The recent outbreak of SARS-CoV-2 significantly increased the need to find inhibitors that target the essential enzymes for virus replication in the host cells. This systematic review was conducted to identify potential inhibitors of SARS-CoV, MERS-CoV, and SARS-CoV-2 helicases that have been tested by in vitro methods. The inhibition mechanisms of these compounds were discussed in this review, in addition to their cytotoxic and viral infection protection properties. The databases PUBMED/MEDLINE, EMBASE, SCOPUS, and Web of Science were searched using different combinations of the keywords “helicase”, “nsp13”, “inhibitors”, “coronaviridae”, “coronaviruses”, “virus replication”, “replication”, and “antagonists and inhibitors". By the end of this search, a total of 6854 articles had been identified. Thirty-one articles were included in this review. These studies reported the inhibitory effects of 309 compounds on SARS-CoV, MERS-CoV, and SARS-CoV-2 helicase activities measured by in vitro methods. Helicase inhibitors were categorized according to the type of coronavirus and the type of tested enzymatic activity, nature, approval, inhibition level, cytotoxicity, and viral infection protection effects. These inhibitors are classified according to the site of their interaction with the coronavirus helicases into four types: zinc-binding site inhibitors, nucleic acid binding site inhibitors, nucleotide-binding site inhibitors, and inhibitors with no clear interaction site. Evidence from in vitro studies suggests that helicase inhibitors have a high potential as antiviral agents. Several helicase inhibitors tested in vitro showed good antiviral activities while maintaining moderate cytotoxicity. These inhibitors should be clinically investigated to determine their efficiency in treating different coronavirus infections, particularly COVID-19.

Background: Biochemistry is a cornerstone of medical education. Its knowledge is integral to the understanding of complex biological processes and how they are applied in several areas in health care. Also, its significance is reflected in the way it informs the practice of medicine, which can guide and help in both diagnosis and treatment. However, the retention of biochemistry knowledge over time remains a dilemma. Long-term retention of such crucial information is extremely important, as it forms the foundation upon which clinical skills are developed and refined. The effectiveness of biochemistry education, and consequently its long-term retention, is influenced by several factors. Educational methods play a critical role; interactional and integrative teaching approaches have been suggested to enhance retention compared with traditional didactic methods. The frequency and context in which biochemistry knowledge is applied in clinical settings can significantly impact its retention. Practical application reinforces theoretical understanding, making the knowledge more accessible in the long term. Prior knowledge (familiarity) of information suggests that it is stored in long-term memory, which makes its retention in the long term easier to recall. Objectives: This investigation was conducted at King Saud bin Abdulaziz University for Health Sciences in Riyadh, Saudi Arabia. The aim of the study is to understand the dynamics of long-term retention of biochemistry among medical students. Specifically, it looks for the association between students’ familiarity with biochemistry content and actual knowledge retention levels. Methods: A cross-sectional correlational survey involving 240 students from King Saud bin Abdulaziz University for Health Sciences was conducted. Participants were recruited via nonprobability convenience sampling. A validated biochemistry assessment tool with 20 questions was used to gauge students’ retention in biomolecules, catalysis, bioenergetics, and metabolism. To assess students’ familiarity with the knowledge content of test questions, each question is accompanied by options that indicate students’ prior knowledge of the content of the question. Statistical analyses tests such as Mann-Whitney U test, Kruskal-Wallis test, and chi-square tests were used. Results: Our findings revealed a significant correlation between students’ familiarity of the content with their knowledge retention in the biomolecules (r=0.491; P<.001), catalysis (r=0.500; P<.001), bioenergetics (r=0.528; P<.001), and metabolism (r=0.564; P<.001) biochemistry knowledge domains. Conclusions: This study highlights the significance of familiarity (prior knowledge) in evaluating the retention of biochemistry knowledge. Although limited in terms of generalizability and inherent biases, the research highlights the crucial significance of student’s familiarity in actual knowledge retention of several biochemistry domains. These results might be used by educators to customize instructional methods in order to improve students’ long-term retention of biochemistry information and boost their clinical performance.

