Experimental Drug Research Articles

Application of Convolutional Neural Networks Using Action Potential Shape for In-Silico Proarrhythmic Risk Assessment.

This study proposes a convolutional neural network (CNN) model using action potential (AP) shapes as input for proarrhythmic risk assessment, considering the hypothesis that machine-learning features automatically extracted from AP shapes contain more meaningful information than do manually extracted indicators. We used 28 drugs listed in the comprehensive in vitro proarrhythmia assay (CiPA), consisting of eight high-risk, eleven intermediate-risk, and nine low-risk torsadogenic drugs. We performed drug simulations to generate AP shapes using experimental drug data, obtaining 2000 AP shapes per drug. The proposed CNN model was trained to classify the TdP risk into three levels, high-, intermediate-, and low-risk, based on in silico AP shapes generated using 12 drugs. We then evaluated the performance of the proposed model for 16 drugs. The classification accuracy of the proposed CNN model was excellent for high- and low-risk drugs, with AUCs of 0.914 and 0.951, respectively. The model performance for intermediate-risk drugs was good, at 0.814. Our proposed model can accurately assess the TdP risks of drugs from in silico AP shapes, reflecting the pharmacokinetics of ionic currents. We need to secure more drugs for future studies to improve the TdP-risk-assessment robustness.

Transcriptomic screening to identify hub genes and drug signatures for PCOS based on RNA-Seq data in granulosa cells

BackgroundPolycystic ovary syndrome (PCOS) is one of the most incident reproductive diseases, and remains the main cause of female infertility. Granulosa cells play a critical role in normal follicle development and steroid hormones synthesis. In spite of extensive research, no sole medication has been approved by FDA to treat PCOS. This study aimed to investigate the novel therapeutics targets in PCOS, focusing on granulosa cells transcriptome functional analysis with a drug repositioning approach. MethodsPCOS microarray and RNA-Seq datasets in granulosa cells were screened and reanalyzed. KEGG pathway enrichment and interaction network analyses were performed and followed by a set of drug signature screening and Poly-pharmacology survey. Results545 deregulated genes were identified via filters including padj < 0.05 and |log2FC| > 1. Amongst the top 15 KEGG pathways significantly enriched, metabolism of xenobiotics by cytochrome P450, steroid hormone biosynthesis and ovarian steroidogenesis were observed. The Protein-Protein Interaction network identified 18 hub genes amongst this set. Interestingly, most candidate drug signatures have been introduced by databases are either FDA approved or entered into clinical trials, including melatonin, resveratrol and raloxifene. Investigational or experimental introduced drugs obey rules of drug-likeness with almost safe and acceptable ADMET properties. Notably, 21 top target genes of the final drug set were also included in the granulosa significant differentially expressed genes. ConclusionResults of the current study represent approved, investigational and experimental drug signatures according to the differentially expressed genes in granulosa cells with supported literature reviews. This data might be useful for researchers and clinicians to pave the way for better management of PCOS.

The likelihood of being helped or harmed as a patient-centred tool to assess cyclin dependent kinase 4/6 inhibitors clinical impact and safety in metastatic breast cancer: a systematic review and sensitivity-analysis

In hormone-receptor positive/HER2-negative metastatic breast cancer (mBC) no randomized comparisons are available between CDK4/6 inhibitors. We undertook this systematic review and meta-analysis to assess the reliability of the likelihood of being helped or harmed (LHH). PubMed, CENTRAL, Embase and oncological meetings websites were searched to September 13th, 2022. We included phase III randomized controlled trials (RCTs) investigating palbociclib, ribociclib and abemaciclib in addition to endocrine therapy (ET) compared to placebo in hormone-receptor positive/HER2-negative advanced or mBC. Outcomes were progression-free survival (PFS), overall survival (OS), adverse events (AEs), dose reductions and discontinuations. Hazard ratios (HRs) and risk differences were computed with a random effect model to estimate the number needed to treat/harm (NNT/NNH). LHH was computed as (1/NNT)/(1/NNH). PROSPERO registration number: CRD42022362417. 2204 records were screened and seven RCTs (4415 patients) were included. A significant PFS benefit was observed in patients treated with a CDK4/6 inhibitor compared to placebo (HR 0.549; 0.508-0.594, I 2 =0). Palbociclib, ribociclib and abemaciclib had similar NNTs (4.4, 5.0 and 4.4). Palbociclib and ribociclib showed lower LHHs for grade 3-4 neutropenia (0.33 and 0.35) and febrile neutropenia ([FN], 14.27 and 15.52), while abemaciclib the lowest LHH for any grade diarrhea (0.42). Abemaciclib had a lower LHH for grade 3-4 fatigue (9.92) and the highest LHH for all grade 3-4 AEs (0.62), while ribociclib the lowest LHH (1.75) for grade 3-4 hepatotoxicity. Palbociclib had the highest LHH for dose reductions and discontinuations (0.65 and 6.17). Considering OS, an overall benefit was observed (HR 0.788, 0.727-0.856, I 2 =0%); ribociclib and abemaciclib had lower NNTs (9.7 and 10.0). Ribociclib showed the highest LHH for diarrhea (1.29), fatigue (7.37), dose reductions (0.28) and discontinuations (2.40), while abemaciclib the highest LHHs for neutropenia (0.40), FN (12.53) and hepatotoxicity (2.23). Palbociclib and ribociclib showed lower LHHs for haematological toxicities and abemaciclib for diarrhea. Palbociclib confirmed to be a manageable drug. The LHH appears to be a reliable synthesis tool for balancing risks and benefits of experimental drugs when head-to-head comparisons are missing. None.

