In Silico Evaluation of Prospective Anti-COVID-19 Drug Candidates as Potential SARS-CoV-2 Main Protease Inhibitors

Ibrahim, Mahmoud A. A.; Abdelrahman, Alaa H. M.; Allemailem, Khaled S.; Almatroudi, Ahmad; Moustafa, Mahmoud F.; Hegazy, Mohamed-Elamir F.

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(pro)). 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(pro) 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(pro), 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(pro)'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(pro)'s active site over the 50 ns MD simulation. This study sheds light on HIV protease drugs as prospective SARS-CoV-2 M(pro) inhibitors. [Image: see text] SUPPLEMENTARY INFORMATION: The online version of this article (10.1007/s10930-020-09945-6) contains supplementary material, which is available to authorized users.