ABSTRACT
Before entering the cell, the SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD) binds to the human angiotensin-converting enzyme 2 (hACE2) receptor. Hence, this RBD is a critical target for the development of antiviral agents. Recent studies have discovered that SARS-CoV-2 variants with mutations in the RBD have spread globally. The purpose of this in silico study was to determine the potential of a fruit bromelain-derived peptide. DYGAVNEVK. to inhibit the entry of various SARS-CoV-2 variants into human cells by targeting the hACE binding site within the RBD. Molecular docking analysis revealed that DYGAVNEVK interacts with several critical RBD binding residues responsible for the adhesion of the RBD to hACE2. Moreover, 100 ns MD simulations revealed stable interactions between DYGAVNEVK and RBD variants derived from the trajectory of root-mean-square deviation (RMSD), radius of gyration (Rg), and root-mean-square fluctuation (RMSF) analysis, as well as free binding energy calculations. Overall, our computational results indicate that DYGAVNEVK warrants further investigation as a candidate for preventing SARS-CoV-2 due to its interaction with the RBD of SARS-CoV-2 variants.
Subject(s)
Angiotensin-Converting Enzyme 2 , Bromelains , Computer Simulation , Protein Interaction Domains and Motifs , SARS-CoV-2 , Angiotensin-Converting Enzyme 2/chemistry , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Bromelains/chemistry , Bromelains/pharmacology , Models, Molecular , Molecular Docking Simulation , Molecular Dynamics Simulation , Peptides/chemistry , Peptides/pharmacology , Protein Binding , SARS-CoV-2/chemistry , SARS-CoV-2/drug effects , Spike Glycoprotein, Coronavirus/chemistry , COVID-19 Drug TreatmentABSTRACT
The COVID-19 corona virus has become a world pandemic which started in December 2019 in Wuhan, China with no confirmed biological source. Various countries reported the genomic sequence of different isolates obtained from infected patients. This allowed us to obtain a number of 38 isolates of full genomic sequences. Alignment of nucleotide (nt) sequence was carried out using Clustal Omega multiple alignment service at the EBI website. Alignment of nt sequence and phylogenetic relationship revealed that the COVID-19 is a new viral strain and its biological source has not been yet detected. The expected orf pattern was different among isolates obtained from the same country or different countries as well as from SARS-CoV isolates or bats CoV suggesting different virus human interaction possibilities during infection and severity. All isolates had the main five orfs (1ab, S, M, N, E), whereas they differed in the expected accessory orfs. Being with the biological source of COVID-19 undetected, the role of human endogenous retrovirus (HERVs) in the regulation of the host cell gene expression or the encoding for products that could modulate COVID-19 infection and the spectrum of its symptoms is discussed.