Combinatorial Chemistry & High Throughput Screening - Volume 25, Issue 14, 2022

Inflammation is a natural process that occurs in the organism in response to harmful external agents. Despite being considered beneficial, exaggerated cases can cause severe problems for the body. The main inflammatory manifestations are pain, increased temperature, edema, decreased mobility, and quality of life for affected individuals. Diseases such as arthritis, cancer, allergies, infections, arteriosclerosis, neurodegenerative diseases, and metabolic problems are mainly characterized by an exaggerated inflammatory response. Inflammation is related to two categories of substances: pro- and anti-inflammatory mediators. Among the pro-inflammatory mediators is Tumor Necrosis Factor-α (TNF-α). It is associated with immune diseases, cancer, and psychiatric disorders which increase its excretion. Thus, it becomes a target widely used in discovering new antiinflammatory drugs. In this context, secondary metabolites biosynthesized by plants have been used for thousands of years and continue to be one of the primary sources of new drug scaffolds against inflammatory diseases. To decrease costs related to the drug discovery process, Computer-Aided Drug Design (CADD) techniques are broadly explored to increase the chances of success. In this review, the main natural compounds derived from alkaloids, flavonoids, terpene, and polyphenols as promising TNF-α inhibitors will be discussed. Finally, we applied a molecular modeling protocol involving all compounds described here, suggesting that their interactions with Tyr⁵⁹, Tyr¹¹⁹, Tyr¹⁵¹, Leu⁵⁷, and Gly¹²¹ residues are essential for the activity. Such findings can be useful for research groups worldwide to design new anti-inflammatory TNF-α inhibitors.

Background: Cyclooxygenase (COX) and Lipoxygenase (LOX) enzymes catalyze the production of pain mediators like Prostaglandins (PGs) and Leukotrienes (LTs), respectively from arachidonic acid. Introduction: The COX and LOX enzyme modulators are responsible for the major PGs and LTs mediated complications like asthma, osteoarthritis, rheumatoid arthritis, cancer, Alzheimer’s disease, neuropathy and Cardiovascular Syndromes (CVS). Many synthetic Nonsteroidal Anti- Inflammatory Drugs (NSAIDs) used in the treatment have serious side effects like nausea, vomiting, hyperacidity, gastrointestinal ulcers, CVS, etc. Methods: The natural inhibitors of pain mediators have great acceptance worldwide due to fewer side effects on long-term uses. The present review is an extensive study of the advantages of plantbased vs synthetic inhibitors. Results: These natural COX and LOX inhibitors control inflammatory response without causing side-effect-related complicacy. Conclusion: Therefore, the natural COX and LOX inhibitors may be used as alternative medicines for the management of pain and inflammation due to their less toxicity and resistivity.

Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is a virus whose genetic material is positive single-stranded RNA, being responsible for coronavirus disease 2019 (COVID- 19), an infection that compromises the lungs and consequently the respiratory capacity of the infected individual, according to the WHO in November 2021, 249,743,428 cases were confirmed, of which 5,047,652 individuals died due to complications resulting from the infection caused by SARSCOV- 2. As the infection progresses, the individual may experience loss of smell and taste, as well as breathing difficulties, severe respiratory failure, multiple organ failure, and death. Due to this new epidemiological agent in March 2020 it was announced by the director general of the World Health Organization (WHO) a pandemic status, and with that, many research groups are looking for new therapeutic alternatives through synthetic and natural bioactives. This research is a literature review of some in silico studies involving natural products against COVID-19 inflammation published in 2020 and 2021. Work like this presents relevant information to the scientific community, boosting future research and encouraging the use of natural products for the search for new antivirals against COVID-19.

