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Identification of potential SARS-CoV-2 entry inhibitors by targeting the interface region between the spike RBD and human ACE2.
Gurung, Arun Bahadur; Ali, Mohammad Ajmal; Lee, Joongku; Farah, Mohammad Abul; Al-Anazi, Khalid Mashay.
  • Gurung AB; Department of Basic Sciences and Social Sciences, North-Eastern Hill University, Shillong, 793022, Meghalaya, India. Electronic address: arunbgurung@gmail.com.
  • Ali MA; Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia.
  • Lee J; Department of Environment and Forest Resources, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Republic of Korea.
  • Farah MA; Department of Zoology, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia.
  • Al-Anazi KM; Department of Zoology, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia.
J Infect Public Health ; 14(2): 227-237, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-988410
Semantic information from SemMedBD (by NLM)
1. angiotensin converting enzyme 2 PART_OF Homo sapiens
Subject
angiotensin converting enzyme 2
Predicate
PART_OF
Object
Homo sapiens
2. 2019 novel coronavirus CAUSES Communicable Diseases
Subject
2019 novel coronavirus
Predicate
CAUSES
Object
Communicable Diseases
3. angiotensin converting enzyme 2 INTERACTS_WITH Vitronecti
Subject
angiotensin converting enzyme 2
Predicate
INTERACTS_WITH
Object
Vitronecti
4. angiotensin converting enzyme 2 INTERACTS_WITH spike protei
Subject
angiotensin converting enzyme 2
Predicate
INTERACTS_WITH
Object
spike protei
5. angiotensin converting enzyme 2 INTERACTS_WITH Viral Proteins
Subject
angiotensin converting enzyme 2
Predicate
INTERACTS_WITH
Object
Viral Proteins
6. angiotensin converting enzyme 2 PART_OF Homo sapiens
Subject
angiotensin converting enzyme 2
Predicate
PART_OF
Object
Homo sapiens
7. 2019 novel coronavirus CAUSES Communicable Diseases
Subject
2019 novel coronavirus
Predicate
CAUSES
Object
Communicable Diseases
8. angiotensin converting enzyme 2 INTERACTS_WITH Vitronectin, human
Subject
angiotensin converting enzyme 2
Predicate
INTERACTS_WITH
Object
Vitronectin, human
9. angiotensin converting enzyme 2 INTERACTS_WITH spike protein, SARS-CoV-2
Subject
angiotensin converting enzyme 2
Predicate
INTERACTS_WITH
Object
spike protein, SARS-CoV-2
10. angiotensin converting enzyme 2 INTERACTS_WITH Viral Proteins
Subject
angiotensin converting enzyme 2
Predicate
INTERACTS_WITH
Object
Viral Proteins
ABSTRACT
Coronavirus disease 2019 (COVID-19) is a fatal infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The virus infection is initiated upon recognition and binding of the spike (S) protein receptor-binding domain (RBD) to the host cell surface receptor, angiotensin-converting enzyme 2 (ACE2). Blocking the interaction between S protein and ACE2 receptor is a novel approach to prevent the viral entry into the host cell. The present study is aimed at the identification of small molecules which can disrupt the interaction between SARS-CoV-2 S protein and human ACE2 receptor by binding to the interface region. A chemical library consisting of 1,36,191 molecules were screened for drug-like compounds based on Lipinski's rule of five, Verber's rule and in silico toxicity parameters. The filtered drug-like molecules were next subjected to molecular docking in the interface region of RBD. The best three hits viz; ZINC64023823, ZINC33039472 and ZINC00991597 were further taken for molecular dynamics (MD) simulation studies and binding free energy evaluations using Molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) and Molecular mechanics-Generalized Born surface area (MM-GBSA). The protein-ligand complexes showed stable trajectories throughout the simulation time. ZINC33039472 exhibited binding free energy value lower as compared to the control (emodin) with a higher contribution by gas-phase energy and van der Waals energy to the total binding free energy. Thus, ZINC33039472 is identified to be a promising interfacial binding molecule which can inhibit the interaction between the viral S protein and human ACE2 receptor which would consequently help in the management of the disease.
Subject(s)
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Virus Internalization / Spike Glycoprotein, Coronavirus / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 Type of study: Experimental Studies Limits: Humans Language: English Journal: J Infect Public Health Journal subject: Communicable Diseases / Public Health Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Virus Internalization / Spike Glycoprotein, Coronavirus / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 Type of study: Experimental Studies Limits: Humans Language: English Journal: J Infect Public Health Journal subject: Communicable Diseases / Public Health Year: 2021 Document Type: Article