Influence of endodontic access cavity design on mechanical properties of a first mandibular premolar tooth: a finite element analysis study.

OBJECTIVES: This study aimed to investigate the influence of access cavity designs on the mechanical properties of a single-rooted mandibular first premolar tooth under various static loads using a finite element analysis. MATERIALS AND METHODS: 3-dimensional FEA designs were modeled according to the access cavity designs: an intact tooth (control), traditional access cavity (TEC-I), traditional access cavity with Class-II mesio-occlusal cavity design (TEC-II), conservative access cavity (CEC), ninja access cavity (NEC), caries-driven access cavity (Cd-EC), buccal access cavity (BEC) and bucco-occlusal access cavity (BOEC). After the simulated access cavity preparations, root canal treatment was simulated and three different static loads which mimicked oblique and vertical mastication forces were applied to the models. The stress distribution and maximum Von Misses stress values were recorded. The maximum stress values were obtained on both enamel and dentin under multi-point vertical loads. RESULTS: The maximum stress values were obtained on both enamel and dentin under multi-point vertical loads. Under all load types, the minimum stress distribution was observed in the control group, followed by CEC, NEC and BEC designs. The highest stress concentration was detected in Cd-EC and TEC-II designs. Under single-point vertical loading, the stress was mostly concentrated in the lingual PCD area, while under multi-point vertical loading, the entire root surface was stress-loaded except for the lingual apical third of the root. CONCLUSION: Preserving tooth tissue by simulating CEC, NEC and BEC access cavities increased the load capacity of a single-rooted mandibular first premolar following simulated endodontic treatment.

Artificial intelligence in endodontics: Data preparation, clinical applications, ethical considerations, limitations, and future directions.

Artificial intelligence (AI) is emerging as a transformative technology in healthcare, including endodontics. A gap in knowledge exists in understanding AI's applications and limitations among endodontic experts. This comprehensive review aims to (A) elaborate on technical and ethical aspects of using data to implement AI models in endodontics; (B) elaborate on evaluation metrics; (C) review the current applications of AI in endodontics; and (D) review the limitations and barriers to real-world implementation of AI in the field of endodontics and its future potentials/directions. The article shows that AI techniques have been applied in endodontics for critical tasks such as detection of radiolucent lesions, analysis of root canal morphology, prediction of treatment outcome and post-operative pain and more. Deep learning models like convolutional neural networks demonstrate high accuracy in these applications. However, challenges remain regarding model interpretability, generalizability, and adoption into clinical practice. When thoughtfully implemented, AI has great potential to aid with diagnostics, treatment planning, clinical interventions, and education in the field of endodontics. However, concerted efforts are still needed to address limitations and to facilitate integration into clinical workflows.

Artificial intelligence in endodontics: Fundamental principles, workflow, and tasks.

The integration of artificial intelligence (AI) in healthcare has seen significant advancements, particularly in areas requiring image interpretation. Endodontics, a specialty within dentistry, stands to benefit immensely from AI applications, especially in interpreting radiographic images. However, there is a knowledge gap among endodontists regarding the fundamentals of machine learning and deep learning, hindering the full utilization of AI in this field. This narrative review aims to: (A) elaborate on the basic principles of machine learning and deep learning and present the basics of neural network architectures; (B) explain the workflow for developing AI solutions, from data collection through clinical integration; (C) discuss specific AI tasks and applications relevant to endodontic diagnosis and treatment. The article shows that AI offers diverse practical applications in endodontics. Computer vision methods help analyse images while natural language processing extracts insights from text. With robust validation, these techniques can enhance diagnosis, treatment planning, education, and patient care. In conclusion, AI holds significant potential to benefit endodontic research, practice, and education. Successful integration requires an evolving partnership between clinicians, computer scientists, and industry.

Propolis Use in Dentistry: A Narrative Review of Its Preventive and Therapeutic Applications.

