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Identification of SARS-CoV-2 Cell Entry Inhibitors by Drug Repurposing Using in silico Structure-Based Virtual Screening Approach.
Front Immunol. 2020; 11:1664.FI

Abstract

The rapidly spreading, highly contagious and pathogenic SARS-coronavirus 2 (SARS-CoV-2) associated Coronavirus Disease 2019 (COVID-19) has been declared as a pandemic by the World Health Organization (WHO). The novel 2019 SARS-CoV-2 enters the host cell by binding of the viral surface spike glycoprotein (S-protein) to cellular angiotensin converting enzyme 2 (ACE2) receptor. The virus specific molecular interaction with the host cell represents a promising therapeutic target for identifying SARS-CoV-2 antiviral drugs. The repurposing of drugs can provide a rapid and potential cure toward exponentially expanding COVID-19. Thereto, high throughput virtual screening approach was used to investigate FDA approved LOPAC library drugs against both the receptor binding domain of spike protein (S-RBD) and ACE2 host cell receptor. Primary screening identified a few promising molecules for both the targets, which were further analyzed in details by their binding energy, binding modes through molecular docking, dynamics and simulations. Evidently, GR 127935 hydrochloride hydrate, GNF-5, RS504393, TNP, and eptifibatide acetate were found binding to virus binding motifs of ACE2 receptor. Additionally, KT203, BMS195614, KT185, RS504393, and GSK1838705A were identified to bind at the receptor binding site on the viral S-protein. These identified molecules may effectively assist in controlling the rapid spread of SARS-CoV-2 by not only potentially inhibiting the virus at entry step but are also hypothesized to act as anti-inflammatory agents, which could impart relief in lung inflammation. Timely identification and determination of an effective drug to combat and tranquilize the COVID-19 global crisis is the utmost need of hour. Further, prompt in vivo testing to validate the anti-SARS-CoV-2 inhibition efficiency by these molecules could save lives is justified.

Authors+Show Affiliations

Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, India.Division of Biological Standardization, Indian Veterinary Research Institute, Bareilly, India.Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, India.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32754161

Citation

Choudhary, Shweta, et al. "Identification of SARS-CoV-2 Cell Entry Inhibitors By Drug Repurposing Using in Silico Structure-Based Virtual Screening Approach." Frontiers in Immunology, vol. 11, 2020, p. 1664.
Choudhary S, Malik YS, Tomar S. Identification of SARS-CoV-2 Cell Entry Inhibitors by Drug Repurposing Using in silico Structure-Based Virtual Screening Approach. Front Immunol. 2020;11:1664.
Choudhary, S., Malik, Y. S., & Tomar, S. (2020). Identification of SARS-CoV-2 Cell Entry Inhibitors by Drug Repurposing Using in silico Structure-Based Virtual Screening Approach. Frontiers in Immunology, 11, 1664. https://doi.org/10.3389/fimmu.2020.01664
Choudhary S, Malik YS, Tomar S. Identification of SARS-CoV-2 Cell Entry Inhibitors By Drug Repurposing Using in Silico Structure-Based Virtual Screening Approach. Front Immunol. 2020;11:1664. PubMed PMID: 32754161.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of SARS-CoV-2 Cell Entry Inhibitors by Drug Repurposing Using in silico Structure-Based Virtual Screening Approach. AU - Choudhary,Shweta, AU - Malik,Yashpal S, AU - Tomar,Shailly, Y1 - 2020/07/10/ PY - 2020/04/17/received PY - 2020/06/22/accepted PY - 2020/8/6/entrez PY - 2020/8/6/pubmed PY - 2020/8/22/medline KW - ACE2 KW - COVID-19 KW - RNA viruses KW - SARS-CoV-2 KW - drug-repurposing KW - receptor-binding domain SP - 1664 EP - 1664 JF - Frontiers in immunology JO - Front Immunol VL - 11 N2 - The rapidly spreading, highly contagious and pathogenic SARS-coronavirus 2 (SARS-CoV-2) associated Coronavirus Disease 2019 (COVID-19) has been declared as a pandemic by the World Health Organization (WHO). The novel 2019 SARS-CoV-2 enters the host cell by binding of the viral surface spike glycoprotein (S-protein) to cellular angiotensin converting enzyme 2 (ACE2) receptor. The virus specific molecular interaction with the host cell represents a promising therapeutic target for identifying SARS-CoV-2 antiviral drugs. The repurposing of drugs can provide a rapid and potential cure toward exponentially expanding COVID-19. Thereto, high throughput virtual screening approach was used to investigate FDA approved LOPAC library drugs against both the receptor binding domain of spike protein (S-RBD) and ACE2 host cell receptor. Primary screening identified a few promising molecules for both the targets, which were further analyzed in details by their binding energy, binding modes through molecular docking, dynamics and simulations. Evidently, GR 127935 hydrochloride hydrate, GNF-5, RS504393, TNP, and eptifibatide acetate were found binding to virus binding motifs of ACE2 receptor. Additionally, KT203, BMS195614, KT185, RS504393, and GSK1838705A were identified to bind at the receptor binding site on the viral S-protein. These identified molecules may effectively assist in controlling the rapid spread of SARS-CoV-2 by not only potentially inhibiting the virus at entry step but are also hypothesized to act as anti-inflammatory agents, which could impart relief in lung inflammation. Timely identification and determination of an effective drug to combat and tranquilize the COVID-19 global crisis is the utmost need of hour. Further, prompt in vivo testing to validate the anti-SARS-CoV-2 inhibition efficiency by these molecules could save lives is justified. SN - 1664-3224 UR - https://www.unboundmedicine.com/medline/citation/32754161/Identification_of_SARS_CoV_2_Cell_Entry_Inhibitors_by_Drug_Repurposing_Using_in_silico_Structure_Based_Virtual_Screening_Approach_ L2 - https://doi.org/10.3389/fimmu.2020.01664 DB - PRIME DP - Unbound Medicine ER -