molnupiravir and plitidepsin

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.

Topics: Animals; Antiviral Agents; COVID-19; Cytidine; Depsipeptides; Humans; Hydroxylamines; Peptide Elongation Factors; Peptides, Cyclic; Ribonucleosides; SARS-CoV-2

Topics: Adenosine Monophosphate; Administration, Oral; Alanine; Animals; Anti-Inflammatory Agents; Antibodies, Monoclonal; Antibodies, Neutralizing; Antiviral Agents; Clinical Trials as Topic; COVID-19; COVID-19 Drug Treatment; COVID-19 Vaccines; Cytidine; Depsipeptides; Dexamethasone; Drug Combinations; Drug Repositioning; Drug Synergism; Esters; Guanidines; Hospitalization; Host-Pathogen Interactions; Humans; Hydroxylamines; Internationality; Lactams; Leucine; Mice; National Institutes of Health (U.S.); Nitriles; Peptide Elongation Factor 1; Peptides, Cyclic; Proline; Protease Inhibitors; Ritonavir; RNA-Dependent RNA Polymerase; SARS-CoV-2; Serine Endopeptidases; Sodium-Glucose Transporter 2 Inhibitors; United States; Virus Replication