Current Drug Therapy - Volume 18, Issue 3, 2023

Background: As the COVID era unfolds, researchers reveal that rapid changes in viral genetic material allow viruses to circumvent challenges triggered by the host immune system and resist anti-viral drugs, potentially leading to persistent viral manifestations in host cells. Molnupiravir (RNA-dependent RNA polymerase inhibitor) is a novel anti-viral medicine promising a vital role in coming setbacks. Objectives: This review aims to clarify the safety and efficacy of the molnupiravir molecule in light of existing case studies. As a result, it is intended to explore and discuss the molecular structure, mechanism of action, discovery and development process, preclinical research, clinical investigations, and other subtopics. Methods: A total of 75 publications were searched using multiple engines, such as Google Scholar, PubMed, Web of Science, Embase, Cochrane Library, ClinicalTrials.gov, and others, with a constraint applied to exclude publications published over 11 years ago. Molnupiravir, safety, efficacy, COVID- 19, RdRp, PK-PD, and clinical study were utilized as keywords. Results: Clinical results on molnupiravir are supported by investigations that were recently disclosed in a study on both sex volunteers (male and female) with an age restriction of 19 to 60 years, followed by a Phase-3 Clinical Trial (NCT04575584) with 775 randomly assigned participants and no fatalities reported due to treatment. Conclusion: Molnupiravir proved a high level of safety, allowing it to be tested further. This review supports the safety and efficacy of this molecule based on the established evidence, which claims the most anticipated employment of molnupiravir in COVID protocol.

Background: Nanotechnology is moving toward future goals in the field of medicines, cosmetics and hospitality due to the size reduction of material in the range of 1-100nm, enhancing the stability and bioavailability of the material. Objective: This review includes the progress in the field of nanotechnology, its advantages, understanding and applications in antimicrobial therapy. Methods: The manuscripts were collected in the field of antimicrobial research with the help of nanotechnology platforms from different sources like PubMed, ScienceDirect and Google. A total of 236 manuscripts were collected and analyzed, out of which 93 were relevant and considered for the present manuscript. Results: There are diverse forms of metallic nanomaterials that show antimicrobial properties, such as gold, silver, copper, zinc, titanium and many such metal oxides. Various carriers are used to deliver the drug at targeted sites via encapsulating the nanomaterial in polymers, liposomes or in the lipoidal structure. The inhibition of microorganism growth may be attributed to different mechanisms like destroying the synthesis of a cell wall, nucleic acid, injury to the bacteria cell wall and inhibiting the metabolic pathways in bacteria. This enhanced the antimicrobial activity and reduced the toxicity that could be significant due to a reduction in the dose proportionality. Conclusion: The recent advances in drug delivery with the help of liposomes, solid lipid nanoparticles, dendrimers, and various nanoparticles led to effective prevention, treatment and diagnosis of various microbial infections and this could dramatically change the way antimicrobial therapy explored for reducing drug resistance.

Introduction: Yellow fever is an infectious disease endemic to Africa, and Central and South America with a significant impact on public health, causing outbreaks and epidemics. Clinical manifestations can vary from asymptomatic to more severe and lethal disease outcomes. The primary prevention of yellow fever occurs through the vaccination of individuals, which confers immunity for life. Patients with chronic kidney disease, especially those undergoing dialysis, have low vaccination and seroconversion rates. As mentioned above, this research aimed to perform a systematic review of the yellow fever vaccination protocol in hemodialysis patients. Methods: A systematic review on vaccination against yellow fever in hemodialysis patients using databases, PubMed and Biblioteca Virtual em Saúde (BVS), was performed. For data collection, combinations were made using the following descriptors: protocols, vaccination, yellow fever, kidney dialysis, chronic kidney failure, chronic kidney disease, and group risk included in the title and abstract description. Articles with no subject related to the search were excluded and also if they were duplicated. Results: In this review, 90 scientific articles were identified in both databases. After applying exclusion criteria, a total of 3 articles were selected. Conclusion: We recommend carefully assessing the risk-benefit and contraindications for the patient, emphasizing the risk groups. There is an evident lack of studies on the subject, and there is a need to broaden investigations related toimmunization for patients on dialysis. The review is registered in the PROSPERO system with the number 323550.

