Recent advances in anti-infective drug discovery最新文献

Background: Convalescent plasma has been used to provide passive immunotherapy to patients with COVID-19 with a high level of safety. Very few efficacy studies were available, and due to COVID being a relatively new disease, its exact therapeutic role was unclear. This observational study on the impact of COVID convalescent plasma (CCP) on clinical outcomes attempts to evaluate the effectiveness of convalescent COVID-19 plasma therapy in the treatment of COVID-19 patients at the tertiary care center in the Uttarakhand state of India.

Methods: CCP was collected by plasmapheresis/whole blood from willing COVIDrecovered donors who underwent pre-donation testing including ABO and RhD grouping, mandatory blood screening tests for HIV, HBV, HCV, syphilis and Malaria, Haemoglobin estimation and COVID IgG assay. Hospitalized patients with severe COVID-19 pneumonia who received these CCP units were followed up and the outcome (Recovery/death) was observed.

Results: A total of 63 patients who received CCP were included in the study. Out of the total, 13 (20.7%) were females and 50 (79.3%) were males and their ages ranged from 24 to 80 years with a median age of 53 years. The period between the start of symptoms and hospitalization ranged from 1 to 14 days with an average duration of 4.7 days. Symptoms on presentation included Fever 53/63 (84.1%), Tachypnoea 60/63 (95.2%) and Cough 42/63 (66.7%). Among these patients, 22/63 (34.9%) were on non-invasive ventilation (NIV), 6/63 (9.5%) on non-rebreather mask (NRBM) and 32/63 (50.8%) were on Ventilator support. The infused convalescent plasma had a Mean IgG value of 57.3 AU with a range of (10-142 AU). A total of 37 (58.7%) patients were lost to COVID-19 infection and 26 (41.3%) were discharged from the hospital in a healthy state.

Conclusion: The use of convalescent plasma in addition to standard treatment in our study on patients with severe pneumonia due to COVID-19 did not demonstrate reduced mortality of COVID-19 patients amidst numerous variables. The results showed that the use of convalescent plasma as a treatment option in the present conditions needs a serious re-evaluation. Studies on a strictly defined recipient group and transfusion of CCP units, with adequate antibody titer and/or neutralization activity, must be analyzed for future works.

Pulegone ((R)-5-Methyl-2-(1-methylethylidine) cyclohexanone) is a pharmacologically active, natural monoterpene ketone obtained from leaves and flowering tops of the mint family (Lamiaceae). The aim is to comprise the physicochemical and biological aspects of pulegone. All significant databases were collected via electronic search using Pubmed, Scopus, Web of Science, and Science Direct and were compiled. This review presents the occurrence, chemistry, and modifications of pulegone structure and its effect on the biological system. Pulegone represents various pharmacological properties, i.e., antioxidant, antimicrobial, anti-feeding, antifungal, antiviral, and pesticide activities, and has a significant role as an abortifacient and emmenagogue. Thus, this present review concludes the knowledgeable erudition on pulegone that paves the way for further work.

Background: The human respiratory syncytial virus (RSV) is responsible for causing upper and lower respiratory tract infections in young children. RSV Fusion (F) protein is a surface glycoprotein that facilitates virus entry into host cells. Thus, newer designing of RSV Fusion (F) protein inhibitors is required on an urgent basis.

Methods: In the present study, we have developed statistically robust. Quantitative structure-activity relationship (QSAR) models for the effective designing of newer analogues of piperazinylquinoline derivatives (H1-H12).

Results: Our developed models were retained with high statistical parameters (R² > 0.6 and Q² > 0.5). Our developed pharmacophore, model (AADHRR_2) (indicating that two hydrogen bond acceptors, one hydrogen bond donor, one hydrophobic group, and two aromatic rings) is crucial for retaining the activities of piperazinylquinoline derivatives against RSV. Moreover, docking analysis of 12 new analogues on RSV pre-F in complex with 5C4 Fab (PDB ID: 5W23) and post-F trimeric protein (PDB ID: 3RRR) suggested higher affinities of these molecules against studied targets with good docking scores.

Conclusion: Thus, one can implement developed QSAR models, docking analogy and Pharmacophore models for identifications of potent leads for designed molecules as RSV Fusion (F) protein inhibitors.

Introduction: COVID-19 causes significant pulmonary microthrombi in some individuals, leading to ARDS and death. Thrombolysis could be an effective approach in some patients with severe ARDS. We describe our experience with the usage of thrombolytic agents in critically ill COVID-19 patients who were in worsening respiratory failure.