Propolis is a resinous substance produced naturally by bees, and it consists of the exudates of plants mixed with enzymes, wax, and pollen. Propolis continues to gain considerable scientific interest due to its potential health benefits. The modern-day use of propolis in pharmaceutical preparations, such as toothpastes, mouthwashes, chewable tablets, mucoadhesive gels, and sprays, is increasing. However, the effectiveness of using propolis-containing pharmaceuticals in dentistry is not clear. The present paper aims to review the literature on the dental applications of propolis in preventive dentistry, periodontics, oral medicine, and restorative dentistry and discuss its clinical effectiveness. A literature search was conducted using Scopus, PubMed, and Web of Science databases. In total, 104 studies were included, of which 46 were laboratory studies, 5 animal studies, and 53 human clinical studies. Overall, the laboratory studies revealed a range of antimicrobial effects of propolis on oral pathogens. Clinical investigations of propolis in biofilm and dental caries control as well as adjuvant periodontal therapies reported positive outcomes in terms of plaque control, pathogenic microbial count reduction, and periodontal tissue inflammation control. Additional investigations included the use of propolis for the management of recurrent aphthous stomatitis, oral mucositis, and cavity disinfection after caries removal as well as the development of a range of restorative dental materials. Based on the reported outcomes of the studies, the clinical usage of propolis has potential. However, the majority of the evidence is derived from studies with flaws in their methodological design, making their results and conclusions questionable. As a consequence, properly designed and well-reported clinical studies are required to affirm the effectiveness of propolis for dental applications. Additionally, the safety of propolis and the optimal concentrations and extraction methods for its clinical use warrant further investigation. Utilisation of standardised propolis extracts will help in quality control of propolis-based products and lead to the achievement of reproducible outcomes in research studies.

A laboratory study comparing the static navigation technique using a bur with a conventional freehand technique using ultrasonic tips for the removal of fibre posts.

AIM: There are currently no high-quality studies comparing the static navigation technique with conventional methods of fibre post removal. The aim of this ex vivo study was to compare the effectiveness of fibre post removal between a static navigation technique and a conventional freehand technique using ultrasonics by experienced and inexperienced operators. METHODOLOGY: Forty-eight extracted single-rooted human premolars were root-filled. A fibre post was cemented in all 48 teeth, which were then divided randomly into the following groups: static navigation group using burs; static navigation-ultrasonic group; and non-guided group using ultrasonic tips. The following parameters were evaluated for both experienced operators and inexperienced operators: reaching the gutta-percha root filling successfully, the time required to remove the entire post, the occurrence of lateral root perforations, and the amount of root dentine removed. The Kolmogorov-Smirnov test was used to examine the normality of the data; the anova test was used to compare the significant differences among groups; and Tukey tests were used for all two-by-two comparisons. The significance level was set at 0.05. RESULTS: In the static navigation group, the gutta-percha was reached significantly more frequently than in the non-guided group (p < .05). The static navigation approach required significantly less time than the non-guided approach to reach the gutta-percha (p < .05). The total removal of posts was significantly different between groups (p < .05), but there was no significant difference between experienced and inexperienced operators in the static navigation group (p > .05). More perforations were associated with the non-guided group than with the other two groups. The total mean loss of dentine in the non-guided group in all directions was 0.39 (±0.17) mm, with 0.25 (±0.09) mm for experienced, and 0.42 (±0.16) mm for inexperienced operators. CONCLUSION: When compared to a conventional ultrasonic technique for the removal of fibre posts, the static navigation method using burs resulted in less dentine removal, more rapid access to the gutta-percha root filling, less overall time to remove the posts, and fewer complications. When using static navigation, there was no difference in performance between experienced and inexperienced operators.

The Study and Relevance of Pulp Chamber Anatomy in Endodontics - A Comprehensive Review.

With the ever-increasing understanding of tooth anatomy, there is a renewed focus on the pulp chamber as an important component of the root canal system. For example, the pulp chamber is of critical relevance during diagnostic procedures such as pulp sensibility tests, deep caries removal, vital pulp treatments, access cavity preparation, tooth whitening, tooth restoration as well as methods for examining the floor of the pulp chamber to aid the detection of root canal orifices or the presence of perforations and cracks. The more recent concept of minimal invasive endodontics has also created a need to understand better the anatomy of the pulp chamber. The purpose of this article is to discuss the research methods used to study pulp chamber anatomy and the significance of the pulp chamber in endodontic research and clinical practice. In addition, directions for future research are emphasised.

Validity and reliability of artificial intelligence chatbots as public sources of information on endodontics.

