A paper about the discovery of “the first potent and specific anti-COVID-19 drug” has been retracted after it emerged that the compound wasn’t so novel after all.
The article, published in May 2021 in Chemical Papers has been cited seven times, according to Clarivate Analytics’ Web of Science.
As the paper’s sole author, Amgad M. Rabie, writes in the abstract:
I discovered a new favipiravir derivative, (E)-N-(4-cyanobenzylidene)-6-fluoro-3-hydroxypyrazine-2-carboxamide (cyanorona-20), as the first potent SARS-CoV-2 inhibitor with very high selectivity (209- and 45-fold more potent than favipiravir and remdesivir, respectively). … This promising selective anti-COVID-19 compound is also, to the best of our knowledge, the first bioactive derivative of favipiravir, the known antiinfluenza and antiviral drug. This new nucleoside analog was designed, synthesized, characterized, computationally studied (through pharmacokinetic calculations along with computational molecular modeling and prediction), and biologically evaluated for its anti-COVID-19 activities (through a validated in vitro anti-COVID-19 assay). The results of the biological assay showed that cyanorona-20 surprisingly exhibited very significant anti-COVID-19 activity (anti-SARS-CoV-2 EC50 = 0.45 μM), and, in addition, it could be also a very promising lead compound for the design of new anti-COVID-19 agents. Cyanorona-20 is a new favipiravir derivative with promise for the treatment of SARS-CoV-2 infection.
But the “new” molecule apparently wasn’t. According to the retraction notice:
The Editor-in-Chief has retracted this article. After publication, Dr Michal Šoral (Slovak Academy of Sciences) raised concerns with respect to the complete inconsistency of the NMR spectra presented in the Supplementary Information files with the assigned structure of the key compound cyanorona-20 ((E)-N(4-cyanobenzylidene)-6-fluoro-3-hydroxypyrazine-2-carboxamide) in this article. Independent post-publication peer review supported these concerns and verified that there is overlap of the NMR spectra with those in a previously published article (Rabie 2020). In addition, independent efforts to reproduce the synthesis of cyanorona-20 were unsuccessful. The Editor-in-Chief therefore no longer has confidence in the results and conclusions presented. The author does not agree with this retraction.
Šoral happened to notice oddities in the NMR spectra while browsing the journal to learn its style as a peer reviewer, he told us.
I first noticed Rabie’s paper during a peer review of a completely different manuscript for Chemical Papers – I believe I was just randomly browsing the latest issues of the journal for the journal’s style of reference notation. As the COVID-19 topic was hot at that time, I read Rabie’s paper further and, as an NMR spectroscopist, looked at the NMR spectra of the compound. No residual signal of the non-perdeuterated solvent, nor the signal of water were present in the 1H NMR spectrum – this was probably the first hint that the spectra might not be authentic. At that time, Rabie only had a few published papers – I eventually managed to find out that the 1H and 13C NMR spectrum of the compound from the retracted article was most probably artificially constructed in MS Paintbrush (or its equivalent) from the 1H and 13C spectra of galloyl hydrazide from his previous publication (see https://doi.org/10.1016/j.mex.2019.11.010). For the most part, the two pairs of spectra shared the same random noise, peak shapes and even a small portion of identical impurity signals whose position in the 1H spectrum was altered. No special software was used for the detection of the similarity/identity of the random noise patterns.
I also raised these concerns on Pubpeer, but in the thread corresponding to Rabie’s paper in the journal International Immunopharmacology (see https://pubpeer.com/publications/89D458336E6E07405BBD6F551940DF). A part of the paper and the supporting information thereof contains verbatim or rephrased parts of the retracted article, including tables, images and even the 1H and 13C spectra, that played the role in the retraction of the article in Chemical Papers.
I am satisfied with the journal’s response.
Milan Polakovič, editor-in-chief of Chemical Papers, told us, “I have nothing to add besides what was officially reported.”
Rabie’s affiliation is listed on the retracted paper as “Dr. Amgad Rabie’s Research Lab. for Drug Discovery (DARLD), Mansoura, Egypt.”
His LinkedIn profile – replete with superlatives – lists many more jobs, including head of the clinical research department at Dikernis General Hospital in Egypt, senior clinical research associate for the Egyptian Ministry of Health and Population, clinical research associate at Harvard Medical School, and editor-in-chief of five journals. He did not respond to our request for comment.
By our count, the retraction is the 235th of a COVID-19 paper.
Update, 6/8/22, 1430 UTC: Updated with comments from Šoral.
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