info:eu-repo/semantics/article
In vitro and in silico evaluation of antiretrovirals against SARS-CoV-2: A drug repurposing approach
Registro en:
Zapata-Cardona MI, Florez-Alvarez L, Guerra-Sandoval AL, Chvatal-Medina M, Guerra-Almonacid CM, Hincapie-Garcia J, Hernandez JC, Rugeles MT, Zapata-Builes W. In vitro and in silico evaluation of antiretrovirals against SARS-CoV-2: A drug repurposing approach. AIMS Microbiol. 2023 Jan 16;9(1):20-40. doi: 10.3934/microbiol.2023002. PMID: 36891537; PMCID: PMC9988408.
2471-1888
10.3934/microbiol.2023002
2471-1888
Autor
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
Institución
Resumen
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
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