Anti-Infective Agents - Volume 21, Issue 1, 2023

Background: Since December 2019, COVID-19 has become a new health crisis in the world and has been declared a public health emergency of international concern by WHO. In search of anti-COVID treatment regimen, we applied molecular docking approach in order to identify the natural compounds that may have potential for anti-COVID treatment with specific target and selective inhibitory mechanism. Our goal is to identify the potential anti-COVID compounds based on virtual screening of the protein of spike glycoprotein as virtual inhibition target. Methods: Molecular docking was carried out by using Molergo Virtual Docker. 35 compounds from different plant sources were selected and docked in the enzyme pocket. Results: The docking result revealed that some of the compounds exhibited good potency against the virus and can be used further for developing new drug regimen. Conclusion: The compounds of natural origin could be a good target and can be used as lead compounds for the treatment of this dreadful disease.

Background: Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and patients with COVID-19 are managed mainly using repurposed conventional drugs, which target the viral entry and viral replication of SARS CoV-2 along with standard care and supportive therapy. Objective: This review article focuses on the potential benefits of black seeds (Nigella sativa) observed in clinical and in silico molecular docking studies of COVID-19. Methods: The literature was searched using databases such as LitCOVID, Web of Science, Google Scholar, bioRxiv, medRxiv, Science Direct, EBSCO, Scopus, EMBASE, and reference lists to identify published manuscripts or preprints related to the prevention or treatment of COVID-19 with black seeds (N. sativa) or their phytoconstituents. Results: Various clinical studies and in silico molecular docking studies determined that black seeds (N. sativa) and their bioactive phytoconstituents have potential activity against SARS CoV-2 infection. Conclusion: Patients with COVID-19 could be managed using black seeds (N. sativa) along with supportive care, which would speed up the recovery and decrease the mortality rate. More randomized controlled clinical trials would further establish the safety and efficacy of N. sativa in COVID-19 patients.

Coronavirus disease (COVID-19) is a pandemic disease caused by SARS-COV-2 that primarily attacks the respiratory system of the host. This disease was first reported in early December 2019, and the World Health Organization (WHO) classified the ongoing COVID-19 outbreak as a pandemic disease-causing global public health emergency by mid-January 2020. The human-to-human transmission occurs by droplets, infected hands, or surfaces with an incubation time of 2-14 days. It displays signs and symptoms, and if the disease progresses, it leads to death. To avoid symptomatic symptoms or increase infection severity, early diagnosis, quarantine, and supportive care can help to cure the patient infected with COVID-19. Several attempts have been projected for the development of vaccines against COVID-19. As of July 2, 2021, 600 vaccine candidates worldwide were evaluated against SARS-CoV-2, of which 300 have reached the preclinical stage of their development. Presently, Moderna (mRNA-1273), Shenzhen Geno-Immune Medical Institute (LV-SMENP-DC), Shenzhen Geno-Immune Medical Institute (Pathogen specific APC), CanSino Biologicals (Ad5-nCoV), Inovio Pharmaceuticals (INO-4800) have plunged into the phase I/II clinical trials (Source: ClinicalTrials.gov website; WHO). Scientists are increasingly seeking a key hide behind pathogenic pathways, epidemiological features, and future drug goals, which will lead to the development of successful strategies for prevention and treatment. Based on the current published data, we summarize the structure, life cycle of SARS-CoV-2 and the various product categories available as anti- COVID-19 agents (antiviral), with special emphasis on Chinese herbal medicines, which were licensed as anti-COVID agents by the Chinese Government. Such knowledge can be used as guidelines for COVID-19 clinical therapy.

