Medicinal plants with anti-SARS-CoV activity repurposing for treatment of COVID-19 infection: A systematic review and meta-analysis

The novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus) has emerged as a significant threat to public health with startling drawbacks in all sectors globally. This study investigates the practicality of some medicinal plants for SARS-CoV-2 therapy using a systematic review and meta-analysis of their reported SARS-CoV-1 inhibitory potencies. Relevant data were systematically gathered from three databases, viz., Web of Science, PubMed and Scopus. The information obtained included botanical information, extraction method and extracts concentrations, as well as the proposed mechanisms. Fourteen articles describing 30 different plants met our eligibility criteria. Random effects model and subgroup analysis were applied to investigate heterogeneity. According to subgroup analysis, the substantial heterogeneity of the estimated mean based on the IC50 values reporting the most potent anti-SARS-CoV 3C-like protease (3CLpro) inhibitors (10.07 %, p < 0.0001), was significantly higher compared to the most active anti-SARS-CoV papain-like protease (PLpro) inhibitors (6.12 %, p < 0.0001). More importantly, the literature analysis revealed that fruit extracts of Rheum palmatum Linn. and the compound cryptotanshinone isolated from the root of Salvia miltiorrhiza (IC50 = of 0.8 ± 0.2 µmol L–1) were excellent candidates for anti-SARS-CoV targeting PLpro. Meanwhile, iguesterin (IC50 = 2.6 ± 0.6 µmol L–1) isolated from the bark of Tripterygium regelii emerged as the most excellent candidate for anti-SARS-CoV targeting 3CLpro. The present systematic review and meta-analysis provide valuable and comprehensive information about potential medicinal plants for SARS-CoV-2 inhibition. The chemotypes identified herein can be adopted as a starting point for developing new drugs to contain the novel virus

Promising inhibitors against main protease of SARS CoV-2 from medicinal plants: In silico identification

Some compounds reported as active against SARS CoV were selected, and docking studies were performed using the main protease of SARS CoV-2 as the receptor. The docked complex analysis shows that the ligands selectively bind with the target residues and binding affinity of amentoflavone (‒10.1 kcal mol‒1), isotheaflavin-3\u27-gallate (‒9.8 kcal mol‒1), tomentin A and D (‒8.0 and ‒8.8 kcal mol‒1), theaflavin-3,3\u27-digallate (‒8.6 kcal mol‒1), papyriflavonol A (‒8.4 kcal mol‒1), iguesterin (‒8.0 kcal mol‒1) and savinin (‒8.3 kcal mol‒1) were ranked above the binding affinity of the reference, co-crystal ligand, ML188, a furan-2-carboxamide-based compound. To pinpoint the drug-like compound among the top-ranked compounds, the Lipinski’s rule of five and pharmacokinetic properties of all the selected compounds were evaluated. The results detailed that savinin exhibits high gastrointestinal absorption and can penetrate through the blood-brain barrier. Also, modifying these natural scaffolds with excellent binding affinity as new anti-SARS CoV agents may lead to discovering novel drug-like candidates with promising safety profiles

A Review of the Recent Development in the Synthesis and Biological Evaluations of Pyrazole Derivatives

Pyrazoles are five-membered heterocyclic compounds that contain nitrogen. They are an important class of compounds for drug development; thus, they have attracted much attention. In the meantime, pyrazole derivatives have been synthesized as target structures and have demonstrated numerous biological activities such as antituberculosis, antimicrobial, antifungal, and anti-inflammatory. This review summarizes the results of published research on pyrazole derivatives synthesis and biological activities. The published research works on pyrazole derivatives synthesis and biological activities between January 2018 and December 2021 were retrieved from the Scopus database and reviewed accordingly

A Review of the Recent Developments of Molecular Hybrids Targeting Tubulin Polymerization

