In silico screening of FDA approved drugs against ACE2 receptor: potential therapeutics to inhibit the entry of SARS-CoV-2 to human cells. Issue 21 (5th December 2022)

• Record Type: Journal Article
• Authors: Ayyamperumal, Selvaraj; Jade, Dhananjay; Tallapaneni, Vyshnavi; Chandrasekar, M. J. N.; Nanjan, M. J.
• Is Part Of: Journal of biomolecular structure & dynamics. Volume 40:Issue 21(2022)
• Page Start: 11383
• Page End: 11394
• Publication Date: 2022-12-05
• Subjects: COVID-19 -- SARS-CoV-2 -- ACE2 -- drugs repositioning -- virus entry inhibitors; Biomolecules -- Periodicals; Molecular structure -- Periodicals; Molecular Biology -- Periodicals; Biomechanics -- Periodicals; 572
• DOI: 10.1080/07391102.2021.1960892
• Languages: English
• ISSNs: 0739-1102

Abstract

Abstract: An unknown coronavirus that emerged sometime at the end of 2019 in China, the novel SARS-CoV-2, now called COVID-19, has spread all over the world. Several efforts have been made to prevent or treat this disease, though not with success. The initiation of COVID-19 viral infection involves specific binding of SARS-CoV-2 to the host surface of the receptor, ACE2. The ACE2- SARS-CoV-2 complex then gets transferred into the endosomes where the endosomal acidic proteases cleave the S protein present in SARS-CoV-2, activating its fusion and release of the viral genome. We have carried out detailed and thorough in silico studies to repurpose FDA approved compounds to inhibit human ACE2 receptor so as to prevent the viral entry. Our study reveals that five compounds show good binding to the ACE2 receptor and hence are potential candidates to interact with ACE2 and prevent it's recognition by the virus, SARS-CoV-2. Communicated by Ramaswamy H. Sarma Abstract : UF0001 Highlights: Virtual screening of FDA drugs against ACE2 receptor. FDA drugs subjected to space filtering using Ro3 & Ro5 and ADMET. FDA drugs screened through molecular docking methods. Five virtual hit compounds remain stable with less fluctuations. MD simulation and MM-PBSA free energy calculation show that the five hit compounds. Bind to the active pocket with good binding efficiency.