ABSTRACT
The oral cavity, like the lungs, is often referred to as the <<ecological niche of commensal, symbiotic, and pathogenic or-ganisms,>> and the emigration and elimination of microbes between them are constant, ensuring a healthy distribution of saprophytic microorganisms that maintains organ, tissue, and immune homeostasis. The prolonged hospital stays due to COVID-19 complications, cross-infection, oxygenation therapy through the mask or incubation, and long-term intravenous infusions limit the patient's ability to care about the oral cavity, regularly clean teeth, floss interdental, etc., which creates extremely favorable conditions for colonization by aerobic and anaerobic pathogens of the oral cavity and periodontal pockets and leads to the rapid progression of chronic generalized periodontitis in this category of patients in the future. The goal of the study was to assess the state of the microbiome of the periodontal pockets of dental patients in the post-covid period. Methods. The object of the study was 140 patients with generalized periodontitis of the I and II stages of development in the chronic course (GP), among which 80 patients had coronavirus disease in the closest past. The patients were randomized by age, sex, and stage of GP development. The diagnosis of periodontal disease was established according to the classification by Danilevskyi. The bacteriological material for aerobic and facultative anaerobic microflora and yeast-like fungi was collected from periodontal pockets with a calibrated bacteriological loop and immediately seeded on blood agar. Results. Significant qualitative and quantitative changes in the nature of the oral microbiocenosis were observed in patients with GP after the recent coronavirus disease, compared with similar patients who did not suffer from COVID-19. We have noticed almost complete disappearance of bacteria that belong to the transient representatives of the oral microflora such as Neisseria, corynebacteria (diphtheria), micrococci, and lac-tobacilli. The main resident representatives of the oral microflora, i.e., alpha-hemolytic Streptococci of the mitis group, were found in all healthy individuals and patients of groups A and C, but in 30.0 +/- 4.58% of patients in group B, alpha-hemolytic streptococci in the contents of periodontal pockets are present in quantities not available for detection by the applied method (<2.7 lg CCU/mL). In terms of species, Streptococcus oralis and Streptococcus salivarius are more characteris-tic in gingival crevicular fluid in healthy individuals (93.8% of selected strains). In 68.4 +/- 3.32% of patients in group A, 64.0 +/- 3.43% of patients in group B, and 67.5 +/- 3.76% of patients in group C, the dominant species were Streptococcus gordonii and Streptococcus sanguinis (p<0.01), which increased pathogenic potential as they produce streptolysin-O, inhibit complement activation, bind to fibronectine, actively form biofilms on the surface of tooth enamel and gum epithelial surface, and can act as an initiator of adhesion of periodontal pathogens. The other representatives of the resident microflora of the oral cavity - Stomatococcus mucilaginosus and Veillonella parvula for the patients of group C are also found in periodontal pockets with a significantly lower index of persistence and minimal population level. In the post-covid period, both the population level and the frequency of colonization of periodontal pockets by Staphylo-cocci and beta-hemolytic Streptococci decreases rapidly. For these patient groups, unlike for those that did not suffer from COVID-19, we did not find any case of colonization with Staphylococcus aureus, as well as beta-hemolytic Streptococci and Epidermal staphylococcus were also absent. The most characteristic in the post-covid period is a decrease in the proportion of alpha-hemolytic Streptococci, an increase in the proportion of yeast-like fungi of Candida species, as well as the appearance of a significant number of gram-negative rod-shaped bacteria (Enterobacteria and Pseudomonads). In periodontal patien s, the microbial count is approximately 2 orders of magnitude lower than in those with GP who did not suffer from COVID-19 (p<0.05). Conclusions. The overpassed coronavirus disease due to intensive antibiotic therapy leads to a marked decrease in the number of viable saprophytic microorganisms in the periodontal pockets of patients with GP. In the post-covid period for the patients with GP, there is a decrease in the level of colonization of periodontal pockets by species of resident oral microflora - alpha-hemolytic Streptococci, reduction of resident micro-organism's species, and almost complete disappearance of transient microflora. On the other hand, the frequency of colonization of periodontal pockets by fungi species, enterobacteria, and pseudomonads significantly increases. There are more expressed disorders in the periodontal pocket's microbiome for the patients with a severe and complicated course of coronavirus disease, such as post-covid pulmonary fibrosis, which requires reconsideration of approaches to therapeutic and pharmacological treatment in this category of patients.Copyright © 2022, Zabolotny Institute of Microbiology and Virology, NAS of Ukraine. All rights reserved.