Preclinical species gene expression database: Development and meta-analysis.

The evaluation of toxicity in preclinical species is important for identifying potential safety liabilities of experimental medicines. Toxicology studies provide translational insight into potential adverse clinical findings, but data interpretation may be limited due to our understanding of cross-species biological differences. With the recent technological advances in sequencing and analyzing omics data, gene expression data can be used to predict cross species biological differences and improve experimental design and toxicology data interpretation. However, interpreting the translational significance of toxicogenomics analyses can pose a challenge due to the lack of comprehensive preclinical gene expression datasets. In this work, we performed RNA-sequencing across four preclinical species/strains widely used for safety assessment (CD1 mouse, Sprague Dawley rat, Beagle dog, and Cynomolgus monkey) in ∼50 relevant tissues/organs to establish a comprehensive preclinical gene expression body atlas for both males and females. In addition, we performed a meta-analysis across the large dataset to highlight species and tissue differences that may be relevant for drug safety analyses. Further, we made these databases available to the scientific community. This multi-species, tissue-, and sex-specific transcriptomic database should serve as a valuable resource to enable informed safety decision-making not only during drug development, but also in a variety of disciplines that use these preclinical species.

IDENTIFICATION OF ANTI-CANCEROUS DRUGS FOR THE MUTATED SNAP25 PROTEIN RELATED TO BRAIN TUMOR THROUGH STRUCTURE-BASED VIRTUAL SCREENING APPROACH

Objective: Brain tumor is a formidable challenge for drug development, and drugs derived from many advanced technologies are being tested in clinical trials. Synaptosomal-associated protein of 25 kDa (SNAP25) is a membrane-binding protein in neurons and it is critical in neurotransmission for the fusion of plasma membrane and synaptic vesicle making it a prime target to address brain tumors. The SNAP-25 gene is responsible for personality disorders, schizophrenia, attention deficit, and hyperactivity disorder in human beings. It is recently discovered, that this protein is responsible for brain cancer as well. Methods: In the present research, 17 investigational and experimental anticancer drugs were selected from the PubChem and DrugBank databases to identify potential inhibitors with high stability to treat mutated SNAP25 protein. For this purpose, we have used the structure-based virtual screening technique wherein, the candidate molecules are computationally docked into the 3D structure of the biological. The docking was achieved in PyRx 0.8 software and the drugs were then ranked based on their predicted binding affinity or complementarity to the binding site. Results: Based on the ligand binding energy, the top six compounds having greater inhibitory effects towards SNAP25 were selected and then visualized with Pymol and Biovia visualizers. The compound Crenolanib has better pharmacological properties and demonstrated higher binding affinities with the target protein. Therefore, this Crenolanib docked confirmations were appraised for molecular dynamic simulations. Conclusion: The study concluded that the anticancer drug Crenolanib exerted inhibitory potential against the mutated protein SNAP-25 and therefore it can be exploited as a cancer modulator to address brain tumors.

