In vitro and in silico evaluation of antiretrovirals against SARS-CoV-2: A drug repurposing approach

Abstract: Background: Drug repurposing is a valuable strategy for rapidly developing drugs for treating COVID-19. This study aimed to evaluate the antiviral effect of six antiretrovirals against SARS-CoV-2 in vitro and in silico. Methods: The cytotoxicity of lamivudine, emtricitabine, tenofovir, abacavir, efavirenz and raltegravir on Vero E6 was evaluated by MTT assay. The antiviral activity of each of these compounds was evaluated via a pre-post treatment strategy. The reduction in the viral titer was assessed by plaque assay. In addition, the affinities of the antiretroviral interaction with viral targets RdRp (RNA-dependent RNA polymerase), ExoN-NSP10 (exoribonuclease and its cofactor, the non-structural protein 10) complex and 3CLpro (3-chymotrypsin-like cysteine protease) were evaluated by molecular docking. Results: Lamivudine exhibited antiviral activity against SARS-CoV-2 at 200 µM (58.3%) and 100 µM (66.7%), while emtricitabine showed anti-SARS-CoV-2 activity at 100 µM (59.6%), 50 µM (43.4%) and 25 µM (33.3%). Raltegravir inhibited SARS-CoV-2 at 25, 12.5 and 6.3 µM (43.3%, 39.9% and 38.2%, respectively). The interaction between the antiretrovirals and SARS-CoV-2 RdRp, ExoN-NSP10 and 3CLpro yielded favorable binding energies (from −4.9 kcal/mol to −7.7 kcal/mol) using bioinformatics methods. Conclusion: Lamivudine, emtricitabine and raltegravir showed in vitro antiviral effects against the D614G strain of SARS-CoV-2. Raltegravir was the compound with the greatest in vitro antiviral potential at low concentrations, and it showed the highest binding affinities with crucial SARS-CoV-2 proteins during the viral replication cycle. However, further studies on the therapeutic utility of raltegravir in patients with COVID-19 are required

• Autores: Zapata Cardona, María Isabel; Flórez Álvarez, Lizdany; Guerra Sandoval, Ariadna Lucia; Medina Chvatal, Mateo; Guerra Almonacid, Carlos Martín; Hincapié García, Jaime Alejandro; Hernández López, Juan Carlos; Rugeles López, María Teresa; Zapata Builes, Wildeman
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2023
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/35476
• Acceso en línea: https://hdl.handle.net/10495/35476
• Palabra clave: SARS-CoV-2; Antirretrovirales; Anti-Retroviral Agents; Tratamiento Farmacológico de COVID-19; COVID-19 Drug Treatment; Simulación del Acoplamiento Molecular; Molecular Docking Simulation; Reposicionamiento de Medicamentos; Drug Repositioning; Enfermedades Transmisibles; Communicable Diseases
• Rights: openAccess
• License: http://creativecommons.org/licenses/by/2.5/co/