To assess the efficacy of Zafirlukast as a SARS-CoV-2 Helicase Inhibitor in adult patients with moderate COVID-19 symptoms (hospitalized patients with COVID-19 pneumonia who were not admitted to an intensive care unit). We conducted a randomized, double blind, placebo-controlled, pilot trial with adult patients with moderate COVID-19 pneumonia. The sample was randomized to Zafirlukast 10 mg BD for 10 days plus standard care vs placebo plus standard care. The primary outcome was the complete resolution of all symptoms. The secondary outcomes were the duration of oxygen therapy, and length of hospital stay (LOS). In total, 40 patients were randomized (20 to Zafirlukast and 20 to the control). The time to the resolution of clinical symptoms in both groups was not significantly different. Regarding the fever, 0.3 days [95 % CI, − 1.19, 0.69], p = 0.76, for shortness of breath, the difference was 0.4 days [95 % CI, − 2.67, 3.46], p = 0.68, for cough the difference was 0.2 days [95 % CI, − 1.45, 1.95], p = 0.98, for sputum the difference was 0.5 days [95 % CI, − 0.75, 1.85], p = 0.09, for vomiting the difference was 0.1 days [95 % CI, − 0.50, 0.30], p = 0.93, for fatigue the difference was 0.3 days [95 % CI, − 4.32, 3.62], p = 0.64. The LOS per day for the two groups was not significantly different, 1.1 days [95 % CI,− 2.03, 4.28], p = 0.94, nor was the duration of oxygen therapy per days, 1.3 days [95 % CI, − 1.79, 4.49], p = 0.49. Regarding the 7 category ordinary scale, there was no significant difference between the two groups at day 7 (p-value = 0.62), day 14 (p-value = 0.60) and day 28 (p-value = 0.48). Among adult patients hospitalized with COVID-19 pneumonia, the treatment with Zafirlukast, compared to placebo, did not significantly improve symptoms resolution.

During infection, the coronavirus nonstructural protein 15 (Nsp15), a uridine-specific endoribonuclease, suppresses the host cell's antiviral response. Recently, researchers have paid more attention to this relatively underexplored yet potentially viable drug target. In this study, we employed FRET-based screening assays to identify potent Nsp15 inhibitors. Subsequently, we used active-site in silico docking methods to design new molecules with enhanced inhibitory properties. Solution assays were used to measure the potency and determine the mechanism of these inhibitors. We identified a novel class of thiazolidinedione and rhodanine analogs that inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Nsp15. Docking these compounds into the uridine-binding site shows that most analogs form two hydrogen bonds with Ser294. The most potent inhibitors are compounds 5-(3-quinolin-4-yl-allylidene)-thiazolidine-2,4-dione (KCO237) and 5-(3-isoquinolin-4-yl-allylidene)-2-thioxo-thiazolidin-4-one (KCO251) (IC₅₀: 0.304 μM and 0.931 μM, respectively). The inhibition kinetics of KCO237 and KCO251 best align with a reversible mixed inhibition model. Mutating Ser294 did not completely abolish Nsp15 activity or the inhibitory effect of KCO237 or KCO251. These findings suggest that thiazolidinedione and rhodanine analogs likely inhibit Nsp15 by binding to the uridine active site while also implicating a possible secondary allosteric-binding site. The ability of these compounds to inhibit VERO 6 cell infection with SARS-CoV-2 at subtoxic levels highlights their potential for development as novel antiviral treatments for SARS-CoV-2 and other coronavirus-related diseases.

