Computational analysis of antiviral drugs using topological descriptors.

Many health challenges are attributed to viral infections, which represent significant concerns in public health. Among these infections, diseases such as herpes simplex virus (HSV), cytomegalovirus (CMV), and varicella-zoster virus (VZV) infections have garnered attention due to their prevalence and impact on human health. There are specific antiviral medications available for the treatment of these viral infections. Drugs like Cidofovir, Valacyclovir, and Acyclovir are commonly prescribed. These antiviral drugs are known for their efficacy against herpesviruses and related viral infections, leveraging their ability to inhibit viral DNA polymerase. A molecular descriptor is a numerical value that correlates with specific physicochemical properties of a molecular graph. This article explores the calculation of distance-based topological descriptors, including the Trinajstic, Mostar, Szeged, and PI descriptors for the aforementioned antiviral drugs. These descriptors provide insights into these drugs' structural and physicochemical characteristics, aiding in understanding their mechanism of action and the development of new therapeutic agents.

Topological Insights into Nanostar Dendrimers by Computing the Augmented Zagreb Index.

BACKGROUND: The field of nanobiotechnology uses precise nanofabrication techniques to advance our understanding and control of biological systems. Due to their remarkable properties, dendrimers, which are hyperbranched macromolecular structures with distinct and well-defined architectures, have emerged as pivotal entities within this field. They are gaining increasing attention for their potential to catalyze a paradigm shift in medical therapeutics, biotechnological applications, and advanced material sciences. OBJECTIVE: This paper focuses on a novel analytical expression and determines the precise value of the augmented Zagreb index, a topological descriptor, for eight classes of nanostar dendrimers. METHODS: The Zagreb index is a topological invariant to predict molecular behaviour and reactivity. In this paper, we have explored its application in characterizing the branching of nanostar dendrimers through computational modelling and mathematical rigor. RESULTS: Our research has measured the augmented Zagreb index for nanostar dendrimers, which fall into eight distinct classes. The results better explain the relationship between the dendrimers' topology and chemical properties. This correlation has implications for their structural stability and reactivity, potentially leading to new applications. CONCLUSION: Developing the augmented Zagreb index for nanostar dendrimers is a significant breakthrough in nanobiotechnology. Based on the correlation between the calculated topological index and the corresponding molecular attributes, our analytical approach has opened up new possibilities for designing and synthesizing dendrimers tailored to specific functions in medical and material science applications. This precise topological quantification could significantly enhance the utility and functionalization of dendrimers in cutting-edge nanotechnological applications.

Topological analysis of tetracyanobenzene metal-organic framework.

Metal-organic frameworks (MOFs) are vital in modern material science, offering unique properties for gas storage, catalysis, and drug delivery due to their highly porous and customizable structures. Chemical graph theory emerges as a critical tool, providing a mathematical model to represent the molecular structure of these frameworks. Topological indices/molecular descriptors are mathematical formulations applied to molecular models, enabling the analysis of physicochemical properties and circumventing costly lab experiments. These descriptors are crucial for quantitative structure-property and structure-activity relationship studies in mathematical chemistry. In this paper, we study the different molecular descriptors of tetracyanobenzene metal-organic framework. We also give numerical comparison of computed molecular descriptors.

Biochemical, Toxicological, and in Silico Aspects of Trillium govanianum Wall. ex D.Don (Trilliaceae): A Rich Source of Natural Bioactive Compounds.

Trillium govanianum is a high-value medicinal herb, having multifunctional traditional and culinary uses. The present investigation was carried out to evaluate the phytochemical, biological and toxicological parameters of the T. govanianum Wall. ex D. Don (Family: Trilliaceae) roots collected from Azad Kashmir, Pakistan. Phytochemical profiling was achieved by determining total bioactive contents (total phenolic and flavonoid contents) and UHPLC-MS analysis. For biological evaluation, antioxidant activities (DPPH, ABTS, FRAP, CUPRAC, phosphomolybdenum, and metal chelation assays) and enzyme inhibition activities (against AChE, BChE, glucosidase, amylase, and tyrosinase) were performed. Moreover, cytotoxicity was assessed against three human carcinoma cell lines (MDA-MB-231, CaSki, and DU-145). The tested extract was found to contain higher total phenolics (7.56 mg GAE/g dry extract) as compared to flavonoid contents (0.45 mg RE/g dry extract). Likewise, for the antioxidant activity, higher CUPRAC activity was noted with 39.84 mg TE/g dry extract values. In the case of enzyme assays, higher activity was pointed out against the cholinesterase, glucosidase and tyrosinase enzymes. The plant extract displayed significant cytotoxicity against the cell lines examined. Moreover, the in-silico studies highlighted the interaction between the important phytochemicals and tested enzymes. To conclude, the assessed biological activity and the existence of bioactive phytochemicals in the studied plant extract may pave the way for the development of novel pharmaceuticals.

