QSAR Modeling of SARS‐CoV M^pro Inhibitors Identifies Sufugolix, Cenicriviroc, Proglumetacin, and other Drugs as Candidates for Repurposing against SARS‐CoV‐2

Q4 · MEDICINE

Article

Author: Korn, Daniel ; Bobrowski, Tesia ; Schmitt, Charles ; Tropsha, Alexander ; Melo‐Filho, Cleber C. ; Auerbach, Scott ; Muratov, Eugene N. ; Alves, Vinicius M.

AbstractThe main protease (Mpro) of the SARS‐CoV‐2 has been proposed as one of the major drug targets for COVID‐19. We have identified the experimental data on the inhibitory activity of compounds tested against the closely related (96 % sequence identity, 100 % active site conservation) Mpro of SARS‐CoV. We developed QSAR models of these inhibitors and employed these models for virtual screening of all drugs in the DrugBank database. Similarity searching and molecular docking were explored in parallel, but docking failed to correctly discriminate between experimentally active and inactive compounds, so it was not relied upon for prospective virtual screening. Forty‐two compounds were identified by our models as consensus computational hits. Subsequent to our computational studies, NCATS reported the results of experimental screening of their drug collection in SARS‐CoV‐2 cytopathic effect assay (https://opendata-ncats-nih-gov.libproxy1.nus.edu.sg/covid19/). Coincidentally, NCATS tested 11 of our 42 hits, and three of them, cenicriviroc (AC50 of 8.9 μM), proglumetacin (tested twice independently, with AC50 of 8.9 μM and 12.5 μM), and sufugolix (AC50 12.6 μM), were shown to be active. These observations support the value of our modeling approaches and models for guiding the experimental investigations of putative anti‐COVID‐19 drug candidates. All data and models used in this study are publicly available via Supplementary Materials, GitHub (https://github.com/alvesvm/sars‐cov‐mpro), and Chembench web portal (https://chembench.mml.unc.edu/).

01 Jul 1992·The Journal of rheumatology

Possible mechanisms of gastroduodenal mucosal damage in volunteers treated with nonsteroidal antiinflammatory drugs--the usefulness of prodrugs.

Article

Author: Nakagawa, T ; Mizushima, Y ; Endo, T ; Yanagawa, A ; Fukumura, T ; Uemura, H ; Matsui, H

A controlled double blind study on the incidence of nonsteroidal antiinflammatory drug (NSAID) gastropathy was performed in 29 healthy volunteers administered diclofenac Na (10 subjects) or a prodrug (loxoprofen Na in 10 subjects and proglumetacin maleate in 9 subjects). The incidence of NSAID gastropathy was significantly lower in the subjects administered the prodrugs than in those administered diclofenac Na (p less than 0.05), which suggested the clinical usefulness of the prodrugs.

01 May 1992·Revista clinica espanola

[An adverse reaction to proglumetacin].

Letter

Author: Vives, R ; Soria, F J ; Luna, A ; Villarreal, O

100 Deals associated with Proglumetacin Maleate

External Link

KEGG	Wiki	ATC	Drug Bank
D01765	Proglumetacin Maleate	M01AB14	DB13527

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Inflammation	JP	Taiho Pharmaceutical Co., Ltd.	30 Nov 1993
Pain	JP	Taiho Pharmaceutical Co., Ltd.	30 Nov 1993

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