Novel Galactopyranoside Esters: Synthesis, Mechanism, In Vitro Antimicrobial Evaluation and Molecular Docking Studies.

One-step direct unimolar valeroylation of methyl α-D-galactopyranoside (MDG) mainly furnished the corresponding 6-O-valeroate. However, DMAP catalyzed a similar reaction that produced 2,6-di-O-valeroate and 6-O-valeroate, with the reactivity sequence as 6-OH > 2-OH > 3-OH,4-OH. To obtain novel antimicrobial agents, 6-O- and 2,6-di-O-valeroate were converted into several 2,3,4-tri-O- and 3,4-di-O-acyl esters, respectively, with other acylating agents in good yields. The PASS activity spectra along with in vitro antimicrobial evaluation clearly indicated that these MDG esters had better antifungal activities than antibacterial agents. To rationalize higher antifungal potentiality, molecular docking was conducted with sterol 14α-demethylase (PDB ID: 4UYL, Aspergillus fumigatus), which clearly supported the in vitro antifungal results. In particular, MDG ester 7-12 showed higher binding energy than the antifungal drug, fluconazole. Additionally, these compounds were found to have more promising binding energy with the SARS-CoV-2 main protease (6LU7) than tetracycline, fluconazole, and native inhibitor N3. Detailed investigation of Ki values, absorption, distribution, metabolism, excretion, and toxicity (ADMET), and the drug-likeness profile indicated that most of these compounds satisfy the drug-likeness evaluation, bioavailability, and safety tests, and hence, these synthetic novel MDG esters could be new antifungal and antiviral drugs.

Side Effects of Mixing Vaccines against COVID-19 Infection among Saudi Population.

BACKGROUND: Mixing two different vaccines has been utilized to minimize the impact of any supply chain interruptions and to combat the COVID-19 pandemic in Saudi Arabia. We conducted this study to evaluate the side effects, if any, associated with the mixed vaccination approach. METHODS: An online survey study was administered among COVID-19 vaccine recipients in Saudi Arabia. Symptoms post vaccination were assessed in 311 vaccinated participants with two matched doses of either Oxford-AstraZeneca or Pfizer-BioNTech vaccines, or two mixed doses, respectively. RESULTS: After the second dose, around 31% of the matched vaccine group reported no symptoms, while only 6% of the mixed vaccine group reported no symptoms. Most of the side effects after the second dose associated with matched vaccines were injection site pain (46%), while the mixed vaccines group reported significantly more symptoms compared with the matched vaccine group, which included fever (41%), fatigue (66%), muscle pain (44%), chills (17%) and injection site pain (60%). CONCLUSION: The data suggest the overall safety of the mixed vaccination protocol; however, it might be associated with side effects such as fever, fatigue, muscle pain, chills, and injection site pain. Further studies with a larger cohort size could shed more light on this aspect, which would be imperative for deciding to utilize a mixed vaccination approach.

Bacterial Coinfections Increase Mortality of Severely Ill COVID-19 Patients in Saudi Arabia.

Coronavirus disease 19 (COVID-19) is an ongoing global pandemic that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The severity and mortality rates of COVID-19 are affected by several factors, such as respiratory diseases, diabetes, and hypertension. Bacterial coinfections are another factor that could contribute to the severity of COVID-19. Limited studies have investigated morbidity and mortality due to microbial coinfections in COVID-19 patients. Here, we retrospectively studied the effects of bacterial coinfections on intensive care unit (ICU)-admitted patients with COVID-19 in Asir province, Saudi Arabia. We analyzed electronic medical records of hospitalized patients with COVID-19 at Asir Central Hospital. A total of 34 patients were included, and the clinical data of 16 patients infected with SARS-CoV-2 only and 18 patients coinfected with SARS-CoV-2 and bacterial infections were analyzed in our study. Our data showed that the length of stay at the hospital for patients infected with both SARS-CoV-2 and bacterial infection was 35.2 days, compared to 16.2 days for patients infected with only SARS-CoV-2 (p = 0.0001). In addition, higher mortality rates were associated with patients in the coinfection group compared to the SARS-CoV-2-only infected group (50% vs. 18.7%, respectively). The study also showed that gram-negative bacteria are the most commonly isolated bacteria in COVID-19 patients. To conclude, this study found that individuals with COVID-19 who presented with bacterial infections are at higher risk for a longer stay at the hospital and potentially death. Further studies with a larger population are warranted to better understand the clinical outcomes of COVID-19 with bacterial infections.