Chest X-Ray Severity Index as a Predictor of Requiring Invasive Positive Pressure Ventilation in COVID-19 Positive Patients.

The aim of this study is to see the role of the chest X-ray severity index (Brixia score) as a predictor of requiring invasive positive pressure ventilation in COVID-19-positive patients. This descriptive cross-sectional prospective study were carried out in the Department of Pulmonology and Radiology, Mayo Hospital, Lahore. The data were collected from 1st May to 30th July 2020 from 60 consecutive COVID-19 positive patients. Analysis was conducted using each patient's age, gender, clinical presentation, and the report of CXR containing the most elevated score. The mean age of the study participants was 59.43±11.27, and 81.7% of patients had positive Brixia scores (≥8). Brixia score had high sensitivity (93.886) and specificity (90.91%) to predict the need for IPPV using chest X-rays. It showed excellent predictive power, having a high numerical AUC (0.870) and a statistically significant p-value (<0.0001). High Brixia score conferred a high risk of the need for invasive positive pressure ventilation due to COVID-19. Key Words: Chest X-ray, Brixia score, COVID-19, Invasive positive pressure ventilation.

Computing the partition dimension of certain families of Toeplitz graph.

Let G = (V(G), E(G)) be a graph with no loops, numerous edges, and only one component, which is made up of the vertex set V(G) and the edge set E(G). The distance d(u, v) between two vertices u, v that belong to the vertex set of H is the shortest path between them. A k-ordered partition of vertices is defined as ß = {ß1, ß2, …, ß k }. If all distances d(v, ß k ) are finite for all vertices v ∈ V, then the k-tuple (d(v, ß1), d(v, ß2), …, d(v, ß k )) represents vertex v in terms of ß, and is represented by r(v|ß). If every vertex has a different presentation, the k-partition ß is a resolving partition. The partition dimension of G, indicated by pd(G), is the minimal k for which there is a resolving k-partition of V(G). The partition dimension of Toeplitz graphs formed by two and three generators is constant, as shown in the following paper. The resolving set allows obtaining a unique representation for computer structures. In particular, they are used in pharmaceutical research for discovering patterns common to a variety of drugs. The above definitions are based on the hypothesis of chemical graph theory and it is a customary depiction of chemical compounds in form of graph structures, where the node and edge represent the atom and bond types, respectively.

Clinical efficacy of iodine complex in SARS-CoV-2-infected patients with mild to moderate symptoms: study protocol for a randomized controlled trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by the novel coronavirus-infected millions globally. Despite a wide range of advised options for the treatment of COVID-19, a single strategy to tackle this pandemic remains elusive, thus far. That is why we are conducting a clinical trial to find out the efficacy of iodine complex to clear a viral load of severe respiratory syndrome coronavirus-2 (SARS-CoV-2) along with a reduction in time taken to alleviate symptoms. METHOD: The proposed study is a placebo-controlled, add-on, randomized trial using parallel group designs. This is a closed-label and adaptive with sample size reassessment, multi-centered design with a 1:1:1:1 allocation ratio and superiority framework. It will be conducted in Shaikh Zayed Post-Graduate Medical Complex, Ali Clinic, and Doctors Lounge, Lahore, Pakistan. This study will have three arms of mild to moderately symptomatic COVID-19 patients (50 patients in each) which will receive ionic-iodine polymer complex with 200 mg of elemental iodine: interventional arm A will have encapsulated, arm B will receive suspension syrup form, arm C will get throat spray, while arm X will be standard care with placebo. Data will be collected on self-constructed, close-ended questionnaires after obtaining written consent. Data will be analyzed using SAS version 9.4. COVID-19 patients will be monitored by RT-PCR and HRCT (high-resolution computed tomography) chest. In addition to these, the duration of the symptomatic phase and mortality benefits will be analyzed in both groups. DISCUSSION: The study is designed to measure the superior efficacy of the iodine complex as an add-on in treating COVID-19-positive patients with mild to moderate symptoms. This combination is hypothesized to improve various parameters like rapid viral load reduction, clinical and radiological improvement, lower mortality, and reduction in hospitalization. The trial will aid in devising a better strategy to cope with COVID-19 in a relatively inexpensive and accessible way. The implications are global, and this could prove itself to be the most manageable intervention against COVID-19 especially for patients from limited-resource countries with deprived socioeconomic status. TRIAL REGISTRATION: ClinicalTrials.gov NCT04473261 . Registered on July 16, 2020.