AIM: This study aimed to evaluate and compare the validity and reliability of responses provided by GPT-3.5, Google Bard, and Bing to frequently asked questions (FAQs) in the field of endodontics. METHODOLOGY: FAQs were formulated by expert endodontists (n = 10) and collected through GPT-3.5 queries (n = 10), with every question posed to each chatbot three times. Responses (N = 180) were independently evaluated by two board-certified endodontists using a modified Global Quality Score (GQS) on a 5-point Likert scale (5: strongly agree; 4: agree; 3: neutral; 2: disagree; 1: strongly disagree). Disagreements on scoring were resolved through evidence-based discussions. The validity of responses was analysed by categorizing scores into valid or invalid at two thresholds: The low threshold was set at score ≥4 for all three responses whilst the high threshold was set at score 5 for all three responses. Fisher's exact test was conducted to compare the validity of responses between chatbots. Cronbach's alpha was calculated to assess the reliability by assessing the consistency of repeated responses for each chatbot. RESULTS: All three chatbots provided answers to all questions. Using the low-threshold validity test (GPT-3.5: 95%; Google Bard: 85%; Bing: 75%), there was no significant difference between the platforms (p > .05). When using the high-threshold validity test, the chatbot scores were substantially lower (GPT-3.5: 60%; Google Bard: 15%; Bing: 15%). The validity of GPT-3.5 responses was significantly higher than Google Bard and Bing (p = .008). All three chatbots achieved an acceptable level of reliability (Cronbach's alpha >0.7). CONCLUSIONS: GPT-3.5 provided more credible information on topics related to endodontics compared to Google Bard and Bing.

Critical analysis of a new system to classify root and canal morphology - A systematic review.

A novel system to classify root and canal morphology was recently introduced (Ahmed et al. 2017). This systematic review aimed to answer the following research question: Does the Ahmed et al. system provide a more accurate and practical classification of root and canal anatomy compared to other classifications? A literature search was conducted in Google Scholar, Scopus and Wiley Online Library to identify the citation counts for the article entitled 'A new system for classifying root and root canal morphology; doi.org/10.1111/iej.12685'. After removal of duplicates and unrelated articles, 15 studies were included and analysed. All studies compared the Ahmed et al. system with the Vertucci classification. Results revealed that both systems were able to classify simple canal configurations in single-rooted anterior and premolar teeth, disto-buccal and palatal roots of maxillary molars. However, the Ahmed et al. system provided more accurate and comprehensive categorisations of single-rooted teeth with complex canal anatomy, multi-rooted maxillary and mandibular premolars and the mesio-buccal root of maxillary molars. Further evidence on the utility of the Ahmed et al. system is required using other diagnostic devices especially in molars.

Critical analysis of the reporting quality of animal studies within Endodontics using the Preferred Reporting Items for Animal Studies in Endodontics (PRIASE) 2021 quality standard checklist.

AIM: To critically evaluate the reporting quality of a random sample of animal studies within the field of endodontics against the Preferred Reporting Items for Animal Studies in Endodontics (PRIASE) 2021 checklist and to investigate the association between the quality of reporting and several characteristics of the selected studies. METHODOLOGY: Fifty animal studies related to endodontics were randomly selected from the PubMed database with publication dates from January 2017 to December 2021. For each study, a score of '1' was given when the item of the PRIASE 2021 checklist was fully reported, whereas a score of '0' was given when an item was not reported; when the item was inadequately or partially reported, a score of '0.5' was given. Based on the overall scores allocated to each manuscript, they were allocated into three categories of reporting quality: low, moderate and high. Associations between study characteristics and reporting quality scores were also analysed. Descriptive statistics and Fisher's exact tests were used to describe the data and determine associations. The probability value of .05 was selected as the level of statistical significance. RESULTS: Based on the overall scores, four (8%) and 46 (92%) of the animal studies evaluated were categorized as 'High' and 'Moderate' reporting quality, respectively. A number of items were adequately reported in all studies related to background (Item 4a), relevance of methods/results (7a) and interpretation of images (11e), whereas only one item related to changes in protocol (6d) was not reported in any. No associations were confirmed between reporting quality scores and number of authors, origin of the corresponding author, journal of publication (endodontic specialty vs. non- specialty), impact factor or year of publication. CONCLUSIONS: Animal studies published in the specialty of endodontics were mostly of 'moderate' quality in terms of the quality of reporting. Adherence to the PRIASE 2021 guidelines will enhance the reporting of animal studies in the expectation that all future publications will be high quality.

