j.heliyon.2021.e06387. Epub 2021 Mar 1.
The study of antiviral drugs targeting SARS-CoV-2 nucleocapsid and spike proteins through large-scale compound repurposing
Xuqiao Hu[SUP] 1 2 [/SUP], Zhenru Zhou[SUP] 1 [/SUP], Fei Li[SUP] 3 [/SUP], Yang Xiao[SUP] 3 [/SUP], Zhaoyang Wang[SUP] 1 [/SUP], Jinfeng Xu[SUP] 1 [/SUP], Fajin Dong[SUP] 1 [/SUP], Hairong Zheng[SUP] 3 [/SUP], Rongmin Yu[SUP] 2 4 5 [/SUP]
Affiliations
- PMID: 33688584
- PMCID: PMC7919521
- DOI: 10.1016/j.heliyon.2021.e06387
Abstract
Contributing to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clinical treatment, a drug library encompassing approximately 3,142 clinical-stage or FDA-approved small molecules is profiled to identify the candidate therapeutic inhibitors targeting nucleocapsid protein (N) and spike protein (S) of SARS-CoV-2. 16 screened candidates with higher binding affinity are evaluated via virtual screening. Comparing to those under trial/temporarily used antivirus drugs (i.e., umifenovir, lopinavir), ceftriaxone, cefotaxime, and cefuroxime show higher binding affinities to the N-terminal domain of N protein (N-NTD), C-terminal domain of N protein (N-CTD), and receptor-binding domain of S protein (S-RBD). Cefotaxime and cefuroxime have high binding affinities towards S-RBD with angiotensin-converting enzyme 2 (ACE2) complex via influence the critical interface sites at the interface of S-RBD (Arg[SUP]403[/SUP], Tyr[SUP]453[/SUP], Trp[SUP]495[/SUP], Gly[SUP]496[/SUP], Phe[SUP]497[/SUP], Asn[SUP]501[/SUP]and Tyr[SUP]505[/SUP]) and ACE2 (Asn[SUP]33[/SUP], His[SUP]34[/SUP], Glu[SUP]37[/SUP], Asp[SUP]38[/SUP], Lys[SUP]353[/SUP], Ala[SUP]386[/SUP], Ala[SUP]387[/SUP], Gln[SUP]388[/SUP], Pro[SUP]389[/SUP], Phe[SUP]390[/SUP] and Arg[SUP]393[/SUP]) complex.
Keywords: Antiviral compounds; Drug screen and repurposing; SARS-CoV-2; Small molecule microarray chip.