Incessant threat of COVID-19 variants: Highlighting need for a mix of FDA-approved artificial intelligence tools and community pharmacy services.

Seamless integration of artificial intelligence (AI) technology, especially FDA-approved AI tools, in community pharmacies can build increasingly effective and easy care pathways, thereby minimizing burden on healthcare system, and ensuring compliance to preventive measure through limiting hospital visits. In this regard, the WHO needs to enlist and provide guidance on most promising AI tools that can be implemented in community pharmacy settings.

Bounds on the Partition Dimension of Convex Polytopes.

AIMS AND OBJECTIVE: The idea of partition and resolving sets play an important role in various areas of engineering, chemistry and computer science such as robot navigation, facility location, pharmaceutical chemistry, combinatorial optimization, networking, and mastermind game. METHODS: In a graph, to obtain the exact location of a required vertex, which is unique from all the vertices, several vertices are selected; this is called resolving set, and its generalization is called resolving partition, where selected vertices are in the form of subsets. A minimum number of partitions of the vertices into sets is called partition dimension. RESULTS: It was proved that determining the partition dimension of a graph is a nondeterministic polynomial time (NP) problem. In this article, we find the partition dimension of convex polytopes and provide their bounds. CONCLUSION: The major contribution of this article is that due to the complexity of computing the exact partition dimension, we provide the bounds and show that all the graphs discussed in the results have partition dimensions either less or equals to 4, but not greater than 4.

Total Irregularity Strengths of an Arbitrary Disjoint Union of (3,6)- Fullerenes.

AIMS AND OBJECTIVE: A fullerene graph is a mathematical model of a fullerene molecule. A fullerene molecule, or simply a fullerene, is a polyhedral molecule made entirely of carbon atoms other than graphite and diamond. Chemical graph theory is a combination of chemistry and graph theory, where theoretical graph concepts are used to study the physical properties of mathematically modeled chemical compounds. Graph labeling is a vital area of graph theory that has application not only within mathematics but also in computer science, coding theory, medicine, communication networking, chemistry, among other fields. For example, in chemistry, vertex labeling is being used in the constitution of valence isomers and transition labeling to study chemical reaction networks Method: In terms of graphs, vertices represent atoms while edges stand for bonds between the atoms. By tvs (tes) we mean the least positive integer for which a graph has a vertex (edge) irregular total labeling such that no two vertices (edges) have the same weights. A (3,6)-fullerene graph is a non-classical fullerene whose faces are triangles and hexagons Results: Here, we study the total vertex (edge) irregularity strength of an arbitrary disjoint union of (3,6)-fullerene graphs and provide their exact values. CONCLUSION: The lower bound for tvs (tes) depends on the number of vertices. Minimum and maximum degree of a graph exist in literature, while to get different weights, one can use sufficiently large numbers, but it is of no interest. Here, by proving that the lower bound is the upper bound, we close the case for (3,6)-fullerene graphs.

Polynomials of Degree-Based Indices of Metal-Organic Networks.

AIM AND OBJECTIVE: Metal-organic network (MON) is a special class of molecular compounds comprising groups of metal ions and carbon-based ligand. These chemical compounds are examined employing one, two- or three-dimensional formation of porous ore and subfamilies of polymers. Metal-organic networks are frequently utilized in catalysis for the parting & distilling of different gases and by means of conducting solid or super-capacitor. In various scenarios, the compounds are observed to maintain a balance in the procedure of deletion or diluter of the molecule and can be rebuilt with another molecular compound. The physical solidity and mechanical characteristics of the metal-organic network have attained great attention due to the above-mentioned properties. This study was undertaken to find the polynomials of MON. METHODS: Topological descriptor is a numerical number that is utilized to predict the natural correlation amongst the Physico-chemical properties of the molecular structures in their elementary networks Results: After partitioning the vertices based on their degrees, we calculate different degree-based topological polynomials for two distinct metal-organic networks with an escalating number of layers containing both metals and carbon-based ligand vertices. CONCLUSION: In the analysis of the metal-organic network, topological descriptors and their polynomials play an important part in modern chemistry. An analysis between the various calculated forms of the polynomials and topological descriptors through the numeric values and their graphs are also presented.