Methods: Retrospective chart analysis was done in patients who were thrombolysed between May 2020-Sept 2020. Analysis was done to find out factors associated with improvement in oxygenation and survival.

Results: Twenty-seven patients with severe ARDS [all had respiratory rate >30, FiO2 >0.6 (on NIV/HFNC) and PiO2/FiO2 ratio <120] were thrombolysed in our ICU for COVID19 causes. C.T. Pulmonary Angiography could not be done in any of the 27 patients due to poor general condition, but 2D echo was normal in most (5 had dilated RA, RV), and none of the patients was in shock. So, there was no conventional indication of thrombolysis in these patients, yet after thrombolysis, we observed dramatic changes in oxygenation (defined by a decrease in FiO2 by ≥0.2) in twenty patients. Five patients had a major bleed. Eleven patients survived (survival rate of 40.7%) and the survival rate was high {66% (8/12)} in patients who were thrombolysed within 2 days of oxygen requirement.

Conclusion: In this unprecedented pandemic with high mortality rates, efficacy of early thrombolysis needs to be further explored in randomised controlled trials.

Background: High-performance thin-layer chromatography (HPTLC) was developed and validated for the determination of aloe-emodin in accordance with ICH guidelines. In addition, a novel RP-UHPLC method was developed, and both methods were used to analyse the herbal extract and herbal formulation.

Methods: Separation was carried out on a silica gel 60 F₂₅₄ HPTLC plate using the mobile phase Toluene: Methanol (9:1). The linearity was good across the 800-4000 ng/spot range. Validation results are within acceptable limits. The percent RSD for accuracy was 0.58-1.77, and precision was 1.10-1.97 and 1.45-1.94 for intraday and interday, respectively. The percentage of aloe-emodin found in the herbal extract and aloe vera capsule was 99.83 ± 1.19 and 99.53 ± 1.29, respectively, using this method.

Results: Quantification of aloe-emodin in herbal extract and herbal formulation were done using a novel UHPLC method with chromatographic conditions of orthophosphoric acid Methanol (0.1 percent OPA): Water (65:35, v/v) and pH 3, a flow rate of 1.2 ml/min, and elute detection at 254 nm. At 6.32 minutes, a sharp and symmetric peak was observed. The method developed was validated in accordance with ICH guidelines. The percent RSD numerical value of accuracy was 0.304-0.576, and the inter-day and intraday precision were 0.32-3.08 and 0.51-2.78, respectively. Herbal extract and aloe vera capsule were analysed using the new UHPLC method. Aloe-emodin percentages were reported as 100.3 ± 0.89 and 99.53 ± 1.29, respectively.

Conclusion: The antimicrobial and anti-oxidant activities of an aloe-vera herbal formulation were studied, and the results were positive.

Background: Considering the role of calcium in the replication and morphogenesis of rotaviruses, it is hypothesized that decreased cytosolic calcium levels by using calcium channel blockers can subsequently interfere with rotavirus replication.

Objective: The present study investigated the effects of two calcium ion channel blockers, amlodipine and diltiazem, against human rotavirus infection.

Methods: Cytotoxic effects of the drugs on MA-104 cells were evaluated using the neutral red assay. The effects of amlodipine and diltiazem at non-toxic concentrations on human rotavirus were examined using cytopathic effect inhibition, TCID₅₀, and real-time PCR assays.

Results: The highest inhibitory effect was obtained at concentrations of 0.5 μg/ml of amlodipine and 3 μg/ml of diltiazem, leading to 4.6 and 5.5 logarithmic reductions in infectious rotavirus titer and four- and a five-fold increase in the C_t values compared to the virus control, respectively (p-value < 0.001). Conversely, infectious rotavirus titers were significantly elevated compared to the virus control at concentrations above 0.9 μg/ml of amlodipine and above 25 μg/ml of diltiazem.

Conclusion: Our study suggests that in addition to cardiovascular diseases, calcium channel blockers at their optimal doses may also be used to treat gastroenteritis caused by rotavirus infection.

Background: Blastocystis species (sp.) are enteric parasites that live in both humans' and animals' gastrointestinal tracts. Blastocystis hominis (B. hominis) is the recognizable human isolates in clinical and diagnostic specimens. Human infection occurs via the oro-fecal route, particularly in developing areas due to the lack of sanitation and hygienic facilities. B. hominis can exist in the large intestine for weeks to years until treated appropriately. Metronidazole is the drug of choice for the treatment of Blastocystis infection. However, it induces intolerable side effects and has been shown to have teratogenic and carcinogenic potential. Several medicinal plant extracts have been experimentally tested against Blastocystis infection in comparison to currently available treatments.