Machine learning models to accelerate the design of polymeric long-acting injectables

Long-acting injectables are considered one of the most promising therapeutic strategies for the treatment of chronic diseases as they can afford improved therapeutic efficacy, safety, and patient compliance. The use of polymer materials in such a drug formulation strategy can offer unparalleled diversity owing to the ability to synthesize materials with a wide range of properties. However, the interplay between multiple parameters, including the physicochemical properties of the drug and polymer, make it very difficult to intuitively predict the performance of these systems. This necessitates the development and characterization of a wide array of formulation candidates through extensive and time-consuming in vitro experimentation. Machine learning is enabling leap-step advances in a number of fields including drug discovery and materials science. The current study takes a critical step towards data-driven drug formulation development with an emphasis on long-acting injectables. Here we show that machine learning algorithms can be used to predict experimental drug release from these advanced drug delivery systems. We also demonstrate that these trained models can be used to guide the design of new long acting injectables. The implementation of the described data-driven approach has the potential to reduce the time and cost associated with drug formulation development.

Reversible cerebral vasoconstriction syndrome: Considerable differential diagnosis

Background: Headache is the most common symptom in the neurology department of the hospital. This makes it a very important topic to understand more about what causes headaches. There are many causes of headaches and based on the cause, there could be different locations for headaches. One of the causes of the headache could be reversible vasoconstriction in the brain. This type of headache overlaps with a lot of differential diagnoses. Hence, it is important to bring light to this differential diagnosis to improvise the treatment regimen for the patient. Objectives: The objectives of the study were to study reversible cerebral vasoconstriction syndrome (RCVS) and all the differential diagnosis of headache that overlaps with RCVS. Methods: We searched the recent studies done on RCVS along with meta-analysis, controlled clinical trials, and cohort studies. We made the differential tables with symptoms, diagnoses, and treatments to bring a better understanding of the overlapping symptoms of different diseases and RCVS. Result: Understanding the symptoms, diagnosis of RCVS, and other overlapping symptoms of diseases, is helpful to avoid the extra expenditure of the patient. It would also help in leading treatment in the right direction without putting the patient on the experimental drugs.

Computer-aided design of a cyclic di-AMP synthesizing enzyme CdaA inhibitor.

Cyclic di-AMP (c-di-AMP) is an essential secondary messenger regulating cell wall homeostasis and myriads of physiological processes in several Gram-positive and mycobacteria, including human pathogens. Hence, c-di-AMP synthesizing enzymes (DACs) have become a promising antibacterial drug target. To overcome a scarcity of small molecule inhibitors of c-di-AMP synthesizing enzyme CdaA, a computer-aided design of a new compound that should block the enzyme has been performed. This has led to the identification of a molecule comprising two thiazole rings and showing inhibitory potential based on ITC measurements. Thiazole scaffold is a good pharmacophore nucleus known due to its various pharmaceutical applications. It is contained in more than 18 FDA-approved drugs as well as in dozens of experimental drugs. Hence, the designed inhibitor can serve as a potent lead compound for further development of inhibitor against CdaA.

Social Rights in Comparative Constitutional Law: Right to Health in the Perspective of the Brazilian and German Constitutional Courts

This article deals specifically with the current phenomenon of the judicialisation of social rights in Brazilian and German Constitutional Courts, taking as practical example the right to health. A progressive increase in the number of lawsuits in Brazil involving health insurance plans, expensive and experimental medicines and hospital admissions has been noted in the last years. The main obstacles to the judicial realization of social rights in Brazil are the alleged violation of the principle of separation of powers – branches of state – for decisions regarding the allocation of public financial resources, the absence of a previously prepared public policy and the impossibility of universalizing social demands due to economic-financial limitations. Nevertheless, the legal categories of the ’existential minimum’ and the ‘duty of progressivity’ have been used in the most recent decisions of the Brazilian Supreme Court as a way of realising social rights under strong influence of the German Federal Constitutional Court and international human rights law. Finally, the situation of Brazil before the Inter-American Court of Human Rights regarding the implementation of social rights in a structural context of exclusion and poverty is analysed.

Nilotinib: from animal-based studies to clinical investigation in Alzheimer's disease patients.

Nilotinib: from animal-based studies to clinical investigation in Alzheimer's disease patients.

The effect of food intake on the tolerance of mono- and combined anti-tb drugs in a toxicological experiment

The experiments revealed a decrease in the toxic effects of anti-tuberculosis drugs when taking drugs after eating. The introduction of ethambutol before meals reduced its toxicity and increased the life expectancy of rats when ethambutol was administered in combination with isoniazid. With the introduction of anti-tuberculosis drugs after a meal in well-fed rats, an increase in the average life expectancy was revealed only with the introduction of ethambutol and combined anti-TB drugs.