Background: Since patients admitted to the intensive care unit have a compromised immune system and are more prone to infection than other patients, timely diagnosis and treatment of corneal ulcers among this group of patients can prevent vision loss. Therefore, it is necessary to treat eye infections and corneal ulcers promptly and economize prohibitive costs. Objective: Appropriate treatment with the most effective antibiotic before the answer is available to prevent corneal ulcer complications and blindness. Methods: This study was conducted from November 2019 to November 2020 and after approval by the ethics committee of Hamedan University of Medical Sciences with the code of ethics: IR.UMSHA.REC.1398.716. First, the corneal secretions of 121 patients admitted to the intensive care unit of Sina Hospital are prepared by an ophthalmologist (after anesthetizing the cornea with tetracaine drops and sterile swabs) and culture in four growth mediums (blood agar, chocolate agar, thioglycolate, and EMB). Microbial cultures are examined after 48 hours and a fungal culture is examined one week later. Disc diffusions are placed in positive microbial cultures. Antibiotic susceptibility or resistance of the antibiogram was recorded. Other demographic data, including patients' age and sex, are extracted from ICU files. Also, test results and patient identifications are recorded in a checklist designed for this purpose. Results: Of all the antibiotics used against common bacteria, vancomycin (84%), colistin (80.43%), cefazolin (80%), and levofloxacin (60%) had the highest sensitivity and gentamicin (93.75%), ceftazidime (86.42%) Erythromycin (85%) had the highest resistance against isolated bacteria. Conclusion: The data obtained from this study showed that the most common microorganisms in the age group under the age of 30 years were Acinetobacter Baumannii, in the group of 30-60 years old was Klebsiella pneumonia, and age group over 61 years old was Staphylococcus aureus, and the most sensitive antibiotics in the age group under 30 years were vancomycin and levofloxacin and the age group30-60 were colistin and vancomycin and in the age group over 61 years were vancomycin and cefazolin.

Background: The present work describes the systematic development and optimization of cyclosporine-A loaded biodegradable polymeric nanoparticulate system using quality by design paradigm, to achieve an effective and sustained release of the cyclosporine-A to the targeted lesion of plaque psoriasis. Methods: The polymeric nanoparticles were formulated using the solvent emulsification method using Polycaprolactone and Hyaluronic acid as polymers. An Ishikawa fishbone diagram was constructed for risk assessment and to describe various plausible product and process variables influencing the quality target product profile. Critical process and product parameters were further optimized by Response surface methodology using Central Composite Design by Minitab 19 Software. The development and optimization of cyclosporine-A loaded biodegradable polymeric nanoparticles were further carried out by developing the relationship of independent variables viz. amount of polymers polycaprolactone and hyaluronic acid on dependent variables viz. particle size, zeta potential, and entrapment efficiency and exploring their interactions. Validation of the model was done by checkpoint analysis method. Results: The particle size, zeta potential, and Entrapment efficiency of the optimized polymeric nanoparticles were found to be 317.2 ± 1.271, -0.249 ± 0.903 mV and 83.33 ± 1.124%, respectively. SEM images of the lyophilized nanoparticles showed spherical particles. In-vitro drug release study showed a slow and sustained release of 88.52 ± 1.10% of drugs up to 14 days. Conclusion: The nanoparticulate system would also help in overcoming the problem associated with poor water solubility and low permeability of the drug and will explore drug loaded biodegradable polymeric nanoparticles as a novel platform for effective therapy of psoriasis.

Background: Methotrexate is a cytotoxic chemotherapeutic agent that has severe side effects, such as nephrotoxicity. Momordica charantia is a bright yellow-orange fruity plant that has been shown to have antioxidant, antidiabetic, and anti-inflammatory properties. Objective: This study scrutinized the protective effects of Momordica charantia extract against methotrexate- induced nephrotoxicity. Methods: 24 Sprague Dawley male rats were divided into three experimental groups (8 rats in each): Control (C); Methotrexate (MTX); and Methotrexate plus Momordica charantia (MTX+MC). All rats were fed ad libitum and tap water. Methotrexate was administered at 20 mg/kg intraperitoneally as a single dose. In the MTX+MC group, MC was administered at a dose of 50mg/kg for 5 days orally. At the end of the 5th day, the rats were decapitated and kidney samples were taken to analyze glutathione (GSH), malondialdehyde (MDA), myeloperoxidase (MPO), 8-hydroxy-2'-deoxyguanosine (8-OHdG) and caspase-3 activity. Data was analyzed with GraphPad Prism 5.0. Results: Findings showed that while there was a significant increase in MDA, MPO, 8-OHdG levels, and an essential reduction in GSH levels in the MTX-treated group when compared with the control group, bitter melon treatment significantly reversed MDA, MPO, and 8-OHdG levels (p< 0.001). GSH level elevation was observed in the MTX-MC group when compared to the MTX-treated group (p< 0.001). Conclusion: This study showed that bitter melon is thought to have a protective effect against kidney damage caused by methotrexate. With future studies, we believe that the use of bitter melon extract as a protective agent in kidney damage caused by drug-induced oxidative damage will bring an innovative approach to treatment.