Introduction: Increasing evidence shows that hyperglycemia-induced glucotoxicity and lipotoxicity that usually accompany diabetes development damage the endoplasmic reticulum and mitochondria of the hepatocytes in diabetic patients. Clinical studies highlighted the association between type 2 diabetes mellitus, comorbidities, and medications with liver function. The objective of this study is to explore the association between liver function tests’ abnormalities and comorbidities, medications, and other risk factors in type 2 diabetes patients registered in the Best-Care system of the Saudi Ministry of National Guard-Health Affairs.Methods: This is a cross-sectional study employing a chart of patients diagnosed with type 2 diabetes mellitus. We drew a simple random sample of 523 T2DM patients who had a liver function test from the Best-Care database of the Ministry. We applied various statistical analyses, including Student’s independent t-test, Pearson’s chi-squared test, Fisher’s exact test, and odd ratios, to measure associations between different variables and liver function tests’ abnormalities.Results: About 35% of patients included in this study showed an abnormal level of gamma-glutamyl transferase and prothrombin time. Abnormalities of serum albumin, prothrombin time, and total serum protein tests were significantly associated with age (P < 0.05). Gamma-glutamyl transferase test abnormalities were significantly associated with gender (P < 0.05). The study found associations between several comorbidities and the abnormalities of liver function tests. These tests include the total bilirubin, albumin, total serum protein, gamma-glutamyl trans, international normalized ratio, and alanine aminotransferase. The associations were at significant levels (P < 0.05). Liraglutide was significantly associated with aspartate aminotransferase (OR = 14.40, 95% CI = 2.8, 73.2), while allopurinol was significantly associated with international normalized ratios (OR = 24.67, 95% CI = 2.95, 206.58) and total serum protein (OR = 5.44, 95% CI = 1.43, 20.83).Discussion: This study is the first to examine the association between type 2 diabetes mellitus and liver function tests’ abnormalities in Saudi Arabia. Although the results have a limited generalizability due to inherent biases, the findings align with similar studies in other populations. The study stresses the need to monitor liver functions, especially of T2DM patients who suffer from other conditions.

Following the success of our first therapeutic discovery conference in 2017 and the selection of King Abdullah International Medical Research Centre (KAIMRC) as the first Phase 1 clinical site in the Kingdom of Saudi Arabia, we organized our second conference in partnership with leading institutions in academic drug discovery, which included the Structural Genomic Constorium (Oxford, UK), Fraunhofer (Germany) and Institute Material Medica (China); the participation of members of the American Drug Discovery Consterium; European Biotech companies; and local pharma companies, SIPMACO and SudairPharma. In addition, we had European and Northern American venture capital experts attending and presenting at the conference. The purpose of the conference was to bridge the gap between biotech, pharma and academia regarding drug discovery and development. Its aim primarily was to: (a) bring together world experts on academic drug discovery to discuss and propose new approaches to discover and develop new therapies; (b) establish a permanent platform for scientific exchange between academia and the biotech and pharmaceutical industries; (c) entice national and international investors to consider funding drugs discovered in academia; (d) educate the population about the causes of diseases, approaches to prevent them from happening and their cure; (e) attract talent to consider the drug discovery track for their studies and career. During the conference, we discussed the unique academic drug discovery disrupting business models, which can make their discoveries easily accessible in an open source mode. This unique model accelerates the dissemination of knowledge to all world scientists to guide them in their research. This model is aimed at bringing effective and affordable medicine to all mankind in a very short time. Moreover, the program discussed rare disease targets, orphan drug discovery, immunotherapy discovery and process, the role of bioinformatics in drug discovery, anti-infective drug discovery in the era of bad bugs, natural products as a source of novel drugs and innovative drug formulation and delivery. Additionally, as the conference was organized during the surge of the epidemic, we dedicated the first day (25 February) to coronavirus science, detection and therapy. The day was co-organized with the King Saud bin Abdulaziz University for Health Sciences, Kingdom of Saudi Arabia(KSA) Ministry of Education to announce the grant winner for infectious diseases. Simultaneously, intensive courses were delivered to junior scientists on the principle of drug discovery, immunology and clinical trials, as well as rare diseases. The second therapeutics discovery forum provided a platform for interactive knowledge sharing and the convergence of researchers, governments, pharmaceuticals, biopharmaceuticals, hospitals and non-profit organizations on the topic of academic drug discovery. The event presented showcases on global drug discovery initiatives and demonstrated how collaborations are leading to successful new therapies. In line with the KSA 2030 vision on becoming world leaders with an innovative economy and healthy population, therapeutic discovery is becoming an area of interest to science leaders in the kingdom, and our conference gave us the opportunity to identity key areas of interest as well as potential future collaborations.