The Effects of Medications and the Roles of Pharmacists on the Recovery of Patients with COVID-19 Infection: An Epidemiological Study from the United Arab Emirates.

Patients infected with coronavirus have new experiences and hence new needs from the healthcare sector. Acknowledging patients' experiences can exhibit promising outcomes in coronavirus management. Pharmacists are considered a vital pillar in managing patients' experiences during their infection. A cross-sectional study was conducted to assess the experiences of COVID-19-infected individuals and the roles of pharmacists in the United Arab Emirates. The survey was face- and content-validated after being developed. Three sections were included in the survey (demographics, experiences of infected individuals, and the roles of pharmacists). Data were analyzed using the Statistical Package for the Social Sciences. The study participants (n = 509) had a mean age of 34.50 (SD = 11.93). The most reported symptoms among participants were fatigue (81.5%), fever (76.8%), headache (76.6%), dry cough (74.1%), muscle or joint pain (70.7%), and sore throat (68.6%). Vitamin C was the most used supplement (88.6%), followed by pain relievers (78.2%). Female gender was the only factor associated with symptom severity. About 79.0% agreed that the pharmacist played an important and effective role during their infection. The most reported symptom was fatigue, with females reporting more severe symptoms. The role of the pharmacist proved to be vital during this pandemic.

The Discovery of Small Allosteric and Active Site Inhibitors of the SARS-CoV-2 Main Protease via Structure-Based Virtual Screening and Biological Evaluation.

The main protease enzyme (Mpro) of SARS-CoV-2 is one of the most promising targets for COVID-19 treatment. Accordingly, in this work, a structure-based virtual screening of 3.8 million ligand libraries was carried out. After rigorous filtering, docking, and post screening assessments, 78 compounds were selected for biological evaluation, 3 of which showed promising inhibition of the Mpro enzyme. The obtained hits (CB03, GR04, and GR20) had reasonable potencies with Ki values in the medium to high micromolar range. Interestingly, while our most potent hit, GR20, was suggested to act via a reversible covalent mechanism, GR04 was confirmed as a noncompetitive inhibitor that seems to be one of a kind when compared to the other allosteric inhibitors discovered so far. Moreover, all three compounds have small sizes (~300 Da) with interesting fittings in their relevant binding sites, and they possess lead-like characteristics that can introduce them as very attractive candidates for the future development of COVID-19 treatments.

Allosteric Binding Sites of the SARS-CoV-2 Main Protease: Potential Targets for Broad-Spectrum Anti-Coronavirus Agents.

The current pandemic caused by the COVID-19 disease has reached everywhere in the world and has affected every aspect of our lives. As of the current data, the World Health Organization (WHO) has reported more than 300 million confirmed COVID-19 cases worldwide and more than 5 million deaths. Mpro is an enzyme that plays a key role in the life cycle of the SARS-CoV-2 virus, and it is vital for the disease progression. The Mpro enzyme seems to have several allosteric sites that can hinder the enzyme catalytic activity. Furthermore, some of these allosteric sites are located at or nearby the dimerization interface which is essential for the overall Mpro activity. In this review paper, we investigate the potential of the Mpro allosteric site to act as a drug target, especially since they interestingly appear to be resistant to mutation. The work is illustrated through three subsequent sections: First, the two main categories of Mpro allosteric sites have been explained and discussed. Second, a total of six pockets have been studied and evaluated for their druggability and cavity characteristics. Third, the experimental and computational attempts for the discovery of new allosteric inhibitors have been illustrated and discussed. To sum up, this review paper gives a detailed insight into the feasibility of developing new Mpro inhibitors to act as a potential treatment for the COVID-19 disease.

Computer-aided approaches reveal trihydroxychroman and pyrazolone derivatives as potential inhibitors of SARS-CoV-2 virus main protease.

COVID-19 was declared a pandemic by the World Health Organization (WHO) in March 2020. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2). The aim of this study is to target the SARS-CoV-2 virus main protease (Mpro) via structure-based virtual screening. Consequently, > 580,000 ligands were processed via several filtration and docking steps, then the top 21 compounds were analysed extensively via MM-GBSA scoring and molecular dynamic simulations. Interestingly, the top compounds showed favorable binding energies and binding patterns to the protease enzyme, forming interactions with several key residues. Trihydroxychroman and pyrazolone derivatives, SN02 and SN18 ligands, exhibited very promising binding modes along with the best MM-GBSA scoring of -40.9 and -41.2 kcal mol-1, resp. MD simulations of 300 ns for the ligand-protein complexes of SN02 and SN18 affirmed the previously attained results of the potential inhibition activity of these two ligands. These potential inhibitors can be the starting point for further studies to pave way for the discovery of new antiviral drugs for SARS-CoV-2.