Repositioning Adequate Antibiotics to Treat/Cure the Coronavirus Disease 2019 (COVID-19): Current Treatments and Future Directions
(2021) The Open Biochemistry Journal — Vol. 15, n° 1, p. 1-19 (2021)
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- AIMS: Rational use of antibiotics against the betacoronavirus SARS-CoV-2 responsible for the COVID-19 pandemic. OBJECTIVE : Repositioning and repurposing adequate antibiotics to cure the Coronavirus Disease 2019 (COVID-19). BACKGROUND : It is widely accepted that viral infections such as the SARS-CoV-2 cannot be cured by antibiotics, whereas bacterial infections can. It is because the SARS-CoV-2 virus has no protein synthesis machinery (usually targeted by antibiotics) to produce from its RNA genome, the viral proteins and enzymes essential for its replication and/or for the assembly of viral particles. However, the antibiotics must be capable of inhibiting the ribosomes of the protein synthesis machinery of the SARS-CoV-2-infected human host cells, in order to prevent them from synthesizing new proteins that they do not need, but are needed for the virus to spread. Unfortunately, the only antibiotic capable of selectively inhibiting the human 80S ribosomes, namely cycloheximide, was found to be a poisonous drug for the mammals. Therefore, the only possibility is to search for the antibiotics that are capable of inhibiting both bacterial and eukaryal ribosomes, in order to prevent at the same time the ribosomes of the infected human host cells from synthesizing the proteins and enzymes for the SARS-CoV-2 virus, and those of the eventual opportunistic pathogenic bacteria from developing pneumonia. METHODS: First, we have used a molecular modeling study involving the tools of the semi-empirical quantum mechanics PM3 method to study the interaction between the cation Zn++ and all the molecules considered as zinc transporters in this report. By this approach, the niche in which Zn++ is located was determined. Such an interaction serves as a shuttle and allows zinc cation to invade endocellular structures in the SARS-CoV-2-infected human host cells. Second, we have measured the poly (U)-dependent poly (Phe) synthesis activity of human 80S ribosomes in the presence of increasing concentrations of four antibiotics of the class of the macrolides, namely erythromycin, azithromycin, clarithromycin and telithromycin. This experiment led us to determine for each macrolide, the half-inhibitory concentration (IC50) that is the concentration of antibiotic corresponding to 50% inhibition of the activity of the human 80S ribosomes. Finally, we have analyzed previously published data from the group of Nierhaus (Berlin) on the competition between the incoming aminoacyl-tRNA and the antibiotic tetracycline for the binding to the ribosomal A-site on the E. coli 70S or rabbit liver 80S ribosomes. This led to the conclusion by the authors that tetracycline most likely binds to corresponding sites in 70S and 80S ribosomes with comparable affinity. [...]
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Hountondji, C., Besnaïnou, G., Gaudet, E., & Poupaert, J. (2021). Repositioning Adequate Antibiotics to Treat/Cure the Coronavirus Disease 2019 (COVID-19): Current Treatments and Future Directions. The Open Biochemistry Journal, 15(1), 1-19. https://doi.org/10.2174/1874091x02115010001 (Original work published 2021)