Phytopharmacological Evaluation of Different Solvent Extract/Fractions From Sphaeranthus indicus L. Flowers: From Traditional Therapies to Bioactive Compounds.

Sphaeranthus indicus L. is a medicinal herb having widespread traditional uses for treating common ailments. The present research work aims to explore the in-depth phytochemical composition and in vitro reactivity of six different polarity solvents (methanol, n-hexane, benzene, chloroform, ethyl acetate, and n-butanol) extracts/fractions of S. indicus flowers. The phytochemical composition was accomplished by determining total bioactive contents, HPLC-PDA polyphenolic quantification, and UHPLC-MS secondary metabolomics. The reactivity of the phenolic compounds was tested through the following biochemical assays: antioxidant (DPPH, ABTS, FRAP, CUPRAC, phosphomolybdenum, and metal chelation) and enzyme inhibition (AChE, BChE, α-glucosidase, α-amylase, urease, and tyrosinase) assays were performed. The methanol extract showed the highest values for phenolic (94.07 mg GAE/g extract) and flavonoid (78.7 mg QE/g extract) contents and was also the most active for α-glucosidase inhibition as well as radical scavenging and reducing power potential. HPLC-PDA analysis quantified rutin, naringenin, chlorogenic acid, 3-hydroxybenzoic acid, gallic acid, and epicatechin in a significant amount. UHPLC-MS analysis of methanol and ethyl acetate extracts revealed the presence of well-known phytocompounds; most of these were phenolic, flavonoid, and glycoside derivatives. The ethyl acetate fraction exhibited the highest inhibition against tyrosinase and urease, while the n-hexane fraction was most active for α-amylase. Moreover, principal component analysis highlighted the positive correlation between bioactive compounds and the tested extracts. Overall, S. indicus flower extracts were found to contain important phytochemicals, hence could be further explored to discover novel bioactive compounds that could be a valid starting point for future pharmaceutical and nutraceuticals applications.

Surveillance of molecular markers of antimalarial drug resistance in Plasmodium falciparum and Plasmodium vivax in Federally Administered Tribal Area (FATA), Pakistan.

This molecular epidemiological study was designed to determine the antimalarial drug resistance pattern, and the genetic diversity of malaria isolates collected from a war-altered Federally Administered Tribal Area (FATA), in Pakistan. Clinical isolates were collected from Bajaur, Mohmand, Khyber, Orakzai and Kurram agencies of FATA region between May 2017 and May 2018, and they underwent DNA extraction and amplification. The investigation of gene polymorphisms in drug resistance genes (dhfr, dhps, crt, and mdr1) of Plasmodium falciparum and Plasmodium vivax was carried out by pyrosequencing and Sanger sequencing, respectively. Out of 679 PCR-confirmed malaria samples, 523 (77%) were P. vivax, 121 (18%) P. falciparum, and 35 (5%) had mixed-species infections. All P. falciparum isolates had pfdhfr double mutants (C59R+S108N), while pfdhfr/pfdhps triple mutants (C59R+S108N+A437G) were detected in 11.5% of the samples. About 97.4% of P. falciparum isolates contained pfcrt K76T mutation, while pfmdr1 N86Y and Y184F mutations were present in 18.2% and 10.2% of the samples. P. vivax pvdhfr S58R mutation was present in 24.9% of isolates and the S117N mutation in 36.2%, while no mutation in the pvdhps gene was found. Pvmdr1 F1076L mutation was found in nearly all samples, as it was observed in 98.9% of isolates. No significant anti-folate and chloroquine resistance was observed in P. vivax; however, mutations associated with antifolate-resistance were found, and the chloroquine-resistant gene has been observed in 100% of P. falciparum isolates. Chloroquine and sulphadoxine-pyrimethamine resistance were found to be high in P. falciparum and low in P. vivax. Chloroquine could still be used for P. vivax infection but need to be tested in vivo, whereas a replacement of the artemisinin combination therapy for P. falciparum appears to be justified.

Comparative Study of Valency-Based Topological Indices for Tetrahedral Sheets of Clay Minerals.

