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BMC Pharmacol Toxicol ; 22(1): 61, 2021 10 21.
Artículo en Inglés | MEDLINE | ID: covidwho-1477468

RESUMEN

BACKGROUND: The emergence and rapid spread of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) in thelate 2019 has caused a devastating global pandemic of the severe pneumonia-like disease coronavirus disease 2019 (COVID-19). Although vaccines have been and are being developed, they are not accessible to everyone and not everyone can receive these vaccines. Also, it typically takes more than 10 years until a new therapeutic agent is approved for usage. Therefore, repurposing of known drugs can lend itself well as a key approach for significantly expediting the development of new therapies for COVID-19. METHODS: We have incorporated machine learning-based computational tools and in silico models into the drug discovery process to predict Adsorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiles of 90 potential drugs for COVID-19 treatment identified from two independent studies mainly with the purpose of mitigating late-phase failures because of inferior pharmacokinetics and toxicity. RESULTS: Here, we summarize the cardiotoxicity and general toxicity profiles of 90 potential drugs for COVID-19 treatment and outline the risks of repurposing and propose a stratification of patients accordingly. We shortlist a total of five compounds based on their non-toxic properties. CONCLUSION: In summary, this manuscript aims to provide a potentially useful source of essential knowledge on toxicity assessment of 90 compounds for healthcare practitioners and researchers to find off-label alternatives for the treatment for COVID-19. The majority of the molecules discussed in this manuscript have already moved into clinical trials and thus their known pharmacological and human safety profiles are expected to facilitate a fast track preclinical and clinical assessment for treating COVID-19.


Asunto(s)
Antivirales/toxicidad , Tratamiento Farmacológico de COVID-19 , Descubrimiento de Drogas , Reposicionamiento de Medicamentos , Animales , Antivirales/efectos adversos , Captopril/uso terapéutico , Cardiotoxinas/toxicidad , Catecoles/uso terapéutico , Biología Computacional , Sistema Enzimático del Citocromo P-450/metabolismo , Descubrimiento de Drogas/métodos , Humanos , Indometacina/uso terapéutico , Linezolid/uso terapéutico , Hígado/efectos de los fármacos , Ratones , Modelos Biológicos , Nitrilos/uso terapéutico , Ratas , Reproducción/efectos de los fármacos , Programas Informáticos , Ácido Valproico/uso terapéutico
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