Myrica esculenta is an important ethnomedicinal plant used in the traditional system of medicine and as an important nutraceutical. Several studies on the plant justify its use in alternative systems of medicine and establish a scientific rationale for its possible therapeutic application. The plant contains a range of biologically active classes of compounds, particularly diarylheptanoids, flavonoids, terpenes, tannins, and glycosides. The nutraceutical potential of the plant can be particularly attributed to its fruit, and several studies have demonstrated the presence of carbohydrates, proteins, fats, fiber content, and minerals like sodium, potassium, calcium, manganese, iron, copper, and zinc, in it. The current review aims to provide complete insight into the phytochemistry, pharmacological potential, and nutritional potential of the plant, which would not only serve as a comprehensive source of information but also will highlight the scope of isolation and evaluation of these molecules for various disease conditions.

Neglected Tropical Diseases (NTDs) are a group of twenty (20) chronic, communicable, infectious diseases endemic to the tropics and sub-tropics climate countries, which are intimately associated with poverty, poor sanitation, limited clean water, and healthcare delivery; and dwellers live in proximity to pathogens and diseases vectors. The pathogens are protozoans, bacteria, helminths, fungi, and viruses. NTDs currently affect about one billion people globally, out of which 500 million are Africans living in rural settlements with low political voice and support. In recent years, NTDs have received little research recognition, development, and funding because more research efforts by global health stakeholders are focused on recognized diseases like cancers, hepatitis, tuberculosis, Acquired Immune-Deficiency Syndrome (AIDS), and malaria that affects most developed countries. The emergence of the viral novel COVID-19 will exacerbate the burden of NTDs on disadvantaged communities as global health efforts are again focused on COVID-19 clearance in terms of research and development to find a drug/vaccine amidst other investigations on recognized infections. This development can result in high death tolls due to NTDs if control measures are not prioritized now. This perspective addresses the need for NTDs control amidst COVID-19 clearance efforts to mitigate another viral health crisis in Africa.

The present review covers the list of approved vaccines available in India, i.e., Covaxin, Covishield, and Sputnik-V. Covaxin’s code name is BBV152. Covaxin was prepared by Hyderabad- based Bharat Biotech International Ltd. in collaboration with the National Institute of Virology (NIV) and ICMR. The effectiveness of Covaxin was found to be 78-81%. Covishield, which is available by code name AZD1222, was developed by the SII, Oxford University, and AstraZeneca. Covishield’s effectiveness was found to be 90%. The time gap between the two doses of Covaxin and Covishiled is 4-6 weeks and 12-16 weeks, respectively. One more vaccine, i.e., Sputnik V, by the code name rAd26-S and rAd5-S, was developed by Gamaleya Research Institute of Epidemiology and Microbiology, which involves an interval gap of 21 days between the two doses. Covaxin releases Anti-SARS-CoV-2 IgG, which is specific to RBD (receptor-binding domain) protein, whereas a high degree of antibody response dissipates on the 28th day of vaccination. The protective efficacy of Sputnik-V was found to be ±92.2% (95% CI ±82.6-92.3), while that of Covishield was found to be ±90 % (95% CI 68.2-98.0±, p = 0.01) 2-standard dose: (61.2%, 95% CI 42.2-76.1±). In the case of Covaxin, the rate of seroconversion was found to be 93.9% (95% CI 85.2-98.2) in the 3-μg group and 97.2% (95% CI 93.1-105.1) in the 6-μg group. No significant difference was observed in local or systemic adverse reactions of the vaccine in the groups of 3 μg and 6 μg. The protective efficacious dose of Covaxin has not yet been identified. The cellular response median SFCs PBPMC of Covishield at the standard dose in the age group of 18-55 years was found to be±1201; 55-70 years: ±758 and ≥75 years: ±975. No significant increase was observed in the per million peripheral mononuclear cells (PBPMC) after administration of the booster dose of Covishield vaccine (p = 0.45 in paired student’s t-test on the 28th day vs. the 42nd day). The cellular response to Sputnik V was found to be 100%. Higher levels of T cells CD8+, CD4+ T cells, and IFN- γ secretion were reported in all volunteers who had undergone vaccination. Cell proliferation was found as follows: CD⁴⁺: +1.5% and CD⁸⁺ : +1.3% in the lyophilized formulation and CD4+ : + 2.6% and CD8+ : +1.5% in the frozen formulation. Antigen-specific IgG geometric mean titer (GMT) levels of Covishield were found to be highest on the 28th day with 160 geometric mean ELISA units (GMEU).