Антибактериальная активность экспериментального коктейля бактериофагов против патогенной микробиоты наружных слуховых проходов собак и кошек

Otitis externa is a common pathological condition of small pets requiring antimicrobial therapy. Widespread unjustified use of antibiotics exacerbates the existing problem of antibiotic resistance, and the number of isolates with multidrug resistance (MDR) is increasing. In this regard, an actual task is to search and evaluate alternative methods of antimicrobial therapy, for example, bacteriophages. In this study, the antibacterial activity of an experimental bacteriophage-based drug was evaluated against current participants in the etiopathogenesis of otitis externa in dogs and cats: Staphylococcus pseudintermedius, Staphylococcus aureus, Streptococcus pyogenes, Staphylococcus schleiferi subsp. Coagulans, Staphylococcus hyicus, Pseudomonas aeruginosa, Escherichia coli, Streptococcus canis, Enterococcus faecalis. The bacteriophage-based drug showed expressed antibacterial efficacy in vitro. When diluted 128 times, the cocktail of bacteriophages stably lysed test cultures of bacteria. There is a need for constant search and expansion of the number of virulent strains of bacteriophages to create an experimental means for the treatment of external otitis externa in dogs and cats, nevertheless, due to the positive results of the studies conducted, the actual potential of bacteriophages as an alternative to antibiotic therapy for pathologies of the external auditory canal in small pets is confirmed.

A modified mouse model of haemorrhagic transformation associated with tPA administration after thromboembolic stroke

ObjectiveTo establish a new mouse model of haemorrhagic transformation associated with delayed tissue-type plasminogen activator (tPA) treatment to provide a novel tool to study therapeutic strategies for haemorrhagic transformation. MethodsMale C57BL/6 mice were subjected to carotid artery thrombosis stimulated with ferric chloride. The thrombus was then mechanically detached to induce migration toward the intracranial circulation. To induce haemorrhagic transformation, mice were intravenously injected with 10 mg/kg tPA 4.5 h after the onset of ischaemia and were sacrificed 24 h after tPA treatment. ResultsIn this new model, administration of tPA 4.5 h after stroke exacerbated the risk of intracerebral haemorrhage. Thrombolysis with tPA also exacerbated cerebral infarction, brain oedema, blood–brain barrier breakdown, and neurological deficits. However, cerebral blood flow was not significantly affected. ConclusionThe present model is reproducible, easy to perform, and mimics the clinical situation of haemorrhagic transformation after tPA treatment in humans. This modified model can be used as a new tool to test experimental drugs for haemorrhagic transformation associated with delayed tPA administration after an ischaemic stroke.

ИССЛЕДОВАНИЕ IN SILICO АФФИННОСТИ РИВАРОКСАБАНА К ГЛЮКОКИНАЗЕ

Type 2 diabetes mellitus is an urgent problem of health care. Comparison of the structure of the Rivaroxaban with the structure of a number of experimental drugs, which are Glucokinase activators, revealed the perspectives of its evalua-tion in the drug design for the treatment of type 2 diabetes. In in silico experi-ments, the interaction of Rivaroxaban with glucokinase, which is involved in glu-cose phosphorylation in liver and pancreas cells, has been studied. Using molecu-lar docking methods, complexes of Rivaroxaban with a protein in the allosteric center responsible for the action of glucokinase activators, were generated: the minimum binding energy was found 9.41 kcal/mol. The results obtained in the experiment in silico open the perspectives of design and development of the new effective antidiabetic drugs as well as investigation of the concomitant action of the anticoagulant Rivaroxaban.

Enhancing the efficacy of anti-malarial drugs with immune boosters: A mathematical model

&lt;abstract&gt; &lt;p&gt;This paper presents a mathematical model of severe malarial anemia (SMA), which is a complication of malaria and is a major contributor to malaria-related deaths. SMA is characterized by a decrease in hemoglobin levels in the blood due to the suppression of red blood cell (RBC) recruitment by the protein macrophage migration inhibitory factor (MIF). Plasmodium falciparum, which is a malaria-causing parasite, secretes a specific form of MIF called plasmodium falciparum macrophage migration inhibitory factor (PFMIF), which affects immune cells. Artesunate, which is the primary treatment for SMA, reduces the parasite level but does not increase hemoglobin levels and can sometimes lead to hemolytic anemia, which requires a blood transfusion. To address this issue, the experimental drug Epoxyazadiradione (Epoxy) was explored as a potential treatment for SMA. Epoxy inhibits both MIF and PFMIF interactions with immune cells and has the potential to increase hemoglobin levels in SMA patients. Our model simulations support previous findings that the appropriate combination of Artesunate with Epoxy can reduce parasite load while preventing anemia by maintaining hemoglobin levels at an adequate level. Additionally, we explored the impact of immune boosters on the anti-malarial drugs Artesunate and Epoxy and discovered that an insufficient amount of drugs is ineffective, while an excessive amount may not be beneficial.&lt;/p&gt; &lt;/abstract&gt;

