In vitro and in silico evaluation of antiretrovirals against SARS-CoV-2: A drug repurposing approach
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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
AIMS Press
2023-01-01
|
| Series: | AIMS Microbiology |
| Subjects: | |
| Online Access: | https://www.aimspress.com/article/doi/10.3934/microbiol.2023002?viewType=HTML |
| _version_ | 1811159023910649856 |
|---|---|
| author | Maria I. Zapata-Cardona Lizdany Florez-Alvarez Ariadna L. Guerra-Sandoval Mateo Chvatal-Medina Carlos M. Guerra-Almonacid Jaime Hincapie-Garcia Juan C. Hernandez Maria T. Rugeles Wildeman Zapata-Builes |
| author_facet | Maria I. Zapata-Cardona Lizdany Florez-Alvarez Ariadna L. Guerra-Sandoval Mateo Chvatal-Medina Carlos M. Guerra-Almonacid Jaime Hincapie-Garcia Juan C. Hernandez Maria T. Rugeles Wildeman Zapata-Builes |
| author_sort | Maria I. Zapata-Cardona |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T05:33:01Z |
| format | Article |
| id | doaj.art-0638fc4e7acc4b158a2372696f49d638 |
| institution | Directory Open Access Journal |
| issn | 2471-1888 |
| language | English |
| last_indexed | 2024-04-10T05:33:01Z |
| publishDate | 2023-01-01 |
| publisher | AIMS Press |
| record_format | Article |
| series | AIMS Microbiology |
| spelling | doaj.art-0638fc4e7acc4b158a2372696f49d6382023-03-07T01:06:42ZengAIMS PressAIMS Microbiology2471-18882023-01-0191204010.3934/microbiol.2023002In vitro and in silico evaluation of antiretrovirals against SARS-CoV-2: A drug repurposing approachMaria I. Zapata-Cardona 0Lizdany Florez-Alvarez 1Ariadna L. Guerra-Sandoval2Mateo Chvatal-Medina3Carlos M. Guerra-Almonacid4Jaime Hincapie-Garcia5Juan C. Hernandez6Maria T. Rugeles7Wildeman Zapata-Builes 81. Grupo Inmunovirologia, Facultad de Medicina, Universidad de Antioquia UdeA, Medellin, Colombia1. Grupo Inmunovirologia, Facultad de Medicina, Universidad de Antioquia UdeA, Medellin, Colombia 2. Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil3. Grupo de investigacion GIRYSOUT, Universidad del Tolima, Ibague, Colombia1. Grupo Inmunovirologia, Facultad de Medicina, Universidad de Antioquia UdeA, Medellin, Colombia3. Grupo de investigacion GIRYSOUT, Universidad del Tolima, Ibague, Colombia4. Grupo de investigacion, Promocion y prevencion farmaceutica, Facultad de ciencias farmaceuticas yalimentarias, Universidad de Antioquia UdeA, Medellin, Colombia5. Grupo Infettare, Facultad de Medicina, Universidad Cooperativa de Colombia, Medellin, Colombia1. Grupo Inmunovirologia, Facultad de Medicina, Universidad de Antioquia UdeA, Medellin, Colombia1. Grupo Inmunovirologia, Facultad de Medicina, Universidad de Antioquia UdeA, Medellin, Colombia5. Grupo Infettare, Facultad de Medicina, Universidad Cooperativa de Colombia, Medellin, ColombiaBackground: 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.https://www.aimspress.com/article/doi/10.3934/microbiol.2023002?viewType=HTMLantiretroviralssars-cov-2covid-19molecular dockingdrug repurposing |
| spellingShingle | Maria I. Zapata-Cardona Lizdany Florez-Alvarez Ariadna L. Guerra-Sandoval Mateo Chvatal-Medina Carlos M. Guerra-Almonacid Jaime Hincapie-Garcia Juan C. Hernandez Maria T. Rugeles Wildeman Zapata-Builes In vitro and in silico evaluation of antiretrovirals against SARS-CoV-2: A drug repurposing approach AIMS Microbiology antiretrovirals sars-cov-2 covid-19 molecular docking drug repurposing |
| title | In vitro and in silico evaluation of antiretrovirals against SARS-CoV-2: A drug repurposing approach |
| title_full | In vitro and in silico evaluation of antiretrovirals against SARS-CoV-2: A drug repurposing approach |
| title_fullStr | In vitro and in silico evaluation of antiretrovirals against SARS-CoV-2: A drug repurposing approach |
| title_full_unstemmed | In vitro and in silico evaluation of antiretrovirals against SARS-CoV-2: A drug repurposing approach |
| title_short | In vitro and in silico evaluation of antiretrovirals against SARS-CoV-2: A drug repurposing approach |
| title_sort | in vitro and in silico evaluation of antiretrovirals against sars cov 2 a drug repurposing approach |
| topic | antiretrovirals sars-cov-2 covid-19 molecular docking drug repurposing |
| url | https://www.aimspress.com/article/doi/10.3934/microbiol.2023002?viewType=HTML |
| work_keys_str_mv | AT mariaizapatacardona invitroandinsilicoevaluationofantiretroviralsagainstsarscov2adrugrepurposingapproach AT lizdanyflorezalvarez invitroandinsilicoevaluationofantiretroviralsagainstsarscov2adrugrepurposingapproach AT ariadnalguerrasandoval invitroandinsilicoevaluationofantiretroviralsagainstsarscov2adrugrepurposingapproach AT mateochvatalmedina invitroandinsilicoevaluationofantiretroviralsagainstsarscov2adrugrepurposingapproach AT carlosmguerraalmonacid invitroandinsilicoevaluationofantiretroviralsagainstsarscov2adrugrepurposingapproach AT jaimehincapiegarcia invitroandinsilicoevaluationofantiretroviralsagainstsarscov2adrugrepurposingapproach AT juanchernandez invitroandinsilicoevaluationofantiretroviralsagainstsarscov2adrugrepurposingapproach AT mariatrugeles invitroandinsilicoevaluationofantiretroviralsagainstsarscov2adrugrepurposingapproach AT wildemanzapatabuiles invitroandinsilicoevaluationofantiretroviralsagainstsarscov2adrugrepurposingapproach |