An in-silico study on selected organosulfur compounds as potential drugs for SARS-CoV-2 infection via binding multiple drug targets

Abstract

Graphical abstract

Comparative study of the interaction of ivermectin with proteins of interest associated with SARS-CoV-2: A computational and biophysical approach

“…4 D). There are few reports of DM of ivermectin versus Mpro, however, the results obtained in terms of RMSD of the Cα atoms of M pro in SARS-CoV-2 are related to those reported during the simulation period of 100 ns versus other compounds that also remained in the steady state at ≈ 3 Å RMSD [ 16 , 96 , 97 ].…”

“…The energetic fluctuations over time, specifically at ≈ 30 ns and ≈ 70 ns have already been described and show the variations in the thermodynamic stability of the Helicase system in the presence of ivermectin [ 4 ]. Furthermore, the Helicase values in terms of global RMSD are high due to its large structure, which includes several loops and flexible domains as reported against other types of ligands [ 16 ].…”

“…The host nuclear import system can be bound and sequestered by pathogens such as SARS-CoV-2 allowing transportation of viral proteins to the host nucleus leading to increased viral replication [ [12] , [13] , [14] , [15] ]. Additionally, we also consider the multi-functional helicase (nsp13) of SARS-CoV-2 responsible for viral replication (PDB: 6ZSL ) [ [16] , [17] , [18] ], and the main protease (Mpro) of SARS-CoV-2 (PDB: 6LU7 ) as it is a key enzyme of coronaviruses and has a fundamental role in mediating viral replication and transcription, making it an attractive target for drugs [ 11 , [19] , [20] , [21] , [22] ]. All structures were obtained in PDB format from the RCSB protein database ( https://www.rcsb.org/ ).…”

Structural deformability induced in proteins of potential interest associated with COVID-19 by binding of homologues present in ivermectin: Comparative study based in elastic networks models

“…The host nuclear import system can be bound and sequestered by pathogens such as SARS-CoV-2 allowing transportation of viral proteins to the host nucleus leading to increased viral replication [25] , [26] , [27] , [28] , [29] . Additionally, we also consider the multi-functional helicase (nsp13) of SARS-CoV-2 responsible for viral replication (PDB: 6ZSL) [30] , [31] , [32] , and the main protease (Mpro) of SARS-CoV-2 (PDB: 6LU7) as it is a key enzyme of coronaviruses and has a fundamental role in mediating viral replication and transcription, making it an attractive target for drugs [33] , [34] , [35] , [36] , [37] . All structures were obtained in PDB format from the RCSB Protein Data Bank ( https://www.rcsb.org/ ).…”

Modelling the active SARS-CoV-2 helicase complex as a basis for structure-based inhibitor design

“…Although more attention is directed to targeting the RdRp 22,[25][26][27] or the main protease, [28][29][30][31][32] as these are suggested to be more susceptible for binding an inhibitor, [33][34][35] the helicase is also subject to modelling and docking studies. Crucially, however, the pharmacophore and docking studies of the helicase start from the homologous SARS-CoV crystal structure (Figure 2a) [36][37][38][39][40] or the counterpart in SARS-CoV-2 (Figure 2b), 41 which are both apo, lacking the ATP and the ssRNA from the complex. MD simulations are also available with ATP and ssRNA that used a docking approach to identify promising bound ligands at the ATP binding site.…”