Susceptibility analysis of mutations that confer resistance to inhibitors of the SARS-CoV-2 main protease (Mpro) and RNA-dependent RNA polymerase (RdRp)

Enormous efforts have been made worldwide to generate therapeutic options to prevent the transmissibility of SARS-CoV-2 and reduce its replication in humans. Currently, the emergence of new variants of the virus is of great concern because the evolution of the viral genome and the inherent mutations introduced in the viral proteins could decrease the effectiveness of the first-line therapeutic agents used to prevent and treat COVID-19. The present study evaluated the susceptibility of two important pharmacological drug targets of SARS-CoV-2, the major protease (Mpro) and the RNA-dependent RNA polymerase (RdRp), to suffer point mutations that could produce resistance to inhibitors of these enzymes. The results showed that the residues that contour the inhibitor binding site in RdRp are extremely conserved between the different RNA virus species. This suggests the RdRp enzyme has a low probability to suffer mutation that could confer resistance to therapeutic drugs, such as Remdesivir, an FDA approved compound to treat COVID-19. In contrast, we observed that the Mpro enzyme could undergo up to ten-point mutations in the active site, which is the binding site of several experimental drugs under development, such as Carmofur and N3. Molecular docking analysis showed that the presence of single point mutations in the Mpro active site produces an increase in the binding affinity of carmofur, probably due to the small size and high flexibility of this molecule. However, the Pro168Ser and Ala191Val mutations significantly decrease the affinity of N3 binding to Mpro, suggesting the possible emergence of resistance to this drug. These results could help to anticipate the effect of different mutations on the way Mpro inhibitors bind to the enzyme, and design new inhibitors that address the effect of resistance.

CRAC (Clinical Relevance of Alterations in Cancer): a Knowledge Base for the Selection of Molecularly Matched Therapy for Solid Tumors.

Multigene testing using NGS (next-generation sequencing) provides a large amount of information and can detect multiple molecular alterations. Subsequent clinical interpretation is a time-consuming process necessary to select a treatment strategy. Existing databases often contain inconsistent information and are not regularly updated. The use of ESCAT levels of evidence requires a deep understanding of the nature of alterations and does not answer the question of which therapy option to select when multiple biomarkers with the same level of evidence are detected. To address these issues, we created the Clinical Relevance of Alterations in Cancer (CRAC) database on the relevance of detected alterations in specific genes, which are often analyzed as part of NGS panels. The team of oncologists and biologists assigned a CRAC score from 1 to 10 to each biomarker (a type of genomic alteration characteristic of specific genes) for 15 malignancies; an average score was entered into the database. CRAC scores are a numerical reflection of the following factors: therapy availability and the prospects of drug treatment with experimental drugs for patients with a particular type of tumor. A total of 134 genes and 15 of the most common tumor types have been selected for CRAC. The biomarker-nosology associations with CRAC scores in the range of 1-3 are the most frequent (n=2719 out of 3495; 77.8%), the least frequent ones (n=52 out of 3495; 1.5%) are with the highest CRAC scores 9 and 10. To estimate the practical effectiveness of the CRAC database, 208 reports on comprehensive molecular profiling were retrospectively analyzed; the applicability of CRAC was compared with the ESCAT level of evidence system. The highest CRAC scores corresponded to the ESCAT maximum levels of evidence: the range of scores 8-10 corresponded to evidence levels I and II. No biomarker within the same level of evidence was represented by the same CRAC score; the largest range of CRAC scores was observed for biomarkers of levels evidence IIIA and IV - from 2 to 10 and from 1 to 9, respectively. The use of CRAC scores allowed to identify additional 95 alterations with CRAC scores of 1-5 in the studied patients. The developed database is available at: https://crac.oncoatlas.ru/.

