[Plitidepsin, an inhibitor of the cell elongation factor eEF1a, and molnupiravir an analogue of the ribonucleoside cytidine, two new chemical compounds with intense activity against SARS-CoV-2]

Abstract

The knowledge of the replicative cycle of SARS-CoV-2 and its interactions with cellular proteins has opened a new therapeutic possibility based on blocking those essential for the virus. The cellular protein elongation factor eEF1A could be a good target. Among its natural inhibitors are didemnins and their related chemical compounds such as plitidepsin. In human cell culture, this compound is capable of inhibiting the virus with a potency 27,5 times that of remdesivir. It must be administered intravenously. Of the ribonucleoside analogues, molnupiravir (MK-4483/EIDD-2801) (hydroxy-cytidine) determines a lethal mutagenesis on SARS-CoV-2. In animals, after oral administration, the pulmonary viral load decreases 25,000 times and when administered as prophylaxis, approximately 100,000 times. It prevents the transmission of the virus and eliminates its presence in the oropharynx. Both chemicals have started Phase I / II human clinical trials.

Keywords: SARS-CoV-2 sntiviral; molnupiravir (MK-4482/EIDD-2801); plitidepsin.

Figura 1

Proceso de incorporación de un nuevo triplete (Met-tARN) al ribosoma celular para la elongación de la cadena proteica en la que participa el Factor de Elongación eEF1A (modificado de Brönstrup et al. [6]).

Figura 2

Estructura química de la plitidepsina (dehidrodidemnina B).

Figura 3

Estructura química de molnupiravir o análogo ribonucleósido ß-D-N4-hidroxicitidina (NHC).

Figura 4

Estructura química de molnupiravir con sus dos formas químicas: la oxima semejante a uridina y su tautómera semejante a guanosina (tomado de Al-Horani et al.[17] (CC BY 4.0).