The human has two lungs responsible for respiration and drug metabolism. Severe lung infection caused by bacteria, mycobacteria, viruses, fungi, and parasites may lead to lungs injury. Smoking and tobacco consumption may also produce lungs injury. Inflammatory and pain mediators are secreted by alveolar macrophages. The inflammatory mediators, such as cytokines, interleukin (IL)-1, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α, neutrophils, and fibroblasts are accumulated in the alveoli sac, which becomes infected. It may lead to hypoxia followed by severe pulmonary congestion and the death of the patient. There is an urgent need for the treatment of artificial respiration and ventilation. However, the situation may be the worst for patients suffering from lung cancer, pulmonary tuberculosis, and acute pneumonia caused by acute respiratory distress syndrome (ARDS). Re-urgency has been happening in the case of coronavirus disease of 2019 (COVID-19) patients. Therefore, it is needed to protect the lungs with the intake of natural phytomedicines. In the present review, several selected phyto components having the potential role in lung injury therapy have been discussed. Regular intake of natural vegetables and fruits bearing these constituents may save the lungs even in the dangerous attack of SARS-CoV-2 in lung cancer, pulmonary TB, and pneumatic patients.

Favipiravir is a potential antiviral drug undergoing clinical trials to manage various viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Favipiravir possesses antiviral properties against RNA viruses, including SARS-CoV-2. Unfortunately, these viruses do not have authorized antiviral drugs for the management of diseases resulting from their infection, hence the dire need to accentuate the discovery of antiviral drugs that are efficacious and have a broad spectrum. Favipiravir acts primarily by blocking inward and outward movements of the virus from cells. Favipiravir is a prodrug undergoing intracellular phosphorylation and ribosylation to form an active form, favipiravir-RTP, which binds viral RNA-dependent RNA polymerase (RdRp). Considering the novel mechanism of favipiravir action, especially in managing viral infections, it is vital to pay more attention to the promised favipiravir hold in the management of SARS-CoV-2, its efficacy, and dosage regimen, and interactions with other drugs. In conclusion, favipiravir possesses antiviral properties against RNA viruses, including COVID- 19. Favipiravir is effective against SARS-CoV-2 infection through inhibition of RdRp. Pre-clinical and large-scalp prospective studies are recommended for efficacy and long-term safety of favipiravir in COVID-19.

Since the outbreak of coronavirus disease (COVID-19) in Wuhan, China, triggered by severe acute respiratory coronavirus 2 (SARS-CoV-2) in late November 2019, spreading to more than 200 countries of the world, the ensuing pandemic to an enormous loss of lives, mainly the older population with comorbidities, like diabetes, cardiovascular disease, chronic obstructive pulmonary disease, obesity, and hypertension. Amongst these immune-debilitating diseases, SARS-CoV-2 infection is the most common in patients with diabetes due to the absence of a normal active immune system to fight the COVID-19. Recovery of patients having a history of diabetes from COVID-19 encounters several complications, and their management becomes cumbersome. For control of coronavirus, antiviral medications, glucose-lowering agents, and steroids have been carefully evaluated. In the present review, we discuss the crosstalk between SARS-CoV-2 infection and patients with a history of diabetes. We mainly emphasize the molecular factors that are involved in diabetic individuals recently infected by SARS-CoV-2 and developed COVID-19 disease. Lastly, we examine the medications available for the long-term management of diabetic patients with SARS-CoV-2 infection.

Recently, the green synthesis of metallic nanoparticles (NPs) has received tremendous attention as a simple approach. The green pathway of biogenic synthesis of metallic NPs through microbes may provide a sustainable and environmentally friendly protocol. Green technology is the most innovative technology for various biological activities and lacks toxic effects. Reports have shown the algae-mediated synthesis of metal NPs. Algae are widely used for biosynthesis as they grow fast; they produce biomass on average ten times that of plants and are easily utilized experimentally. In the future, the production of metal NPs by different microalgae and their biological activity can be explored in diverse areas such as catalysis, medical diagnosis, and anti-biofilm applications.

