Abstract

Introduction: Currently, there are no effective medications for treating all the clinical conditions of patients with COVID-19. We aimed to evaluate the antiviral activity of compounds derived from L-tyrosine against the B.1 lineage of SARS-CoV-2 in vitro and in silico. Methodology: The cytotoxicities of 15 halogenated compounds derived from L-tyrosine were evaluated in Vero-E6 cells by the MTT assay. The antiviral activity of the compounds was evaluated using four strategies, and viral quantification was performed by a plaque assay and qRT-PCR. The toxicity of the compounds was evaluated by ADMET predictor software. The affinity of these compounds for viral or cellular proteins and the stability of their conformations were determined by docking and molecular dynamics, respectively. Results: TODC-3M, TODI-2M, and YODC-3M reduced the viral titer >40% and inhibited the replication of viral RNA without significant cytotoxicity. In silico analyses revealed that these compounds presented low toxicity and binding energies between −4.3 and −5.2 Kcal/mol for three viral proteins (spike, Mpro, and RdRp). TODC-3M and YODC-3M presented the most stable conformations with the evaluated proteins. Conclusions: The most promising compounds were TODC-3M, TODI-2M, and YODC-3M, which presented low in vitro and in silico toxicity, antiviral potential through different strategies, and favorable affinities for viral targets. Therefore, they are candidates for in vivo studies.

By Paula A. Velásquez-Bedoya, María I. Zapata-Cardona, Laura M. Monsalve-Escudero, Jaime A. Pereañez, Diego Guerra-Arias, Manuel Pastrana-Restrepo, Elkin Galeano andWildeman Zapata-Builes