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. 2020 Oct:177:50-52.
doi: 10.1016/j.biochi.2020.08.006. Epub 2020 Aug 14.

Various interferon (IFN)-inducible transmembrane (IFITM) proteins for COVID-19, is there a role for the combination of mycophenolic acid and interferon?

Razieh Dowran  1 , Seyed Fazel Nabavi  2 , Solomon Habtemariam  3 , Maciej Banach  4 , Shiva Shahmohamadnejad  5 , Cosmin Andrei Cismaru  6 , Ioana Berindan-Neagoe  7 , Adeleh Sahebnasagh  8 , Seyed Mohammad Nabavi  9
Affiliations

Various interferon (IFN)-inducible transmembrane (IFITM) proteins for COVID-19, is there a role for the combination of mycophenolic acid and interferon?

Razieh Dowran et al. Biochimie. 2020 Oct.

Abstract

Various interferon (IFN)-inducible transmembrane (IFITM) proteins are known to be expressed in human tissues though only IFITM 1-3 are inducible by IFN. Numerous studies have shown that activation of IFITM3 could suppress infection by influenza and coronaviruses such as the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). In view of the potential application of IFITM proteins' induction to target SARS-CoV-2 infection that causes COVID-19, this article layout insights into the known antiviral mechanisms and therapeutic agents related to IFITM. Blocking viral entry through various mechanisms and the potential application of the FDA approved immunosuppressant agent, mycophenolic acid, as inducer of IFITM3 are among those discussed.

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Conflict of interest statement

Declaration of competing interest This statement is to certify that all Authors have seen and approved the manuscript being submitted, and agree to the submission to BIOCHIMIE. We warrant that the article is the Authors' original work. We warrant that the article has not received prior publication, is not under consideration for publication elsewhere, and will not be submitted for publication elsewhere, in whole or in part, while under consideration for publication in BIOCHIMIE. On behalf of all Co-Authors, the corresponding Author shall bear full responsibility for the submission. We attest to the fact that all Authors listed on the title page have contributed significantly to the work, have read the manuscript, attest to the validity and legitimacy of the data and their interpretation, and agree to its submission to BIOCHIMIE. We further attest that no other person has fulfilled the requirements for authorship as stated in the Elsevier Authorship-factsheet (2017_ETHICS_AUTH02 - attached), but is not included in the list of authors, and that no other person has contributed substantially to the writing of the manuscript but is not included either among the authors or in the acknowledgements. All authors agree that no modification to the author list can be made without the written acceptance of all authors and the formal approval of the Editor-in-Chief. All authors accept that the Editor-in-Chief's decisions over acceptance or rejection or in the event of any breach of the Principles of Ethical Publishing in BIOCHIMIE being discovered, of retraction are final.

Figures

Fig. 1
Fig. 1
Structures of mycophenolic acid and mycophenolate mofetil.
Fig. 2
Fig. 2
Schematic representation of the potential implications of IFITM proteins in inhibiting SARS-CoV-2 entry at distinct stages of host cell trafficking. SARS-CoV-2 exploits host cells by entry through an endosomal or a non-endosomal pathway as seen in most enveloped viruses, and replicating in newly induced double membrane vesicles (DMVs) shielded from host immune responses, as a characteristic of the coronavirus family. After binding to the ACE2 receptor, an activation of the S protein by pH dependent or pH independent proteases (serine and cysteine-like) is required for an efficient fusion. IFITM1 is expressed mainly at the plasma membrane level, while IFITM3 is mainly intracellular being integrated in the membranes of the endosomal compartments. IFTIM genes overexpression and proteins can act as cellular inhibitors of the early phases of the viral infectious cycle such as the entry and the fusion steps. (Adapted after Smith et al. [18]).
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