Background: Coronavirus is an enclosed positive-sense RNA virus with club-like spikes extending from its surface. It is most typically associated with acute respiratory infections in humans, but its capacity to infect many host species and cause multiple illnesses makes it a complicated pathogen. The frequent encounters between wild animals and humans are a typical cause of infection. The zoonotic infections SARS-CoV and MERS-CoV are among the most common causes of serious respiratory illnesses in humans. Aim: The main goal of this research was to look at gene expression profiles in human samples that were either infected with coronavirus or were not, and compare the varied expression patterns and their functional implications. Methods: The previously researched samples were acquired from a public database for this purpose, and the study was conducted, which included gene expression analysis, pathway analysis, and network-level comprehension. The results for differentially expressed genes, enriched pathways, and networks for prospective genes and gene sets are presented in the analysis. In terms of COVID-19 gene expression and its relationship to type 2 diabetes. Results: We see a lot of genes that have different gene expression patterns than normal for coronavirus infection, but in terms of pathways, it appears that there are only a few sets of functions that are affected by altered gene expression, and they are related to infection, inflammation, and the immune system. Conclusion: Based on our study, we conclude that the potential genes which are affected due to infection are NFKBIA, MYC, FOXO3, BIRC3, ICAM1, IL8, CXCL1/2/5, GADD45A, RELB, SGK1, AREG, BBC3, DDIT3/4, EGR1, MTHFD2, and SESN2 and the functional changes are mainly associated with these pathways: TNF, cytokine, NF-kB, TLR, TCR, BCR, Foxo, and TGF signaling pathways are among them and there are additional pathways such as hippo signaling, apoptosis, estrogen signaling, regulating pluropotency of stem cells, ErbB, Wnt, p53, cAMP, MAPK, PI3K-AKT, oxidative phosphorylation, protein processing in endoplasmic reticulum, prolactin signaling, adipocytokine, neurotrophine signaling, and longevity regulating pathways. SMARCD3, PARL, GLIPR1, STAT2, PMAIP1, GP1BA, and TOX genes and PI3K-Akt, focal adhesion, Foxo, phagosome, adrenergic, osteoclast differentiation, platelet activation, insulin, cytokine- cytokine interaction, apoptosis, ECM, JAK-STAT, and oxytocin signaling appear as the linkage between COVID-19 and Type-2 diabetes.

COVID-19 is considered as the most challenging in the current situation but lung cancer is also the leading cause of death in the global population. These two malignancies are among the leading human diseases and are highly complex in terms of diagnostic and therapeutic approaches as well as the most frequent and highly complex and heterogeneous in nature. Based on the latest update, it is known that the patients suffering from lung cancer, are considered to be significantly at higher risk of COVID-19 infection in terms of survival and there are a number of evidences which support the hypothesis that these diseases may share the same functions and functional components. Multi-level unwanted alterations such as (epi-)genetic alterations, changes at the transcriptional level, and altered signaling pathways (receptor, cytoplasmic, and nuclear level) are the major sources which promote a number of complex diseases and such heterogeneous level of complexities are considered as the major barrier in the development of therapeutics. With so many challenges, it is critical to understand the relationships and the common shared aberrations between them which is difficult to unravel and understand. A simple approach has been applied for this study where differential gene expression analysis, pathway enrichment, and network level understanding are carried out. Since, gene expression changes and genomic alterations are related to the COVID-19 and lung cancer but their pattern varies significantly. Based on the recent studies, it appears that the patients suffering from lung cancer and and simultaneously infected with COVID-19, then survival chance is lessened. So, we have designed our goal to understand the genes commonly overexpressed and commonly enriched pathways in case of COVID-19 and lung cancer. For this purpose, we have presented the summarized review of the previous works where the pathogenesis of lung cancer and COVID-19 infection have been focused and we have also presented the new finding of our analysis. So, this work not only presents the review work but also the research work. This review and research study leads to the conclusion that growth promoting pathways (EGFR, Ras, and PI3K), growth inhibitory pathways (p53 and STK11), apoptotic pathways (Bcl- 2/Bax/Fas), and DDR pathways and genes are commonly and dominantly altered in both the cases COVID-19 and lung cancer.

