GLUT and HK: Two primary and essential key players in tumor glycolysis.

Cancer cells reprogram their metabolism to become "glycolysis-dominant," which enables them to meet their energy and macromolecule needs and enhancing their rate of survival. This glycolytic-dominancy is known as the "Warburg effect", a significant factor in the growth and invasion of malignant tumors. Many studies confirmed that members of the GLUT family, specifically HK-II from the HK family play a pivotal role in the Warburg effect, and are closely associated with glucose transportation followed by glucose metabolism in cancer cells. Overexpression of GLUTs and HK-II correlates with aggressive tumor behaviour and tumor microenvironment making them attractive therapeutic targets. Several studies have proven that the regulation of GLUTs and HK-II expression improves the treatment outcome for various tumors. Therefore, small molecule inhibitors targeting GLUT and HK-II show promise in sensitizing cancer cells to treatment, either alone or in combination with existing therapies including chemotherapy, radiotherapy, immunotherapy, and photodynamic therapy. Despite existing therapies, viable methods to target the glycolysis of cancer cells are currently lacking to increase the effectiveness of cancer treatment. This review explores the current understanding of GLUT and HK-II in cancer metabolism, recent inhibitor developments, and strategies for future drug development, offering insights into improving cancer treatment efficacy.

Targeting Fks1 proteins for novel antifungal drug discovery.

Fungal infections are a major threat to human health. The limited availability of antifungal drugs, the emergence of drug resistance, and a growing susceptible population highlight the critical need for novel antifungal agents. The enzymes involved in fungal cell wall synthesis offer potential targets for antifungal drug development. Recent studies have enhanced our focus on the enzyme Fks1, which synthesizes ß-1,3-glucan, a critical component of the cell wall. These studies provide a deeper understanding of Fks1's function in cell wall biosynthesis, pathogenicity, structural biology, evolutionary conservation across fungi, and interaction with current antifungal drugs. Here, we discuss the role of Fks1 in the survival and adaptation of fungi, guided by insights from evolutionary and structural analyses. Furthermore, we delve into the dynamics of Fks1 modulation with novel antifungal strategies and assess its potential as an antifungal drug target.

Taking cues from machine learning, compartmental and time series models for SARS-CoV-2 omicron infection in Indian provinces.

SARS-CoV-2, the virus responsible for COVID-19, posed a significant threat to the world. We analyzed COVID-19 dissemination data in the top ten Indian provinces by infection incidences using the Susceptible-Infectious-Removed (SIR) model, an Autoregressive Integrated Moving Average (ARIMA) time series model, a machine learning model based on the Random Forest, and distribution fitting. Outbreaks are expected to continue if the Basic Reproduction Number (R0) > 1, and infection waves are anticipated to end if the R0 < 1, as determined by the SIR model. Different parametric probability distributions are also fitted. Data collected from December 12, 2021, to March 31, 2022, encompassing data from both before and during the implementation of strict control measures. Based on the estimates of the model parameters, health agencies and government policymakers can develop strategies to combat the spread of the disease in the future, and the most effective technique can be recommended for real-world application for other outbreaks of COVID-19. The best method out of these could be also implemented further on the epidemiological data of other similar infectious agents.

A bis-quinoline ruthenium(II) arene complex with submicromolar cytotoxicity in castration-resistant prostate cancer cells.

A new Ru(II) arene chlorido organometallic complex [(η6-p-cymene)(L)RuCl]PF6 (named as pCYRuL) using 2-bis(quinolin-2-ylmethylene) hydrazine (L) was developed that exhibits potent anticancer activity against castration-resistant prostate cancer (CRPC) (IC50 = 0.71 µM), and it is 45 times more effective than the standard drug cisplatin (IC50 = 31.3 µM) in a castration-resistant human prostatic adenocarcinoma cell line (PC-3) but non-toxic in normal human kidney cells (HK2) as well as normal breast cells (MCF10A) and found that pCYRuL exerted anticancer activity via apoptosis induction and cell cycle arrest in the G2/M phase of PC-3 cells.

Deciphering drug discovery and microbial pathogenesis research in tuberculosis during the two decades of postgenomic era using entity mining approach.

