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

Development and validation of molnupiravir assessment in bulk powder and pharmaceutical formulation by the RP-HPLC-UV method

“…[5][6][7][8][9][10] Consequently, MOL represents a promising cost-effective cure for the treatment of COVID-19 while demonstrating high safety and efficacy in ongoing clinical trials. [11][12][13][14][15] MOL is considered to be the rst oral, directacting antiviral proved to be extremely efficient at reducing nasopharyngeal SARS-CoV-2 infective virus and viral RNA. [16][17][18][19] The chemical structure of MOL is shown in Fig.…”

Comparative molecular docking and simulation analysis of molnupiravir and remdesivir with SARS-CoV-2 RNA dependent RNA polymerase (RdRp)

“…The lung viral load in animals lowers 25,000 times after oral administration and roughly 100,000 times when given as prophylactic. It stops the virus from spreading and eliminates its presence in the oropharynx [ 11 , 12 ]. In case of human trials, two variants of the virus including Wuhan strain or B.1.1.7 and B.1.351 have been tested with molnupiravir.…”