Broad human and animal coronavirus neutralisation by SARS-CoV-2 S2-targeted vaccination

Several common-cold coronaviruses (HCoVs) are endemic in humans and several variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged during the current Coronavirus disease 2019 (COVID-19) pandemic. Whilst antibody cross-reactivity with the Spike glycoproteins (S) of diverse coronaviruses has been documented, it remains unclear whether such antibody responses, typically targeting the conserved S2 subunit, contribute to or mediate protection, when induced naturally or through vaccination. Using a mouse model, we show that prior HCoV-OC43 S immunity primes neutralising antibody responses to otherwise subimmunogenic SARS-CoV-2 S exposure and promotes S2-targeting antibody responses. Moreover, mouse vaccination with SARS-CoV-2 S2 elicits antibodies that neutralise diverse animal and human alphacoronaviruses and betacoronaviruses in vitro, and protects against SARS-CoV-2 challenge in vivo. Lastly, in mice with a history of SARS-CoV-2 Wuhan-based S vaccination, further S2 vaccination induces stronger and broader neutralising antibody response than booster Wuhan S vaccination, suggesting it may prevent repertoire focusing caused by repeated homologous vaccination. The data presented here establish the protective value of an S2-targeting vaccine and support the notion that S2 vaccination may better prepare the immune system to respond to the changing nature of the S1 subunit in SARS-CoV-2 variants of concern (VOCs), as well as to unpredictable, yet inevitable future coronavirus zoonoses.

Application of a new System for Classifying Root and Canal Anatomy in Clinical Practice - Explanation and Elaboration.

Adequate understanding and accurate characterization of normal and unusual root and canal morphology are essential requirements for successful root canal treatment. A new coding system for classifying root and canal morphology, accessory canals and anomalies has been introduced. In addition to technological advances related to experimental studies involving micro-computed tomography, the continuing clinical advances in magnification, illumination, imaging and intra-operative root canal treatment procedures have allowed clinicians to identify an increasingly wide range of anatomical variations in roots and canals in an attempt to achieve more predictable clinical outcomes. This review aims to provide a step-by-step explanation for the clinical application of the new coding system in dental practice, and to describe the anatomical variations in roots and canals for teeth scheduled for root canal treatment.

PRILE 2021 guidelines for reporting laboratory studies in Endodontology: explanation and elaboration.

Guidance to authors is needed to prevent their waste of talent, time and resources in writing manuscripts that will never be published in the highest-quality journals. Laboratory studies are probably the most common type of endodontic research projects because they make up the majority of manuscripts submitted for publication. Unfortunately, most of these manuscripts fail the peer-review process, primarily due to critical flaws in the reporting of the methods and results. Here, in order to guide authors, the Preferred Reporting Items for study Designs in Endodontology (PRIDE) team developed new reporting guidelines for laboratory-based studies: the Preferred Reporting Items for Laboratory studies in Endodontology (PRILE) 2021 guidelines. The PRILE 2021 guidelines were developed exclusively for the area of Endodontology by integrating and adapting the modified CONSORT checklist of items for reporting in vitro studies of dental materials and the Clinical and Laboratory Images in Publications (CLIP) principles. The process of developing the PRILE 2021 guidelines followed the recommendations of the Guidance for Developers of Health Research Reporting Guidelines. The aim of the current document is to provide authors with an explanation for each of the items in the PRILE 2021 checklist and flowchart with examples from the literature, and to provide advice from peer-reviewers and editors about how to solve each problem in manuscripts prior to their peer-review. The Preferred Reporting Items for study Designs in Endodontology (PRIDE) website (http://pride-endodonticguidelines.org/prile/) provides a link to the PRILE 2021 explanation and elaboration document as well as to the checklist and flowchart.

PRILE 2021 guidelines for reporting laboratory studies in Endodontology: A consensus-based development.