INTRODUCTION: Intercapillary research in mathematics and other pure sciences areas has always helped humanity quantify natural phenomena. MATERIALS & METHOD: This article also contributes to which valency-based topological indices are implemented on tetrahedral sheets of clay minerals. These indices have been used for a long time and are considered the most powerful tools to quantify chemical graphs. RESULTS: The atoms in the chemical compound and the bonds between the atoms are depicted as the graph's vertices and edges, respectively. CONCLUSION: The valency (or degree) of a vertex in a graph is the number of edges incident to that vertex. In this article, various degree-based indices and their modifications are determined to check each types' significance.

An in vitro antiviral activity of iodine complexes against SARS-CoV-2.

Since the emergence of COVID-19 pandemic in China in late 2019, scientists are striving hard to explore non-toxic, viable anti-SARS-CoV-2 compounds or medicines. We determined In vitro anti-SARS-CoV-2 activity of oral formulations (syrup and capsule)of an Iodine-complex (Renessans). First, cell cytotoxicity of Renessans on the Vero cells was determined using MTT assay. Afterwards, the antiviral activity of Renessans was determined using viral inhibition assays and TCID50. For this, nontoxic concentrations of the Renessans were used. The results showed that Renessans is nontoxic to the cells up to 50 µg/mL. At 1.5 µg/mL concentration, SARS-CoV-2 production was significantly reduced to 101.43 TCID50 and 101.58 TCID50 for the syrup and capsule, respectively, as compare to virus infected control cells 106.08 TCID50 and we found the dose dependent inhibition of virus replication in the presence of Renessans. Renessans inhibited SARS-CoV-2 with an EC50 value of 0.425 µg/mL and 0.505 µg/mL for syrup and capsule, respectively. Furthermore, there was no virus detected at concentration of 50 µg/mL of Renessans. This study indicates that Renessans, containing iodine, have potential activity against SARS-CoV-2 which needs to be further investigated in human clinical trials.

Assessment of Microscopic Detection of Malaria with Nested Polymerase Chain Reaction in War-Torn Federally Administered Tribal Areas of Pakistan.

INTRODUCTION: Diagnostic accuracy of malaria is critical for early treatment, control, and elimination of malaria, especially in war-affected malaria-endemic areas. Microscopic detection of Plasmodium species has been the gold standard in remote malaria-endemic regions. However, the diagnostic accuracy is still questioned, especially in discriminating mixed and submicroscopic parasitic levels. This study was designed to evaluate the diagnostic performance of microscopic examination against nested PCR analysis in war-torn malaria-endemic Federally Administered Tribal Areas (FATA) of Pakistan. METHODS: Venous blood samples were collected from symptomatic patients for microscopic examination and nested PCR analysis from January 2016-December 2016 from five Agencies (Bajaur, Mohmand, Khyber, Orakzai and Kurram Agency) and four Frontier Regions (Peshawar, Kohat, Bannu, and Dera Ismail Khan Frontier Region) of FATA. Malaria-positive isolates were confirmed by nested PCR (targeting Plasmodium small subunit ribosomal ribonucleic acid (ssrRNA) genes) for speciation. RESULTS: Among enrolled participants, 762 were found positive for malaria parasite on microscopic examination of the blood film. Plasmodium vivax was found in 623, Plasmodium falciparum in 132 and 7 were diagnosed with mixed infection (P. vivax and P. falciparum coinfection). Nested PCR detected Plasmodium infection in 679 samples (523 P. vivax, 121 P. falciparum, and 35 mixed infections). Compared with microscopy, the sensitivity of nested PCR was 98.94%, and specificity was 98.27%, while the sensitivity and specificity of slide microscopy 89.34% and 87.99% respectively. CONCLUSION: The conventional microscopy method has low sensitivity to detect the mixed infection as compared to nested PCR. High sensitivity and specificity observed in nested PCR make this molecular tool a useful technique for monitoring, controlling, and eliminating malaria-endemic regions.

Computation and Analysis of Topological Co-Indices for Metal-Organic Compound.

A topological descriptor is a mathematical illustration of a molecular construction that relates particular physicochemical properties of primary molecular structure as well as its mathematical depiction. Topological co-indices are usually applied for quantitative structure action relationships (QSAR) and quantitative structure property relationships (QSPR). Topological co-indices are topological descriptor which consider the noncontiguous vertex set. In this study, we studyied some of the accompanied renowned topological co-indices: the 1st and 2nd Zagreb co-indices, the 1st and 2nd multiplicative Zagreb co-indices, and the F-coindex. By applying structure based examinations and deductions, we discuss the earlier stated co-indices of few synthetic atomic structures that are frequently used in clinical, synthetic, and material designing.