In Silico Identification of Potential Inhibitors of SARS-CoV-2 Main Protease (M pro )

• Published in: Pathogens (Basel) Vol. 13; no. 10; p. 887
• Main Authors: Hernández-Serda, Manuel Alejandro, Vázquez-Valadez, Víctor H, Aguirre-Vidal, Pablo, Markarian, Nathan M, Medina-Franco, José L, Cardenas-Granados, Luis Alfonso, Alarcón-López, Aldo Yoshio, Martínez-Soriano, Pablo A, Velázquez-Sánchez, Ana María, Falfán-Valencia, Rodolfo E, Angeles, Enrique, Abrahamyan, Levon
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 11.10.2024; MDPI
• Subjects: 3CLpro; Antiviral agents; Antiviral drugs; antivirals; Atazanavir; Binding sites; Canada; Chemical compounds; Chemical synthesis; Coronaviruses; Cost effectiveness; COVID-19; Drug development; Dynamic structural analysis; Epidemics; Genomes; Global health; Health aspects; Ligands; Mexico; Middle East respiratory syndrome; Molecular dynamics; Mpro; Mutation; Nsp5; Pandemics; Protease inhibitors; Proteinase inhibitors; Proteins; R&D; Research & development; RNA polymerase; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Structure-activity relationships; Vaccines; Viral diseases; Canada; Mexico; antivirals; SARS-CoV-2; 3CLpro; Mpro; Nsp5
• ISSN: 2076-0817; 2076-0817
• DOI: 10.3390/pathogens13100887

The ongoing Coronavirus Disease 19 (COVID-19) pandemic has had a profound impact on the global healthcare system. As the SARS-CoV-2 virus, responsible for this pandemic, continues to spread and develop mutations in its genetic material, new variants of interest (VOIs) and variants of concern (VOCs) are emerging. These outbreaks lead to a decrease in the efficacy of existing treatments such as vaccines or drugs, highlighting the urgency of new therapies for COVID-19. Therefore, in this study, we aimed to identify potential SARS-CoV-2 antivirals using a virtual screening protocol and molecular dynamics simulations. These techniques allowed us to predict the binding affinity of a database of compounds with the virus M protein. This in silico approach enabled us to identify twenty-two chemical structures from a public database (QSAR Toolbox Ver 4.5 ) and ten promising molecules from our in-house database. The latter molecules possess advantageous qualities, such as two-step synthesis, cost-effectiveness, and long-lasting physical and chemical stability. Consequently, these molecules can be considered as promising alternatives to combat emerging SARS-CoV-2 variants.