tetano
Editor, Senior Moderator
Protein J
. 2021 Jan 2.
doi: 10.1007/s10930-020-09945-6. Online ahead of print.
In Silico Evaluation of Prospective Anti-COVID-19 Drug Candidates as Potential SARS-CoV-2 Main Protease Inhibitors
Mahmoud A A Ibrahim[SUP] 1 [/SUP], Alaa H M Abdelrahman[SUP] 2 [/SUP], Khaled S Allemailem[SUP] 3 [/SUP], Ahmad Almatroudi[SUP] 3 [/SUP], Mahmoud F Moustafa[SUP] 4 5 [/SUP], Mohamed-Elamir F Hegazy[SUP] 6 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently emanating human infectious coronavirus that causes COVID-19 disease. On 11th March 2020, it has been announced as a pandemic by the World Health Organization (WHO). Recently, several repositioned drugs have been subjected to clinical investigations as anti-COVID-19 drugs. Here, in silico drug discovery tools were utilized to evaluate the binding affinities and features of eighteen anti-COVID-19 drug candidates against SARS-CoV-2 main protease (M[SUP]pro[/SUP]). Molecular docking calculations using Autodock Vina showed considerable binding affinities of the investigated drugs with docking scores ranging from - 5.3 to - 8.3 kcal/mol, with higher binding affinities for HIV drugs compared to the other antiviral drugs. Molecular dynamics (MD) simulations were performed for the predicted drug-M[SUP]pro[/SUP] complexes for 50 ns, followed by binding energy calculations utilizing molecular mechanics-generalized Born surface area (MM-GBSA) approach. MM-GBSA calculations demonstrated promising binding affinities of TMC-310911 and ritonavir towards SARS-CoV-2 M[SUP]pro[/SUP], with binding energy values of - 52.8 and - 49.4 kcal/mol, respectively. Surpass potentialities of TMC-310911 and ritonavir are returned to their capabilities of forming multiple hydrogen bonds with the proximal amino acids inside M[SUP]pro[/SUP]'s binding site. Structural and energetic analyses involving root-mean-square deviation, binding energy per-frame, center-of-mass distance, and hydrogen bond length demonstrated the stability of TMC-310911 and ritonavir inside the M[SUP]pro[/SUP]'s active site over the 50 ns MD simulation. This study sheds light on HIV protease drugs as prospective SARS-CoV-2 M[SUP]pro[/SUP] inhibitors.
Keywords: COVID-19; Molecular docking; Molecular dynamics; Repositioned drugs; SARS-CoV-2 main protease.
. 2021 Jan 2.
doi: 10.1007/s10930-020-09945-6. Online ahead of print.
In Silico Evaluation of Prospective Anti-COVID-19 Drug Candidates as Potential SARS-CoV-2 Main Protease Inhibitors
Mahmoud A A Ibrahim[SUP] 1 [/SUP], Alaa H M Abdelrahman[SUP] 2 [/SUP], Khaled S Allemailem[SUP] 3 [/SUP], Ahmad Almatroudi[SUP] 3 [/SUP], Mahmoud F Moustafa[SUP] 4 5 [/SUP], Mohamed-Elamir F Hegazy[SUP] 6 [/SUP]
Affiliations
- PMID: 33387249
- DOI: 10.1007/s10930-020-09945-6
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently emanating human infectious coronavirus that causes COVID-19 disease. On 11th March 2020, it has been announced as a pandemic by the World Health Organization (WHO). Recently, several repositioned drugs have been subjected to clinical investigations as anti-COVID-19 drugs. Here, in silico drug discovery tools were utilized to evaluate the binding affinities and features of eighteen anti-COVID-19 drug candidates against SARS-CoV-2 main protease (M[SUP]pro[/SUP]). Molecular docking calculations using Autodock Vina showed considerable binding affinities of the investigated drugs with docking scores ranging from - 5.3 to - 8.3 kcal/mol, with higher binding affinities for HIV drugs compared to the other antiviral drugs. Molecular dynamics (MD) simulations were performed for the predicted drug-M[SUP]pro[/SUP] complexes for 50 ns, followed by binding energy calculations utilizing molecular mechanics-generalized Born surface area (MM-GBSA) approach. MM-GBSA calculations demonstrated promising binding affinities of TMC-310911 and ritonavir towards SARS-CoV-2 M[SUP]pro[/SUP], with binding energy values of - 52.8 and - 49.4 kcal/mol, respectively. Surpass potentialities of TMC-310911 and ritonavir are returned to their capabilities of forming multiple hydrogen bonds with the proximal amino acids inside M[SUP]pro[/SUP]'s binding site. Structural and energetic analyses involving root-mean-square deviation, binding energy per-frame, center-of-mass distance, and hydrogen bond length demonstrated the stability of TMC-310911 and ritonavir inside the M[SUP]pro[/SUP]'s active site over the 50 ns MD simulation. This study sheds light on HIV protease drugs as prospective SARS-CoV-2 M[SUP]pro[/SUP] inhibitors.
Keywords: COVID-19; Molecular docking; Molecular dynamics; Repositioned drugs; SARS-CoV-2 main protease.