‘NanoViroSan’ antimicrobial composite, designed for emergency epizootic situations and safe usage in ecological pig farming

Analytical data of preclinical and clinical trials of the experimental veterinary composite drug ‘NanoViroSan’ (containing Methisazone, Silgeran and magnesium nanooxide) on laboratory models of Aujeszky’s (AD) and Teschen (TD) diseases, circovirus infections (PCV 2) and actinobacillary pleuropneumonia (APP) as well as in enzootic foci of mixed infection of AD-PCV-APP and swine pox, are presented, respectively. At the level of statistical probability p ≤ 0.01–0.03 (n = 88), the absence of cytotoxic (n = 40, cultures of pig testicle cells and pig alveolar macrophages) and biotoxic effects (n = 48 guinea pigs) was proven, as well as high antimicrobial (viro- and bacteriostatic) activity of the drug in the concentration range (by Methisazone) of 1.0–4.0 mg/cm3. Intramuscular administration of the drug to male pedigree piglets in doses of 0.5 cm3/20 kg and 1.5 cm3/20 kg three times with an interval of a day made it possible to stop the carriage of the causative agents of mixed infection in the conditions of pig-breeding (n = 26, p ≤ 0.02). Similar treatment with the drug in a dose of 2 cm3/20 kg (by Methisazone) of a boar and five sows in another commodity farm made it possible to break the chain of vertical transmission of the causative agent of swine pox from the nucleus to offspring of the herd (n = 227, p ≤ 0.03). There conclusion was made regarding the perspective of experimental drug for bioprotection of pig farming in the conditions of martial law, as well, if additional research will be positive — as for the development of permaculture (‘green technologies’) in the field of pig breeding

Corn‐like mSiO2@ZIF‐8 Composite Load with Curcumin for Target Cancer Drug‐Delivery System

AbstractTo improve the drug loading rate of mesoporous silica (mSiO2), mSiO2 nanorods were synthesized by a modified sol‐gel method, then mSiO2@ZIF‐8 nanoparticles were prepared by using mSiO2 nanorods as the matrix. The structure of mSiO2 and mSiO2@ZIF‐8 were characterized. The results show that mSiO2@ZIF‐8 nanoparticles are corn‐like, with a specific surface area of 116.81 m2 g−1, pore volume of 0.31 cm3 g−1, and pore size of 8.43 nm. Curcumin (CUR) was used as an anti‐tumor model drug in drug delivery experiments. The drug loading rate of mSiO2@ZIF‐8 for CUR is 21.39 %. Before modification by Chitosan (CS) and folic acid (FA), the cumulative release rate of CUR is 30.27 % at pH 5.6 and 26.26 % at pH 7.4. After been target functionalized by CS and FA. At pH 5.6 and pH 7.4, the cumulative release rates are 34.21 % and 20.48 %, respectively, within 228 h after drug release in vitro. The results show that the drug delivery system has good pH responsiveness. Zero‐order, first‐order, Higuchi, Hixson Crowell, and Korsmeyer Peppas models were used to describe the release kinetics of mSiO2@ZIF‐8@CUR. The Higuchi model provides the highest fit for the CUR release of mSiO2@ZIF‐8@CUR.

Real World Effectiveness of Benzydamine + Chlorhexidine on Sore Throat of COVID-19 Patients (Difflam-C® COVID-19)

Objective: Severe acute respiratory syndrome coronavirus 2 caused a global pandemic with staggering speed. Various experimental drugs and non-pharmacologic interventions had been investigated to determine additional benefits for the management of COVID-19. This study explored the real-world effectiveness of benzydamine + chlorhexidine (Difflam-C®) solution in alleviating sore throat of Filipino patients, under condition of routine medical practice. Study Design: Observational, uncontrolled study design Setting: Ambulatory / out-patient health facilities Method: This study included patients who were suspect, probable and confirmed to have COVID-19 who manifested with symptoms and signs of dysphagia / odynophagia. They were prescribed with benzydamine + chlorhexidine (Difflam-C®) solution as a supplement for the management of these conditions, regardless of RT-PCR and/or rapid antigen test result, in accordance with the respective local prescribing information and routine clinical practice. Results: A decreasing trend can be observed in the median visual analogue scales (VAS) pain scores from baseline up to seven days. The difference from the baseline VAS score was significant in all observation period from day 1 to day 7 (p&lt;0.001). The greatest difference was seen between days 4 and 5 (median VAS scores of 2 and 0, respectively). Almost all of the participants (95.9%) reported sore throat resolution at the end of the seventh day of observation. Majority did not experience adverse events and if so, were generally mild. Conclusion: The benzydamine + chlorhexidine (Difflam-C®) gargle alleviated the signs of dysphagia and odynophagia among patients with suspected, probable and confirmed COVID-19 infection