Objective: Based on in vitro and in vivo studies, this article reviewed anti-Blastocystis activity of some medicinal plants.

Methods: To conduct the research for this review, Google Scholar and PubMed were the primary search engines used to find relevant literature. A total of 19 published in vitro and in vivo studies were evaluated to identify the anti-Blastocystis effects of various medicinal plants.

Results: Multiplication of Blastocystis parasites as well as nucleic acids and protein synthesis, all be inhibited by extracts from different medicinal plants. These natural agents have been shown to be both safe and effective when compared to the existing treatment options.

Conclusion: Different medicinal plants can combat Blastocystis infection and could be a good substitute for metronidazole and other synthetic treatments.

Background: Acinetobacter baumannii is an opportunistic multidrugresistant, aerobic, glucose non-fermentative, and oxidative-negative coccobacilli bacteria. This life-threatening nosocomial infection is associated with immunocompromised patients.

Objective: This review aims to investigate the multiple drug resistance mechanisms and new emerging diagnostics & treatments for Acinetobacter baumannii.

Methods: All the articles that were most relevant to A. baumannii virulence and drug resistance mechanisms were founded by a literature search on PubMed. Google Patents were used to find discoveries related to diagnostics and treatment.

Results: Efflux pumps, β-lactamases, aminoglycosides, outer membrane proteins, and alteration of the target sites were identified in the Acinetobacter baumannii pathogen as the most prevalent drug resistance mechanisms. Gene detection, peptide detection, and antigen-antibody-associated detection were the latest diagnostics. Novel antimicrobial peptides, sterilization techniques using blue light, and combination therapies are being developed to effectively treat A. baumannii infections.

Conclusion: This review concludes that new drugs and formulations with high efficiency, low cytotoxicity, and no nephrotoxicity are in absolute need. In the near future, we can expect omics technology to play a significant role in discovering new drugs and potential targets.

Background: Credentials of molecular diagnostic approaches are an important goal. Since protein-protein interaction (PPI) network analysis is an apposite method for molecular valuation, a PPI grid related to Intrinsically Disordered Proteins (IDPs) of RA was targeted in the present research.

Aim: The aim of the study is to analyse the role of highly disordered proteins and their functional parameters in causing Rheumatoid Arthritis (RA).

Methods: Cytoscape software helped in identifying molecular interaction networks. Intrinsically disordered proteins lack higher order structure and have functional advantages, but their dysregulation can cause several diseases. All the significant proteins responsible for RA were identified. On the basis of the data obtained, highly disordered proteins were selected. Further, MSA was done to find the similarity among the highly disordered proteins and their functional partners. To determine the most relevant functional partner( s)/interacting protein(s) out of large network, three filters were introduced in the methodology.

Results: The two filtered proteins, IBSP and FGF2, have common functions and also play a vital role in the pathways of RA. Thus, gives an in-depth knowledge of molecular mechanisms involved in Rheumatoid Arthritis and targeted therapeutics.

Conclusion: The network analysis of these proteins has been explored using Cytoscape, and the proteins with favourable values of graph centrality parameters such as IBSP and FGF2 are identified. Interesting functional cross talk such as bio mineralization, boneremodelling, angiogenesis, cell differentiation, etc., of SPP1 with IBSP and FGF2 is found, which throws light into the fact that these two proteins play a vital role in the pathways of RA.

Vaccines are usually regarded as one of the most important tools in the battle against infectious diseases. Even though currently accessible vaccinations are an incredible success story in contemporary medicine and have had a significant impact on global morbidity and death rates, it is evident that current vaccine delivery approaches need to be improved. To allow the successful creation of vaccinations against contagious diseases that have proven challenging to manage with conventional procedures, improvements are necessary. Improvements could include the introduction of innovative injectable adjuvants or novel delivery methods, such as mucosal immunization. Protection against infections that infect mucosal areas may necessitate mucosal delivery. Alternatively, innovative techniques for delivery, such as intradermal administration using self-administrable devices or the use of microneedle technology to bypass the stratum corneum's skin penetration barrier and aid in the transport of antigens, could be utilized to increase vaccine compliance. Needle-free delivery systems are of particular relevance for safer mass immunization programs, as they would prevent problems caused by needles reuse in several regions of the world, as well as needle-stick accidents. Based on this information, future vaccine development will mainly concentrate on rational antigen, adjuvant, and, most importantly, delivery mechanism design, resulting in new and improved vaccinations. In addition, this study discusses the current state and prospects of vaccine delivery via a variety of channels, including non- or minimally invasive approaches.