We examined literature on Mycobacterium tuberculosis (Mtb) subsequent to its genome release, spanning years 1999-2020. We employed scientometric mapping, entity mining, visualization techniques, and PubMed and PubTator databases. Most popular keywords, most active research groups, and growth in quantity of publications were determined. By gathering annotations from the PubTator, we determined direction of research in the areas of drug hypersensitivity, drug resistance (AMR), and drug-related side effects. Additionally, we examined the patterns in research on Mtb metabolism and various forms of tuberculosis, including skin, brain, pulmonary, extrapulmonary, and latent tuberculosis. We discovered that 2011 had the highest annual growth rate of publications, at 19.94%. The USA leads the world in publications with 18,038, followed by China with 14,441, and India with 12,158 publications. Studies on isoniazid and rifampicin resistance showed an enormous increase. Non-tuberculous mycobacteria also been the subject of more research in effort to better understand Mtb physiology and as model organisms. Researchers also looked at co-infections like leprosy, hepatitis, plasmodium, HIV, and other opportunistic infections. Host perspectives like immune response, hypoxia, and reactive oxygen species, as well as comorbidities like arthritis, cancer, diabetes, and kidney disease etc. were also looked at. Symptomatic aspects like fever, coughing, and weight loss were also investigated. Vitamin D has gained popularity as a supplement during illness recovery, however, the interest of researchers declined off late. We delineated dominant researchers, journals, institutions, and leading nations globally, which is crucial for aligning ongoing and evolving landscape of TB research efforts. Recognising the dominant patterns offers important information about the areas of focus for current research, allowing biomedical scientists, clinicians, and organizations to strategically coordinate their efforts with the changing priorities in the field of tuberculosis research.

Echocardiography for Volume Assessment in Acute Myocardial Infarction.

Background Errors caused by improper volume estimation increase acute mortality rates in acute myocardial infarction (AMI). We aimed to determine volume status in AMI patients using echocardiography and to correlate the findings with clinical outcomes. Methods This cross-sectional, single-center study was performed at a tertiary care center in India between August 2017 and September 2020 involving AMI patients. We performed echocardiography for all patients. Parameters such as left ventricle (LV) and atrium size, LV end-diastolic pressure, inferior vena cava (IVC) size and size variation, velocity stroke volume, and velocity time integral variation were measured. B-lines were recorded by scanning 32 regions on the anterior chest in the supine position using cardiac probes of echocardiography. Results A total of 184 patients were enrolled in the study with male predominance (82.1%). The mean age of patients was 58.2 ± 10.7 years. Dilated (>2.1 cm) and collapsible (<50%) IVC, and B-lines were significantly associated with heart failure (HF) (p<0.001; r=0.87 and p<0.001; r=0.74, respectively). The area under receiver operating characteristics (AUROC) curve to diagnose HF at a cut-off value of >10 for B-lines was 0.897 (0.842-0.951). AUROC curve for IVC size in diagnosing hypovolemia was 0.063 (0.000-0.130). Conclusions Volume status based on IVC size and B-lines detected by echocardiography has a strong prognostic value in AMI patients and should be included in the routine assessment of these patients.

Comparison Between Distal Trans-radial Access and Conventional Trans-radial Access for Coronary Angiography.

Background Compared with a conventional wrist puncture for radial artery catheterization, a distal radial artery puncture has the advantage of reducing the incidence of radial artery occlusion (RAO). Aim The present study was designed to evaluate the feasibility of distal trans-radial access compared with conventional trans-radial access for coronary angiography. Methods A prospective, randomized, single-blinded, comparative study was conducted at a tertiary care center in India between December 2018 and November 2020. A total of 420 patients (aged >18 years) with signs and symptoms suggestive of coronary artery disease (CAD) and with a palpable radial artery in anatomical snuffbox were randomized into two groups. Group A comprised patients accessed at the distal trans-radial site, and Group B consisted of patients accessed at the conventional trans-radial site for coronary angiography. Baseline demographics, clinical history, and risk factors for CAD were documented. Procedural-related parameters and complications were compared between the two groups. Results The procedural success rate was non-significant between Group A and Group B (96% vs. 98%; p=0.38). Puncture in a single attempt was higher in Group B compared to Group A (92% vs. 78%; p<0.001). There was no significant difference between Group A and Group B for operation time (p=0.207), fluoroscopy time (p=0.183), and contrast volume (p=0.345). The rate of RAO was higher in Group B compared to Group A (13% vs. 2%; p<0.001). Radial artery hematoma/swelling at the puncture site between Group A (10%) and Group B (8%) was not significant (p=0.61). Post-procedural hemostasis time in Group A was 28 ± 7.86 minutes, and in Group B was 24 ± 6.23 minutes. Both post-procedural persistence of pain (p<0.001) and hand clumsiness (p<0.001) were significantly higher in Group B compared to Group A. Conclusion For coronary angiography, the distal trans-radial access site is a reliable and secure alternate access site.