Background: Mucormycosis is a genuine, however uncommon shrewd fungal contamination that spreads quickly, and subsequently brief analysis and treatment are important to stay away from the high pace of mortality and morbidity rates. Mucormycosis is brought about by the inward breath of its filamentous (hyphal structure) fungus, particularly in immunosuppressed patients. The pandemic of COVID -19 stays on an upsurge pattern. The second rush of this infection has prompted alarm in numerous nations, including India and a few pieces of the world experiencing the third wave. As there could be no appropriate treatment choices or cures accessible for this lethal contamination, steady consideration gears like oxygen chambers, ventilators and substantial utilization of steroids assume an imperative part in the management of COVID-19. Amidst this pandemic, the COVID-19 patients are procuring optional contaminations, for example, mucormycosis otherwise called black fungus infection. Objective: It is important to lead research on COVID-19 patients to even more likely to forestall and oversee pioneering contaminations to diminish their occurrence and bleakness. So, this paper is to foster preventive treatment plans and use corticosteroids sanely. Methods: Using search engines like Embase, PubMed, Google Scholar, etc., various research, review articles, and some book chapters, also various articles on websites and guidelines on the ICMR portal were accessed, after which we prepared this review article. In this review, we have included reported cases and case series of mucormycosis among patients with and without COVID-19 spanning the period of 1969 to 2021 and have described the clinical features and outcomes. Results: In gentle instances of COVID-19 (without hypoxemia) or when utilizing higher dosages of glucocorticoids, glucocorticoids ought to be kept away from ongoing investigations which have archived a disturbing number of COVID-19 patients with mucormycosis contamination. A large portion of these patients had diabetes which was controlled with the use of steroids. Conclusion: Thus, the current article underlines mucormycosis and its connected conditions, its component in typical and COVID-19 influenced people, affecting variables and difficulties to defeat this disease. Early distinguishing proof and further examination of its growth will altogether diminish the seriousness of the sickness and death rate in COVID-19- influenced patients.

Background: Pulicaria is a genus of the Asteraceae family, tribe Inuleae, containing 100 species with a distribution from Europe to North Africa to Asia. Objective: In this work, the study is focused on the difference in phytochemical and antibacterial activity of Pulicaria odora harvested in two regions of northern Algeria. Methods: Two maceration extraction methods were used; a stir plate at room temperature and bath shaker at 37 °C. Total phenolics and flavonoids were carried out using Folin-Ciocalteu and aluminium chloride methods, respectively. Antibacterial activity was evaluated by agar diffusion method on four bacterial strains Listeria innocua, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Results: The results found showed that the highest total polyphenol content was 271,8 ± 22, 52 mg gallic acid equivalent/g dry matter (mg GAE/g of DM); the best flavonoid content is 51,53 ± 4,42 mg quercetin equivalent / g of dry matter (mg QE/g of DM) harvested in Bejaia. The best levels of total polyphenols and flavonoids from the plant harvested in the region of Tizi-Ouzou are 218,23 ± 12.33 mg GAE / g of DM, 54,15 ± 5,98 mg QE/ g DM respectively. The two phenolic extracts obtained by the two solvents at a concentration of 70% are more active against S. aureus (17.66 mm for the sample of Bejaia at the concentration of 1mg /20μL), while a moderate sensitivity is recorded against other strains for the two samples. Conclusion: Pulicaria odora leaf extract is strong against bacterial infection and can be used as medicinal remedy and in food industry.

Background: Tuberculosis is a highly contagious disease that is one of the major causes of mortality worldwide and the leading infectious organism-related cause of death. Various tetrazole and quinazoline compounds have been successfully developed in the past for tuberculosis treatment. In this case, we planned to design the hybrid moieties by combining both tetrazole and quinazoline nuclei to create novel compounds with increased activity. Methods: 6, 6-dimethyl-5, 6, 7, 9–tetrahydrotetrazolo [5, 1-b] Quinazolin-8(4H) -one derivatives were synthesized, characterized by using spectral data. The antitubercular activity of the synthesized compounds was tested against the H37RV strain of Mycobacterium tuberculosis. In order to identify the interactions with the target protein Mtb Pks13 Thioesterase domain in complex with an inhibitor, docking analysis of the final compounds was performed (Protein data bank ID: 5V41). To verify their drug-like potential, the synthesized compounds were subjected to Pharmacokinetic prediction experiments. Zebrafish larvae had been used to test the teratogenicity of the synthesized compounds. Results: At 6.25 μg/mL, compounds F4 and F7 exhibited good efficacy against Mycobacterium tuberculosis strains. Docking studies aided in determining the most likely binding mode within the binding cavity of the concerned target protein. Conclusion: Compounds containing p-fluorophenyl and p-nitrophenyl groups as substituents were found to have excellent anti-tubercular activity.