Background: This study aims to develop a new hepatoprotective drug from common plants and vitamins that are potent, nontoxic, and cost-effective. The literature search found that Curcuma longa , Zingiber officinale, Terminalia, chebula, and Vitamin A (Vitamin C + Vitamin E) provide hepatoprotective action against drugs-induced hepatotoxicity. A major side effect of antitubercular drugs (ATD) is liver toxicity, which reduces their effectiveness. Aim: In this study, Vitamins and Phytoconstituents (Combined extract) were evaluated for their potential hepatoprotective effects against hepatotoxicity induced by antitubercular drugs in Wistar albino rats of either sex. Materials and Methods: In the study, ethanolic extract of rhizomes of Curcuma longa and Zingiber officinale , fruits of Terminalia chebula , and vitamins C and E were used. As a standard drug, silymarin was also used. For 30 days, albino rats received 7.5 mg/kg isoniazid, 10 mg/kg rifampicin, and 35 mg/kg pyrazinamide orally as a suspension in distilled water. Result: A combined extract plus vitamins (500mg/kg) treatment significantly reduced the hepatic toxicity caused by antitubercular drugs (P<0.05-P<0.001). A combination of extracts + vitamins (500mg/kg) eliminates hepatotoxicity, and the results are close to those of Silymarin, a standard drug. Conclusion: As a result of this study, extracts+vitamins provide protection against liver injury attributed to their hepatoprotective activity, which supports their traditional use.

Background: Cancer is a leading cause of death for people worldwide, in addition to the rise in mortality rates attributed to the Covid epidemic. This allows scientists to do additional research. Here, we have selected Integerrimide A, cordy heptapeptide, and Oligotetrapeptide as the three cyclic proteins that will be further studied and investigated in this context. Methods: Docking research was carried out using the protein complexes 1FKB and 1YET, downloaded from the PDB database and used in the docking investigations. Cyclopeptides have been reported to bind molecularly to human HSP90 (Heat shock protein) and FK506. It was possible to locate HSP90 in Protein Data Banks 1YET and 1FKB. HSP90 was retrieved from Protein Data Bank 1YET and 1FKB. Based on these findings, it is possible that the anticancer effects of Int A, Cordy, and Oligo substances could be due to their ability to inhibit the mTOR rapamycin binding domain and the HSP90 Geldanamycin binding domain via the mTOR and mTOR chaperone pathways. During the calculation, there were three stages: system development, energy reduction, and molecular dynamics (also known as molecular dynamics). Each of the three compounds demonstrated a binding affinity for mTOR's Rapamycin binding site that ranged from -6.80 to -9.20 Kcal/mol (FKB12). Results: An inhibition constant Ki of 181.05 nM characterized Cordy A with the highest binding affinity (-9.20 Kcal/mol). Among the three tested compounds, Cordy A was selected for MD simulation. HCT116 and B16F10 cell lines were used to test each compound's anticancer efficacy. Doxorubicin was used as a standard drug. The cytotoxic activity of substances Int A, Cordy A, and Oligo on HCT116 cell lines was found to be 77.65 μM, 145.36 μM, and 175.54 μM when compared to Doxorubicin 48.63 μM, similarly utilizing B16F10 cell lines was found to be 68.63 μM, 127.63 μM, and 139.11 μM to Doxorubicin 45.25 μM. Conclusion: Compound Cordy A was more effective than any other cyclic peptides tested in this investigation.

Background: Untreated cardiovascular disease (CVD) can commonly cause disability and morbidity and increase the mortality risk. Objective: This systematic review and meta-analysis study aimed to investigate the pain-relieving effects of aromatherapy with medicinal plants on patients with cardiovascular diseases. Methods: This meta-analysis followed PRISMA guidelines. Several keywords were explored using an extensive search of databases, including PubMed, Web of Science (ISI), EMBASE, and Scopus, on May 15, 2022. In addition, an excel form was designed for recording the data of the RCT studies. Standardized mean difference (SMD) and their 95% confidence intervals (CI) were used to estimate the overall effect size. The Cochran Q test and the statistic I2 were used to evaluate the heterogeneity of studies. Lastly, Egger's and Begg's tests were used to assess potential publication bias. Results: We included studies examining the effect of inhalation aromatherapy on pain in patients with CVD after 5 minutes (five papers) and 15-30 minutes (six papers) of intervention. The results showed a significant decrease in pain in the intervention group compared to the control group after 5 minutes (SMD = -2.25, 95% CI = -3.21 to -1.29, P < 0.001) and after 15-30 minutes (SMD = -3.22, 95% CI = - 4.41 to -2.03, P < 0.001) of intervention in CVD patients. No publication bias was observed related to the association between inhalation aromatherapy and pain relief. Conclusion: In CVD patients, inhalation aromatherapy could significantly reduce pain severity and can be used as a complementary medicine for pain reduction.