In silico resources help combat cancer drug resistance mediated by target mutations.

Drug resistance causes catastrophic cancer treatment failures. Mutations in target proteins with altered drug binding indicate a main mechanism of cancer drug resistance (CDR). Global research has generated considerable CDR-related data and well-established knowledge bases and predictive tools. Unfortunately, these resources are fragmented and underutilized. Here, we examine computational resources for exploring CDR caused by target mutations, analyzing these tools based on their functional characteristics, data capacity, data sources, methodologies and performance. We also discuss their disadvantages and provide examples of how potential inhibitors of CDR have been discovered using these resources. This toolkit is designed to help specialists explore resistance occurrence effectively and to explain resistance prediction to non-specialists easily.

Design and Synthesis of Thiazole Scaffold-Based Small Molecules as Anticancer Agents Targeting the Human Lactate Dehydrogenase A Enzyme.

A new series of thiazole central scaffold-based small molecules of hLDHA inhibitors were designed using an in silico approach. Molecular docking analysis of designed molecules with hLDHA (PDB ID: 1I10) demonstrates that Ala 29, Val 30, Arg 98, Gln 99, Gly 96, and Thr 94 possessed strong interaction with the compounds. Compounds 8a, 8b, and 8d showed good binding affinity (-8.1 to -8.8 kcal/mol), whereas an additional interaction of NO2 at the ortho position in compounds 8c with Gln 99 through hydrogen bonding enhanced the affinity to -9.8 kcal/mol. Selected high-scored compounds were synthesized and screened for hLDHA inhibitory activities and in vitro anticancer activity in six cancer cell lines. Biochemical enzyme inhibition assays showed the highest hLDHA inhibitory activity observed with compounds 8b, 8c, and 8l. Compounds 8b, 8c, 8j, 8l, and 8m depicted significant anticancer activities, exhibiting IC50 values in the range of 1.65-8.60 µM in HeLa and SiHa cervical cancer cell lines. Compounds 8j and 8m exhibited notable anticancer activity with IC50 values of 7.90 and 5.15 µM, respectively, in liver cancer cells (HepG2). Interestingly, compounds 8j and 8m did not induce noticeable toxicity in the human embryonic kidney cells (HEK293). Insilico absorption, distribution, metabolism, and excretion profiling demonstrates that the compounds possess drug-likeness, and results may pave the way for the development of novel thiazole-based biologically active small molecules for therapeutics.

The metabolic crosstalk between PIN1 and the tumour microenvironment.

Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) is a member of a family of peptidyl-prolyl isomerases that specifically recognizes and binds phosphoproteins, catalyzing the rapid cis-trans isomerization of phosphorylated serine/threonine-proline motifs, which leads to changes in the structures and activities of the targeted proteins. Through this complex mechanism, PIN1 regulates many hallmarks of cancer including cell autonomous metabolism and the crosstalk with the cellular microenvironment. Many studies showed that PIN1 is largely overexpressed in cancer turning on a set of oncogenes and abrogating the function of tumor suppressor genes. Among these targets, recent evidence demonstrated that PIN1 is involved in lipid and glucose metabolism and accordingly, in the Warburg effect, a characteristic of tumor cells. As an orchestra master, PIN1 finely tunes the signaling pathways allowing cancer cells to adapt and take advantage from a poorly organized tumor microenvironment. In this review, we highlight the trilogy among PIN1, the tumor microenvironment and the metabolic program rewiring.

The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia.

