Is the anti-psychotic, 10-(3-(dimethylamino)propyl)phenothiazine (promazine), a potential drug with which to treat SARS infections? Lack of efficacy of promazine on SARS-CoV replication in a mouse model.

Antiviral Research
Dale L BarnardRobert W Sidwell

Abstract

Phenothiazine and derivatives were tested for inhibition of SARS-CoV replication. Phenothiazine slightly inhibited SARS-CoV replication in a neutral red (NR) uptake assay. Adding a propylamino group to give promazine reduced virus yields (VYR assay) with an EC(90)=8.3+/-2.8 microM, but without selectivity. Various substitutions in the basic phenothiazine structure did not promote efficacy. Phenazine ethosulfate was the most potent compound by VYR assay (EC(90)=6.1+/-4.3 microM). All compounds were toxic (IC(50)=6.6-74.5 microM) except for phenoxathiin (IC(50)=858+/-208 microM) and 10-(alpha-diethylamino-propionyl) phenothiazine.HCl (IC(50)=195+/-71.2 microM). Consequently, none were selective inhibitors of SARS-CoV replication (SI values <1-3.3 microM). These data portended the poor efficacy of promazine in a SARS-CoV mouse lung replication model. Intraperitoneal treatment with promazine using a prophylactic (-4h)/therapeutic regimen of 1, 10, or 50mg/(kg day) did not reduce virus lung titers at day 3, yet prolonged virus replication to 14 days. Similar therapeutic promazine doses were not efficacious. Thus, promazine did not affect SARS-CoV replication in vitro or in vivo, nor were any other phenothiazines efficacious in reduc...Continue Reading

References

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Citations

Jul 19, 2011·Future Virology·Dale L Barnard, Yohichi Kumaki
Oct 20, 2020·Frontiers in Immunology·Narasimha M BeerakaGjumrakch Aliev
Mar 2, 2021·Journal of Clinical Pharmacy and Therapeutics·Pascal Le Corre, Gwenolé Loas
Mar 13, 2021·Frontiers in Pharmacology·Catherine Z ChenWei Zheng
Aug 11, 2021·Assay and Drug Development Technologies·Shea R GoldenJulie Blatt
Nov 11, 2021·Future Microbiology·Sarah AherfiDidier Raoult

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Methods Mentioned

BETA
light microscopy

Software Mentioned

jmp
SAS
Quansys

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