| Title : In vitro enzymatic and cell culture assays for SARS-CoV-2 main protease interaction with ambenonium - de Souza_2025_Sci.Rep_15_10606 |
| Author(s) : de Souza J , de Souza Gomes I , de Souza Fernandes L , Andrade LAF , De Souza L , de Almeida Paiva V , Araujo SC , de Lima LHF , Dias RS , de Melo-Minardi RC , da Fonseca FG , de Paula SO , de Azevedo Silveira S |
| Ref : Sci Rep , 15 :10606 , 2025 |
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Abstract :
The 2019 pandemic of coronavirus disease (COVID-19) caused by SARS-CoV-2 led to millions of deaths worldwide since its emergence. The viral genomic material can code structural and non-structural proteins including the main protease or 3CL(pro), a cysteine protease that cleavages the viral polyprotein generating 11 proteins that participate in viral pre-replication. Thus, 3CL(pro) is a promising therapeutic target for SARS-CoV-2 inhibition by new drugs or drug repositioning because 3CL(pro) is dissimilar to human proteases. We conducted in vitro assays demonstrating the modulation activity of ambenonium, a drug already used in Myasthenia gravis that acts by inhibiting the action of acetylcholinesterase, and had its potential inhibitory activity against viral replication pointed out in a previous in silico study. In concentrations of 100 microM, 50 microM, 25 microM, 10 microM, and 1 microM there was no inhibition in the formation of lysis plates, with a slight increase in the genome copy number at the higher concentrations evaluated. However, in the concentrations of 0,1 microM and 0,01 microM, there was a reduction in the number of lysis plates. This behavior suggests that the ambenonium acts as a modulator of viral activity in vitro. To investigate potential conformational changes in the protein between dimeric and monomeric forms in the presence of the compound, a local docking analysis was performed. Results indicated this conformational shift is possible, though further studies are needed to confirm these findings. |
| PubMedSearch : de Souza_2025_Sci.Rep_15_10606 |
| PubMedID: 40148508 |
de Souza J, de Souza Gomes I, de Souza Fernandes L, Andrade LAF, De Souza L, de Almeida Paiva V, Araujo SC, de Lima LHF, Dias RS, de Melo-Minardi RC, da Fonseca FG, de Paula SO, de Azevedo Silveira S (2025)
In vitro enzymatic and cell culture assays for SARS-CoV-2 main protease interaction with ambenonium
Sci Rep
15 :10606
de Souza J, de Souza Gomes I, de Souza Fernandes L, Andrade LAF, De Souza L, de Almeida Paiva V, Araujo SC, de Lima LHF, Dias RS, de Melo-Minardi RC, da Fonseca FG, de Paula SO, de Azevedo Silveira S (2025)
Sci Rep
15 :10606