Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus , Coronavirus Infections/drug therapy , Hydroxychloroquine/therapeutic use , Models, Biological , Pneumonia, Viral/drug therapy , Animals , Betacoronavirus/drug effects , Betacoronavirus/pathogenicity , COVID-19 , Cricetinae , Humans , Mice , Pandemics , Primates , SARS-CoV-2 , Treatment Failure , COVID-19 Drug TreatmentABSTRACT
We here report on the activity of 2'-C-methylcytidine (2CMC) [a nucleoside polymerase inhibitor of the hepatitis C virus (HCV)] on the in vitro replication of (murine) norovirus (MNV). 2CMC inhibits (i) virus-induced CPE formation, (ii) viral RNA synthesis and (iii) infectious progeny formation with EC(50) values of â¼2µM. 2CMC acts at a time-point that coincides with the onset of viral RNA synthesis. Even following 30 passages of selective pressure no MNV-resistant virus was selected, which is in line with the high barrier to resistance of the nucleoside analogue for HCV. When combined with the broad-spectrum RNA virus inhibitor ribavirin, a marked antagonistic activity was observed indicating that these molecules should not be combined for the treatment of norovirus infections. Our results suggest that 2'-C-methyl nucleoside analogues should be further explored for the treatment and prophylaxis of norovirus infections.
Subject(s)
Antiviral Agents/pharmacology , Cytidine/analogs & derivatives , Norovirus/drug effects , Virus Replication/drug effects , Animals , Cell Line , Cytidine/pharmacology , Drug Resistance, Viral/genetics , Mice , Norovirus/genetics , Norovirus/physiology , Ribavirin/pharmacologyABSTRACT
Human noroviruses are the primary cause of foodborne gastroenteritis. Potent and safe inhibitors are needed for the treatment/prophylaxis of norovirus infections. We demonstrate that Favipiravir [T-705, a drug in advanced clinical development for the treatment of infections with the influenza virus] inhibits in vitro murine norovirus replication. Time-of-drug addition studies reveal that T-705 exerts its activity at a time-point that coincides with onset of viral RNA synthesis, which is in line with the viral polymerase as the presumed target.
Subject(s)
Amides/pharmacology , Norovirus/drug effects , Pyrazines/pharmacology , Virus Replication/drug effects , Animals , Cell Line , Mice , RNA, Viral/antagonists & inhibitors , RNA, Viral/biosynthesisABSTRACT
The in vivo administration of 59Fe to the rat accompanied by acetylsalicylic acid (ASA) enhanced significantly counts in blood, spleen, liver and femur without affecting those of the intestine. The results suggest that ASA augments iron absorption either via an inhibitory action on the synthesis of prostaglandins or by a purely chemical mechanism.
Subject(s)
Aspirin/pharmacology , Intestinal Absorption/drug effects , Iron/metabolism , Animals , Bone and Bones/metabolism , Intestinal Mucosa/metabolism , Liver/metabolism , Male , Organ Specificity , Rats , Spleen/metabolismABSTRACT
Nine newly synthesized eugenol derivatives were investigated in rats or mice as to their anesthetic, hypothermic, myorelaxant and anticonvulsant effects. Additional pharmacological activity which appeared during the experiments is described. For comparative purposes, six naturally occurring eugenol analogues were included in the study. The results are further discussed as to possible structure-activity relationships between the test compounds and the four investigated effects.