Reproducible, skilfully conducted and unbiased laboratory studies provide new knowledge, which can inform clinical research and eventually translate into better patient care. To help researchers improve the quality and reproducibility of their research prior to a publication peer-review, this paper describes the process that was followed during the development of the Preferred Reporting Items for Laboratory studies in Endodontology (PRILE) 2021 guidelines and which used a well-documented consensus-based methodology. A steering committee was created with eight individuals (PM, RO, OP, IR, JS, EP, JJ and SP), plus the project leaders (PD, VN). The steering committee prepared an initial checklist by combining and adapting items from the modified Consolidated Statement of Reporting Trials checklist for reporting in vitro studies of dental materials and the Clinical and Laboratory Images in Publications principles as well as adding several new items. The steering committee then formed a PRILE Delphi Group (PDG) and PRILE Online Meeting Group (POMG) to provide expert advice and feedback on the initial draft checklist and flowchart. The members of the PDG participated in an online Delphi process to achieve consensus on the items within the PRILE 2021 checklist and the accompanying flowchart for clarity and suitability. The PRILE checklist and flowchart developed by the online Delphi process were discussed further by the POMG. This online meeting was conducted on 12 February 2021 via the Zoom platform. Following this meeting, the steering committee developed a final version of the PRILE 2021 guidelines and flowchart, which was piloted by several authors when writing up a laboratory study for publication. Authors are encouraged to use the PRILE 2021 guidelines and flowchart to improve the clarity, completeness and quality of reports describing laboratory studies in Endodontology. The PRILE 2021 checklist and flowchart are freely available and downloadable from the Preferred Reporting Items for study Designs in Endodontology website (http://pride-endodonticguidelines.org/prile/).

Revitalizing previously treated teeth with open apices: A case report and a literature review.

Revitalizing the root canals of previously treated teeth with open apices is appealing to clinicians and patients. However, there are fundamental differences in the microbiome and the microenvironment between a canal with a primary endodontic infection and a canal with a persistent endodontic infection. The aims of this report are to report a case where a previously treated tooth with an open apex and a large apical radiolucency was treated successfully using regenerative endodontic treatment (RET) and to review and critically appraise the literature on procedures and outcomes of RET that result in revitalization of canal(s) in previously treated teeth with open apices. A maxillary central incisor with poor-quality root filling, a large apical radiolucency and an open apex was retreated using RET using platelet-rich fibrin as the scaffold. After 24 months, there was complete healing of the periapical lesion and obvious radiographic signs of apical root closure. Electronic searches were performed in MEDLINE, Scopus and Embase, and the baseline, procedural and outcome data of qualified articles were collected. An assessment tool was developed to rate the quality of evidence reported in these case report/series. Nine articles, three case series and six case reports, with a total of 17 teeth of all types, were included in the reports identified. The age of patients ranged from 7 to 48 years (mean: 19.4 years). The recall period ranged from 12 to 72 months (mean: 29 months). All 17 teeth survived and were functional with healing/healed outcomes. "Apical closure" was the most common radiographic finding regarding root development. The quality of evidence using the new assessment tool was rated "Excellent" in three case reports but only "Fair" in the other six articles. The present case report, as well as the review of the literature, suggests that revitalizing the root canal system of teeth with open apices and post-treatment disease using RET is a potentially valid treatment option. However, more clinical studies with higher levels of evidence and higher quality of evidence are required to confirm the viability of this treatment approach.

Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of nsp5 Main Protease

The coronavirus 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), spread around the world with unprecedented health and socio-economic effects for the global population. While different vaccines are now being made available, very few antiviral drugs have been approved. The main viral protease (nsp5) of SARS-CoV-2 provides an excellent target for antivirals, due to its essential and conserved function in the viral replication cycle. We have expressed, purified and developed assays for nsp5 protease activity. We screened the nsp5 protease against a custom chemical library of over 5,000 characterised pharmaceuticals. We identified calpain inhibitor I and three different peptidyl fluoromethylketones (FMK) as inhibitors of nsp5 activity in vitro, with IC50 values in the low micromolar range. By altering the sequence of our peptidomimetic FMK inhibitors to better mimic the substrate sequence of nsp5, we generated an inhibitor with a subnanomolar IC50. Calpain inhibitor I inhibited viral infection in monkey-derived Vero E6 cells, with an EC50 in the low micromolar range. The most potent and commercially available peptidyl-FMK compound inhibited viral growth in Vero E6 cells to some extent, while our custom peptidyl FMK inhibitor offered a marked antiviral improvement.

Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp12/7/8 RNA-dependent RNA Polymerase

The coronavirus disease 2019 (COVID-19) global pandemic has turned into the largest public health and economic crisis in recent history impacting virtually all sectors of society. There is a need for effective therapeutics to battle the ongoing pandemic. Repurposing existing drugs with known pharmacological safety profiles is a fast and cost-effective approach to identify novel treatments. The COVID-19 etiologic agent is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a single-stranded positive-sense RNA virus. Coronaviruses rely on the enzymatic activity of the replication-transcription complex (RTC) to multiply inside host cells. The RTC core catalytic component is the RNA-dependent RNA polymerase (RdRp) holoenzyme. The RdRp is one of the key druggable targets for CoVs due to its essential role in viral replication, high degree of sequence and structural conservation and the lack of homologs in human cells. Here, we have expressed, purified and biochemically characterised active SARS-CoV-2 RdRp complexes. We developed a novel fluorescence resonance energy transfer (FRET)-based strand displacement assay for monitoring SARS-CoV-2 RdRp activity suitable for a high-throughput format. As part of a larger research project to identify inhibitors for all the enzymatic activities encoded by SARS-CoV-2, we used this assay to screen a custom chemical library of over 5000 approved and investigational compounds for novel SARS-CoV-2 RdRp inhibitors. We identified 3 novel compounds (GSK-650394, C646 and BH3I-1) and confirmed suramin and suramin-like compounds as in vitro SARS-CoV-2 RdRp activity inhibitors. We also characterised the antiviral efficacy of these drugs in cell-based assays that we developed to monitor SARS-CoV-2 growth.

Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp13 Helicase

The coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global public health challenge. While the efficacy of vaccines against emerging and future virus variants remains unclear, there is a need for therapeutics. Repurposing existing drugs represents a promising and potentially rapid opportunity to find novel antivirals against SARS-CoV-2. The virus encodes at least nine enzymatic activities that are potential drug targets. Here we have expressed, purified and developed enzymatic assays for SARS-CoV-2 nsp13 helicase, a viral replication protein that is essential for the coronavirus life cycle. We screened a custom chemical library of over 5000 previously characterised pharmaceuticals for nsp13 inhibitors using a FRET-based high-throughput screening (HTS) approach. From this, we have identified FPA-124 and several suramin-related compounds as novel inhibitors of nsp13 helicase activity in vitro. We describe the efficacy of these drugs using assays we developed to monitor SARS-CoV-2 growth in Vero E6 cells.

Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp3 Papain-like Protease

The COVID-19 pandemic has emerged as the biggest life-threatening disease of this century. Whilst vaccination should provide a long-term solution, this is pitted against the constant threat of mutations in the virus rendering the current vaccines less effective. Consequently, small molecule antiviral agents would be extremely useful to complement the vaccination program. The causative agent of COVID-19 is a novel coronavirus, SARS-CoV-2, which encodes at least nine enzymatic activities that all have drug targeting potential. The papain-like protease (PLpro) contained in the nsp3 protein generates viral non-structural proteins from a polyprotein precursor, and cleaves ubiquitin and ISG protein conjugates. Here we describe the expression and purification of PLpro. We developed a protease assay that was used to screen a custom chemical library from which we identified Dihydrotanshinone I and Ro 08-2750 as compounds that inhibit PLpro in protease and isopeptidase assays and also inhibit viral replication in cell culture-based assays.

Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp15 Endoribonuclease

SARS-CoV-2 is responsible for COVID-19, a human disease that has caused over 2 million deaths, stretched health systems to near-breaking point and endangered the economies of countries and families around the world. Antiviral treatments to combat COVID-19 are currently lacking. Remdesivir, the only antiviral drug approved for the treatment of COVID-19, can affect disease severity, but better treatments are needed. SARS-CoV-2 encodes 16 non-structural proteins (nsp) that possess different enzymatic activities with important roles in viral genome replication, transcription and host immune evasion. One key aspect of host immune evasion is performed by the uridine-directed endoribonuclease activity of nsp15. Here we describe the expression and purification of nsp15 recombinant protein. We have developed biochemical assays to follow its activity, and we have found evidence for allosteric behaviour. We screened a custom chemical library of over 5000 compounds to identify nsp15 endoribonuclease inhibitors, and we identified and validated NSC95397 as an inhibitor of nsp15 endoribonuclease in vitro. Although NSC95397 did not inhibit SARS-CoV-2 growth in VERO E6 cells, further studies will be required to determine the effect of nsp15 inhibition on host immune evasion.