ABSTRACT
In this work we report structural and computational studies of favipiravir, which is now used as a drug for COVID-19 treatment. The molecule is completely flat and stabilized by an intramolecular O–H···O hydrogen bond, yielding a six-membered pseudo-aromatic ring. The aromaticity index of this pseudo-aromatic ring was found to be 0.748, while the same indix for the pyrazine ring in favipiravir was found to be 0.954. The crystal packing of favipiravir is mainly constructed through intermolecular N–H···O, N–H···N and C–H···O hydrogen bonds, yielding a 3D supramolecular framework with a zst topology defined by the point symbol of (65·8). The crystal structure of favipiravir is further stabilized by weak C–F···F–C intermolecular type II dihalogen interactions, yielding a 1D supramolecular polymeric chain. More than 80% of the total Hirshfeld surface area for favipiravir is occupied by H···H/C/N/O/F and C···N/O contacts. Energy frameworks have been calculated to additionally analyze the overall crystal packing. It was established that the structure of favipiravir is mainly characterized by the dispersion energy framework followed by the less significant electrostatic energy framework contribution. Finally, by using density functional theory (DFT) calculations and the quantum theory of atoms in molecules, we have assigned the interaction energy of each hydrogen bond, which can be helpful to develop scoring functions to be used in force fields/docking calculations. [ABSTRACT FROM AUTHOR] Copyright of Journal of the Iranian Chemical Society is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
ABSTRACT
Covid-19 Pneumonia of SARS-CoV-2 pandemic infection, persists to have high disease burden especially in cancer patients. Increased inflammation and thromboembolic processes are blamed to influence cancer patients more than the others but due to lack of knowledge regarding the pathophysiology of the both the virus itself and the response of the host, more basic and translational disease modeling research is needed to understand Cancer-Covid-19 interaction. In this study, serum samples from the patients, who were hospitalized due to Covid-19 pneumonia, applied to different cancer cells and cytotoxicity, motility, proliferation and gene expression analysis were performed. Serum samples derived from healthy volunteers and the fetal bovine serum that is used regularly in cell culture experiments used as controls. Hospitalized Covid-19 patients who had also cancer, were retrospectively screened, and their clinical course were recorded. Overall 12 Patient (PS) and 4 healthy serums (CS) were included in the experiments. PS applied cells showed increased motility in A549 cells as well as lost cell to cell connection in MCF7 and HCT116 cells, and induced expression of VIM, ZEB1 and SNAIL2 mRNA levels. Eight cancer diagnosed patients who were hospitalized due to Covid-19 between April and September 2020 were also reviewed retrospectively, which 5 of them were dead during SARS-CoV-2 infection. Thorax CT images of the 2 patients showed increased metastatic nodules in the lungs as of January 2021. The results of the study indicate that metastasis may be one of the prolonged consequences of COVID-19 pandemic in cancer sufferers.