Targeting critical epigenetic regulators reverses aberrant transcription in cancer, thereby restoring normal tissue function1-3. The interaction of menin with lysine methyltransferase 2A (KMT2A), an epigenetic regulator, is a dependence in acute leukaemia caused by either rearrangement of KMT2A or mutation of the nucleophosmin 1 gene (NPM1)4-6. KMT2A rearrangements occur in up to 10% of acute leukaemias and have an adverse prognosis, whereas NPM1 mutations occur in up to 30%, forming the most common genetic alteration in acute myeloid leukaemia7,8. Here, we describe the results of the first-in-human phase 1 clinical trial investigating revumenib (SNDX-5613), a potent and selective oral inhibitor of the menin-KMT2A interaction, in patients with relapsed or refractory acute leukaemia (ClinicalTrials.gov, NCT04065399). We show that therapy with revumenib was associated with a low frequency of grade 3 or higher treatment-related adverse events and a 30% rate of complete remission or complete remission with partial haematologic recovery (CR/CRh) in the efficacy analysis population. Asymptomatic prolongation of the QT interval on electrocardiography was identified as the only dose-limiting toxicity. Remissions occurred in leukaemias refractory to multiple previous lines of therapy. We demonstrate clearance of residual disease using sensitive clinical assays and identify hallmarks of differentiation into normal haematopoietic cells, including differentiation syndrome. These data establish menin inhibition as a therapeutic strategy for susceptible acute leukaemia subtypes.

A comprehensive review on the metal-based green valorized nanocomposite for the remediation of emerging colored organic waste.

In today's era, "green" synthesis is an emerging research trend. It has gained widespread attention owing to its dynamic behavior, reliability, simplicity, sustainability, and environment friendly approach for fabricating various nanomaterials. Green fabrication of metal/metal oxides nanomaterials, hybrid materials, and other metal-based nanocomposite can be utilized to remove toxic colored aqueous pollutants. Nanomaterials synthesized by using green approach is considered to be the significant tool to minimize unwanted or harmful by-products otherwise released from traditional synthesis methods. Various kinds of biosynthesized nanomaterials, such as animal waste and plant-based, have been successfully applied and well documented in the literature. However, their application part, especially for the cure of colored organic polluted water, has not been reported as a single review article. Therefore, the current work aims to assemble reports on using novel biosynthesized green metal-based nanomaterials to exclude harmful dyes from polluted water.

Targeting monocarboxylate transporters (MCTs) in cancer: How close are we to the clinics?

As a result of metabolic reprogramming, cancer cells display high rates of glycolysis, causing an excess production of lactate along with an increase in extracellular acidity. Proton-linked monocarboxylate transporters (MCTs) are crucial in the maintenance of this metabolic phenotype, by mediating the proton-coupled lactate flux across cell membranes, also contributing to cancer cell pH regulation. Among the proteins codified by the SLC16 gene family, MCT1 and MCT4 isoforms are the most explored in cancers, being overexpressed in many cancer types, from solid tumours to haematological malignancies. Similarly to what occurs in particular physiological settings, MCT1 and MCT4 are able to mediate lactate shuttles among cancer cells, and also between cancer and stromal cells in the tumour microenvironment. This form of metabolic cooperation is responsible for important cancer aggressiveness features, such as cell proliferation, survival, angiogenesis, migration, invasion, metastasis, immune tolerance and therapy resistance. The growing understanding of MCT functions and regulation is offering a new path to the design of novel inhibitors that can be foreseen in clinical practices. This review provides an overview of the role of MCT isoforms in cancer and summarizes the recent advances in their pharmacological targeting, highlighting the potential of new potent and selective MCT1 and/or MCT4 inhibitors in cancer therapeutics, and anticipating its inclusion in clinical practice.

G-quadruplex-mediated specific recognition, stabilization and transcriptional repression of bcl-2 by small molecule.

The presence of the G-quadruplex (G4) structure in the promoter region of the human bcl-2 oncogenes makes it a promising target for developing anti-cancer therapeutics. Bcl-2 inhibits apoptosis, and its frequent overexpression in cancer cells contributes to tumor initiation, progression, and resistance to therapy. Small molecules that can specifically bind to bcl-2 G4 with high affinity and selectivity are remaining elusive. Here, we report that small molecule 1,3-bis-) furane-2yl-methylidene-amino) guanidine (BiGh) binds to bcl-2 G4 DNA structure with very high affinity and selectivity over other genomic G4 DNA structures and duplex DNA. BiGh stabilizes folded parallel conformation of bcl-2 G4 via non-covalent and electrostatic interactions and increases the thermal stabilization up to 15 °C. The ligand significantly suppresses the bcl-2 transcription in HeLa cells by a G4-dependent mechanism and induces cell cycle arrest which promotes apoptosis. The in silico ADME profiling confirms the potential 'drug-likeness' of BiGh. Our results showed that BiGh stabilizes the bcl-2 G-quadruplex motif, downregulates the bcl-2 gene transcription as well as translation process in cervical cancer cells, and exhibits potential anti-cancer activity. This work provides a potential platform for the development of lead compound(s) as G4 stabilizers with drug-like properties of BiGh for cancer therapeutics.