ABSTRACT
Synthesis of new Cefpodoxime derivatives via Schiff Bases mechanism and the efficiency of their antimicrobial and antiviral activities were addressed. They were analyzed for structural validation by using spectroscopic techniques using FTIR, 1HNMR, and 13CNMR. Molecular docking against IBV Virus papain-like protease (PLPro) was done with Auto dock tools against compounds having excellent IC50 values against IBV (Corona Class) virus. All derivatives showed strong zone of inhibition ranges from (55 ± 2.0 to 70 ± 0.8 mm) against E. coli. Compounds 1,2,4 and 6 derivatives showed remarkable activity against Stenotrophomonas maltophilia and Serratia marcescens. But For most the newly synthesized derivatives C 1 (64 ± 1.60), C 3 (32 ± 0.80), and C 8 (64 ± 1.60) showed potential IC50 values against two variants of Corona class viruses i.e. Avian Influenza (H9) and Avian corona (IBV) viruses. The current study revealed that newly synthesized Schiff Bases possessed strong anti-viral potential. Further studies may make a breakthrough in medical sciences to tackle latest challenges such as Corona Virus Diseases.
ABSTRACT
Background: COVID-19, first reported in China, from the new strain of severe acute respiratory syndrome coronaviruses (SARS-CoV-2), poses a great threat to the world by claiming uncountable lives. SARS-CoV-2 is a highly infectious virus that has been spreading rapidly throughout the world. In the absence of any specific medicine to cure COVID-19, there is an urgent need to develop novel thera-peutics, including drug repositioning along with diagnostics and vaccines to combat the COVID-19. Many antivirals, antimalarials, antiparasitic, antibacterials, immunosuppressive anti-inflammatory, and immunoregulatory agents are being clinically investigated for the treatment of COVID-19. Objectives: The earlier developed one parameter regression model correlating the dock scores with in vitro anti-SARS-CoV-2 main protease activity well predicted the six drugs viz remdesivir, chloroquine, favipiravir, ribavirin, penciclovir, and nitazoxanide as potential anti-COVID agents. To further validate our earlier model, the biological activity of nine more recently published SARS-CoV-2 main protease inhibitors has been predicted using our previously reported model. Methods: In the present study, this regression model has been used to screen the existing antiviral, an-tiparasitic, antitubercular, and anti pneumonia chemotherapeutics utilizing dock score analyses to explore the potential including mechanism of action of these compounds in combating SARS-CoV-2 main prote-ase. Results: The high correlation (R=0.91) explaining 82.3% variance between the experimental versus predicted activities for the nine compounds is observed. It proves the robustness of our developed model. Therefore, this robust model has been further improved, taking a total number of 15 compounds to formu-late another model with an R-value of 0.887 and the explained variance of 78.6%. These models have been used for high throughput screening (HTS) of the 21 diverse compounds belonging to antiviral, an-tiparasitic, antitubercular, and anti pneumonia chemotherapeutics as potential repurpose agents to combat SARS-CoV-2 main protease. The models screened that the drugs bedaquiline and lefamulin have higher binding affinities (dock scores of-8.989 and-9.153 Kcal/mol respectively) than the reference compound {N}-[2-(5-fluoranyl-1~{H}-indol-3-yl)ethyl]ethanamide (dock score of-7.998 Kcal/Mol), as well as higher predicted activities with pEC50 of 0.783 and 0.937 µM and the 0.611 and 0.724 µM respectively. The clinically used repurposed drugs dexamethasone and cefixime have been predicted with pEC50 val-ues of-0.463 and-0.622 µM and-0.311 and-0.428 µM respectively for optimal inhibition. The drugs such as doxycycline, cefpodoxime, ciprofloxacin, sparfloxacin, moxifloxacin, and TBAJ-876 showed moderate binding affinity corresponding to the moderate predicted activity (-1.540 to-1.109 µM). Conclusion: In the present study, validation of our previously developed dock score-based one parametric regression model has been carried out by predicting 9 more SARS-CoV-2 main protease inhibitors. Another model has been formulated to explore the model's robustness. These models have been taken as a barometer for the screening of more potent compounds. The HTS revealed that the drugs such as bedaqui-line and lefamulin are highly predicted active compounds, whereas dexamethasone and cefixime have optimal inhibition towards SARS-CoV-2 main protease. The drugs such as doxycycline, cefpodoxime, ciprofloxacin, sparfloxacin, moxifloxacin, and TBAJ-876 have moderately active compounds towards the target inhibition.