Heliyon . The study of antiviral drugs targeting SARS-CoV-2 nucleocapsid and spike proteins through large-scale compound repurposing

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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 ^{1 2} , Zhenru Zhou ¹ , Fei Li ³ , Yang Xiao ³ , Zhaoyang Wang ¹ , Jinfeng Xu ¹ , Fajin Dong ¹ , Hairong Zheng ³ , Rongmin Yu ^{2 4 5}



Affiliations

• PMID: 33688584
• PMCID: PMC7919521
• DOI: 10.1016/j.heliyon.2021.e06387

Free PMC article

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 (Arg⁴⁰³, Tyr⁴⁵³, Trp⁴⁹⁵, Gly⁴⁹⁶, Phe⁴⁹⁷, Asn⁵⁰¹and Tyr⁵⁰⁵) and ACE2 (Asn³³, His³⁴, Glu³⁷, Asp³⁸, Lys³⁵³, Ala³⁸⁶, Ala³⁸⁷, Gln³⁸⁸, Pro³⁸⁹, Phe³⁹⁰ and Arg³⁹³) complex.

Keywords: Antiviral compounds; Drug screen and repurposing; SARS-CoV-2; Small molecule microarray chip.