Background: The process of nucleotides modification or methyl groups addition to nucleotides is known as post-transcriptional modification (PTM). 1-methyladenosine (m1A) is a type of PTM formed by adding a methyl group to the nitrogen at the 1st position of the adenosine base. Many human disorders are associated with m1A, which is widely found in ribosomal RNA and transfer RNA. Objective: The conventional methods such as mass spectrometry and site-directed mutagenesis proved to be laborious and burdensome. Systematic identification of modified sites from RNA sequences is gaining much attention nowadays. Consequently, an extreme gradient boost predictor, m1A-Pred, is developed in this study for the prediction of modified m1A sites. Methods: The current study involves the extraction of position and composition-based properties within nucleotide sequences. The extraction of features helps in the development of the features vector. Statistical moments were endorsed for dimensionality reduction in the obtained features. Results: Through a series of experiments using different computational models and evaluation methods, it was revealed that the proposed predictor, m1A-pred, proved to be the most robust and accurate model for the identification of modified sites. Availability and Implementation: To enhance the research on m¹A sites, a friendly server was also developed, which was the final phase of this research.

Introduction: In this article, Optimal Homotopy Analysis Method (oHAM) is used for the exploration of the features of the Cattaneo-Christov model in viscous and chemically reactive nanofluid flow through a porous medium with stretching velocity at the solid/sheet surface and free stream velocity at the free surface. Methods: The two important aspects, Brownian motion and Thermophoresis, are considered. Thermal radiation is also included in the present model. Based on the heat and mass flux, the Cattaneo- Christov model is implemented on the Temperature and Concentration distributions. The governing Partial Differential Equations (PDEs) are converted into Ordinary Differential Equations (ODEs) using similarity transformations. The results are achieved using the optimal homotopy analysis method (oHAM). The optimal convergence and residual errors have been calculated to preserve the validity of the model. Results: The results are plotted graphically to see the variations in three main profiles. i.e. momentum, temperature and concentration profile. Conclusion: The outcomes indicate that skin friction enhances due to the implementation of the Darcy medium. It is also noted that the relaxation time parameter results in enhancement of the temperature distribution. Thermal radiation enhances the temperature distribution and so is the case with skin friction.

Background: The phenomenon of rotating disks involving flows serves as a crucial element in the field of fluid mechanics. Owing to its massive practical importance in engineering and industry, considerable attention is being paid to the extension of the problems associated with rotating stretching disks. In this regard, Carbon Nanotubes (CNT) are chosen as the best example of true nano technology. CNTs have an incredible range of applications due to their extraordinary characteristics. But single rotating-stretching disk with CNTs fluid flow has not been plowed yet. Objective: The objective of this work is to outstretch the study of viscous fluid with Carbon Nanotubes (CNTs) and transfer of heat due to radially stretching and rotating disk contingent to Navier slip, nonlinear radiations and convective boundary conditions. Methods: Cylindrical coordinates are utilized in the modeling and the mathematical formulation of the flow equations. These flow equations take the form of ordinary differential equations by means of similarity transformations. The emanated equations are solved by two numerical methods i.e. the shooting method and the Keller box method respectively. Xue model of carbon nanotubes is incorporated to carry out the research. Results: The acquired solutions are tabulated and precise values of the physical parameters with excellent matching results are shown. These results are juxtaposed with CNTs of multi-wall and single-wall carbon nanotubes, while water is taken as a base fluid. Conclusion: Results reveal a significant depletion in skin friction with an increase in the slip parameter. Slip, nonlinear radiation and Biot number proved as liable factors in escalating the rate of heat transfer.