Discovery of a potent Guanidine derivative that selectively binds and stabilizes the human BCL-2 G-quadruplex DNA and downregulates the transcription.

G-quadruplex also known as G4 (GQ) structures, are a non-canonical kind of DNA or RNA secondary structure that may develop inside guanine-rich nucleic acid sequences. They may be found in a variety of locations in the human genome, such as gene promoters, 5' untranslated region, and telomeres, among others. Because of their significance in biology, G4 structures are recognized as promising pharmacological targets, particularly for therapeutics against cancer. This has led to the discovery of small molecules that can stabilize G4 structures. Small molecules that interact with quadruplexes offer a wide range of potential applications, including not just as medications but also as sensors for quadruplexes structures. The BCL-2 is a proto-oncogene that often gets mutated in lethal cancer and could be an interesting target for developing an anti-cancer drug. In the present study, we have employed various biophysical techniques such as fluorescence, CD, Isothermal calorimetry, gel retardation, and PCR stop assay, indicating that Guanidine derivatives GD-1 and GD-2 selectively interact with high affinity with BCL-2 GQ over other G-quadruplex DNA and duplex DNA. The most promising small molecule GD-1 increases the thermostability of the BCL-2 GQ structure by 12°C. Our biological experiments such as ROS generation, qRT-PCR, western blot, TFP based reporter assay, show that the GD-1 ligand causes a synthetic lethal interaction by suppressing the expression of BCL-2 genes via interaction and stabilization of its promoter GQ strucure in HeLa cells and act as a potential anti-cancer agent.

Axatilimab for Chronic Graft-Versus-Host Disease After Failure of at Least Two Prior Systemic Therapies: Results of a Phase I/II Study.

PURPOSE: Chronic graft-versus-host disease (cGVHD) remains the major cause of late morbidity after allogeneic hematopoietic cell transplantation. Colony-stimulating factor 1 receptor (CSF-1R)-dependent macrophages promote cGVHD fibrosis, and their elimination in preclinical studies ameliorated cGVHD. Axatilimab is a humanized monoclonal antibody that inhibits CSF-1R signaling and restrains macrophage development. PATIENTS AND METHODS: This phase I (phI)/phase II (phII) open-label study (ClinicalTrials.gov identifier: NCT03604692) evaluated safety, tolerability, and efficacy of axatilimab in patients age ≥ 6 years with active cGVHD after ≥ 2 prior systemic therapy lines. Primary objectives in phI were to identify the optimal biologic and recommended phII dose and in phII to evaluate the overall (complete and partial) response rate (ORR) at the start of treatment cycle 7. RESULTS: Forty enrolled patients (17 phI; 23 phII) received at least one axatilimab dose. In phI, a dose of 3 mg/kg given once every 4 weeks met the optimal biologic dose definition. Two dose-limiting toxicities occurred at the 3 mg/kg dose given once every 2 weeks. At least one treatment-related adverse event (TRAE) was observed in 30 patients with grade ≥ 3 TRAEs in eight patients, the majority known on-target effects of CSF-1R inhibition. No cytomegalovirus reactivations occurred. With the 50% ORR at cycle 7 day 1, the phII cohort met the primary efficacy end point. Furthermore, the ORR in the first six cycles, an end point supporting regulatory approvals, was 82%. Responses were seen in all affected organs regardless of prior therapy. Fifty-eight percent of patients reported significant improvement in cGVHD-related symptoms using the Lee Symptom Scale. On-target activity of axatilimab was suggested by the decrease in skin CSF-1R-expressing macrophages. CONCLUSION: Targeting profibrotic macrophages with axatilimab is a therapeutically promising novel strategy with a favorable safety profile for refractory cGVHD.

Targeting Virus-Induced Reprogrammed Cell Metabolism via Glycolytic Inhibitors: An Effective Therapeutic Approach Against SARS-CoV-2.