Background: According to the reports from the World Health Organization, increased use of antibiotics and bacterial resistance has become a worldwide issue. Resistance to antimicrobial agents in Escherichia coli clinical strains is increasing. Objective: The objective of this study was to determine the antibiotic resistance patterns and frequency of multidrug resistance (MDR) phenotype in E. coli isolated from patients in two major hospitals in Sari, north Iran. Methods: In this descriptive-analytical study, a total of 13322 clinical specimens were collected from patients. All the specimens were evaluated to determine the presence of E. coli strains using conventional biochemical tests and API kit. Susceptibility testing against twelve antibiotics was determined using the disk-diffusion method. Results were interpreted in accordance with the Clinical and Laboratory Standard Institute (CLSI) protocol. Results: Out of 13322 studied samples, 964 (7.23%) E. coli strains were identified. In two hospitals, high resistance to ampicillin and cefalexin was presented in 621 (64.4%) and 402 (41.7%) isolates, respectively. The highest antibiotic resistance was observed in the burn unit, the burn intensive care unit (ICU) and the burn restoration section, while all the strains (eight) that were isolated from the neonatal-ICU, were sensitive to all the tested antibiotics except cefalexin, nitrofurantoin, nalidixic acid, and ampicillin. Also, strains isolated from urine, wound, stool, and blood samples were resistant to all tested antibiotics. Conclusion: Increased resistance to different antibiotics in burn hospitals has created increasing concern. Very high resistance to some antibiotics indicates that these drugs are misused in therapeutic centers and highlights that infection control measures should be arranged in the ICUs of our hospitals.

Background: Seeking new specific and effective drugs against Coronavirus Diseases-2019 (COVID-19) is of great importance. This study describes the efficacy of remdesivir with supportive care alone in the treatment of critically sick adult and child COVID-19 patients. Methods: This study was a one-blind placebo-controlled, randomized clinical trial in adults (aged≥18 years) and children (aged≤12 years) in Iran. Patients were included if they had positive PCR test for SARS-CoV-2 infection, O2 saturation ≤88%, and compatible symptoms. All participants received standard care following national treatment guidelines. The treatment group received remdesivir (200 mg IV on day 1 and followed by 100 mg in single daily infusions). The control group received standard care and an identical volume of placebo infusions (Water for injection) for 5 days. For pediatric patients, the intervention group received remdesivir (5mg/kg on the first day and then 5.2 mg/kg on days 2 to 5). Discharge from the hospital within 10 days of first treatment is considered as the primary endpoint of the study. Admission in the intensive care unit (ICU) is considered as original secondary endpoint of the study. Results: 141 patients were enrolled and randomly assigned to two group (adults; 54 patients in the intervention group vs. 52 patients in the control group, and children; 17 patients in the intervention group vs. 18 patients in the control group). The mean time from the first symptoms until the referral to the hospital in adult patients was 5.61 ± 2.67 day and 4.80±1.48 day for intervention and control groups, respectively. The mean time from the first symptoms until death was reported to be significant and was longer for intervention group than the control group (24.83 ± 11.25 vs. 10.50 ± 2.42 day; p value=0. 012). For children who received remdesivir, the mean time between admission until death was reported to be significant, as the finding highlighted a longer time duration for the intervention group (13.55 ± 0.72 vs. 10.66 ± 0.57 day; p value=0. Mechanicalanical ventilation was used in 17 patients (100%) and 18 patients (100%) in the intervention and control groups, respectively (p value=0.853). Conclusion: Among patients with critical COVID-19, those randomized to a 5-day treatment of remdesivir did have a statistically significant difference in clinical status compared with the control group of both adults and children.