Reprogrammed cell metabolism has been observed in a wide range of virally infected cells. Viruses do not have their metabolism; they rely on the cellular metabolism of the host to ensure the energy and macromolecules requirement for replication. Like other viruses, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) does not own its metabolism, but virus infected cells adopt aberrant cell metabolism. Infected viral use the energy and macromolecules to make their own copies; to do so, they need to increase the rate of metabolism to ensure the requirement of macromolecules. In contrast, the cellular metabolism of noninfected cells is more plastic than infected cells. Therefore, it is essential to examine the virus infection in the context of metabolic alterations of host cells. A novel therapeutic approach is urgently required to treat highly infectious COVID-19 disease and its pathogenesis. Interference of glucose metabolism might be a promising strategy to determine COVID-19 treatment options. Based on the recent research, this mini-review aims to understand the impact of reprogrammed cell metabolism in COVID-19 pathogenesis and explores the potential of targeting metabolic pathways with small molecules as a new strategy for the development of a novel drug to treat COVID-19 disease. This type of research line provides new hope in the development of antiviral drugs by targeting hijacked cell metabolism in case of viral diseases and also in COVID-19.

Current understanding of biological interactions and processing of DNA origami nanostructures: Role of machine learning and implications in drug delivery.

DNA origami has emerged as an exciting avenue that provides a versatile two and three-dimensional DNA-based platform for nanomedicine and drug delivery applications. Their incredible programmability, custom synthesis, efficiency, biocompatibility, and physio-chemical nature make DNA origami ideal for biomedical applications. Several recent studies demonstrated the potential of DNA origami for different technological applications, especially in drug delivery. However, several challenges related to their intracellular stability, elicitation of the immune response, and cellular fate limit the in-vivo application of these nanostructures. In this review, we critically assess the molecular-level interactions of DNA nanostructures with biological systems that will be helpful to engineer and optimize DNA nanostructures for bio applications. We highlight the hurdles that impair the potential applicability of DNA origami nanostructures in the biology and medicine field. We have also expanded the details of key strategies to overcome the limitations and extend the boundaries of DNA origami closer to nanomedicine. Finally, we explore the role Artificial Intelligence and Machine Learning techniques can play to accelerate the process of their clinical applications.

Ensemble multimodal deep learning for early diagnosis and accurate classification of COVID-19.

Over the past few years, the awful COVID-19 pandemic effect has become a lethal sickness. The processing of the gathered samples requires extra time due to the use of medical diagnostic equipment, methodologies, and clinical testing procedures for the early diagnosis of infected individuals. An innovative multimodal paradigm for the early diagnosis and precise categorization of COVID-19 is put up as a solution to this issue. To extract distinguishing features from the prepared chest X-ray picture and cough (audio) database, chest X-ray-based and cough-based model are used here. Other public chest X-ray image datasets, and the Coswara cough (audio) dataset containing 92 COVID-19 positive, and 1079 healthy subjects (people) using the deep Uniform-Net, and Convolutional Neural Network (CNN). The weighted sum-rule fusion method and ensemble deep learning algorithms are utilized to further combine the extracted features. For the early diagnosis of patients, the framework offers an accuracy of 98.67%.

Modeling Global COVID-19 Dissemination Data After the Emergence of Omicron Variant Using Multipronged Approaches.

The COVID-19 pandemic has followed a wave pattern, with an increase in new cases followed by a drop. Several factors influence this pattern, including vaccination efficacy over time, human behavior, infection management measures used, emergence of novel variants of SARS-CoV-2, and the size of the vulnerable population, among others. In this study, we used three statistical approaches to analyze COVID-19 dissemination data collected from 15 November 2021 to 09 January 2022 for the prediction of further spread and to determine the behavior of the pandemic in the top 12 countries by infection incidence at that time, namely Distribution Fitting, Time Series Modeling, and Epidemiological Modeling. We fitted various theoretical distributions to data sets from different countries, yielding the best-fit distribution for the most accurate interpretation and prediction of the disease spread. Several time series models were fitted to the data of the studied countries using the expert modeler to obtain the best fitting models. Finally, we estimated the infection rates (ß), recovery rates (γ), and Basic Reproduction Numbers ([Formula: see text]) for the countries using the compartmental model SIR (Susceptible-Infectious-Recovered). Following more research on this, our findings may be validated and interpreted. Therefore, the most refined information may be used to develop the best policies for breaking the disease's chain of transmission by implementing suppressive measures such as vaccination, which will also aid in the prevention of future waves of infection.