Microtubules are cylindrical protein polymers formed from αβ-tubulin heterodimers in the cytoplasm of eukaryotic cells. Microtubule disturbance may cause cell cycle arrest in the G2/M phase, and anomalous mitotic spindles will form. Microtubules are an important target for cancer drug action because of their critical role in mitosis. Several microtubule-targeting agents with vast therapeutic advantages have been developed, but they often lead to multidrug resistance and adverse side effects. Thus, single-target therapy has drawbacks in the effective control of tubulin polymerization. Molecular hybridization, based on the amalgamation of two or more pharmacophores of bioactive conjugates to engender a single molecular structure with enhanced pharmacokinetics and biological activity, compared to their parent molecules, has recently become a promising approach in drug development. The practical application of combined active scaffolds targeting tubulin polymerization inhibitors has been corroborated in the past few years. Meanwhile, different designs and syntheses of novel anti-tubulin hybrids have been broadly studied, illustrated, and detailed in the literature. This review describes various molecular hybrids with their reported structural–activity relationships (SARs) where it is possible in an effort to generate efficacious tubulin polymerization inhibitors. The aim is to create a platform on which new active scaffolds can be modeled for improved tubulin polymerization inhibitory potency and hence, the development of new therapeutic agents against cancer

Unveiling of Pyrimidindinones as Potential Anti-Norovirus Agents&mdash;A Pharmacoinformatic-Based Approach

The RNA-dependent RNA polymerase (RdRp) receptor is an attractive target for treating human norovirus (HNV). A computer-aided approach like e-pharmacophore, molecular docking, and single point energy calculations were performed on the compounds retrieved from the Development Therapeutics Program (DTP) AIDS Antiviral Screen Database to identify the antiviral agent that could target the HNV RdRp receptor. Induced-fit docking (IFD) results showed that compounds ZINC1617939, ZINC1642549, ZINC6425208, ZINC5887658 and ZINC32068149 bind with the residues in the active site-B of HNV RdRp receptor via hydrogen bonds, salt bridge, and electrostatic interactions. During the molecular dynamic simulations, compounds ZINC6425208, ZINC5887658 and ZINC32068149 displayed an unbalanced backbone conformation with HNV RdRp protein, while ZINC1617939 and ZINC1642549 maintained stability with the protein backbone when interacting with the residues. Hence, the two new concluding compounds discovered by the computational approach can be used as a chemotype to design promising antiviral agents aimed at HNV RdRp

Mapping Scientific Productivity Trends and Hotspots in Remdesivir Research Publications: A Bibliometric Study from 2016 to 2021

In response to global efforts to control and exterminate infectious diseases, this study aims to provide insight into the productivity of remdesivir research and highlight future directions. To achieve this, there is a need to summarize and curate evidence from the literature. As a result, this study carried out comprehensive scientific research to detect trends in published articles related to remdesivir using a bibliometric analysis. Keywords associated with remdesivir were used to access pertinent published articles using the Scopus database. A total of 5321 research documents were retrieved, primarily as novel research articles (n = 2440; 46%). The number of publications increased exponentially from 2020 up to the present. The papers published by the top 12 institutions focusing on remdesivir accounted for 25.69% of the overall number of articles. The USA ranked as the most productive country, with 906 documents (37.1%), equivalent to one-third of the global publications in this field. The most productive institution was Icahn School of Medicine, Mount Sinai, in the USA (103 publications). The New England Journal of Medicine was the most cited, with an h-index of 13. The publication of research on remdesivir has gained momentum in the past year. The importance of remdesivir suggests that it needs continued research to help global health organizations detect areas requiring instant action to implement suitable measures. Furthermore, this study offers evolving hotspots and valuable insights into the scientific advances in this field and provides scaling-up analysis and evidence diffusion on remdesivir

An Overview of the Biological Evaluation of Selected Nitrogen-Containing Heterocycle Medicinal Chemistry Compounds

Heterocyclic compounds are a class of compounds of natural origin with favorable properties and hence have major pharmaceutical significance. They have an exceptional adroitness favoring their use as diverse smart biomimetics, in addition to possessing an active pharmacophore in a complex structure. This has made them an indispensable motif in the drug discovery field. Heterocyclic compounds are usually classified according to the ring size, type, and the number of heteroatoms present in the ring. Among different heterocyclic ring systems, nitrogen heterocyclic compounds are more abundant in nature. They also have considerable pharmacological significance. This review highlights recent pioneering studies in the biological assessment of nitrogen-containing compounds, namely: triazoles, tetrazoles, imidazole/benzimidazoles, pyrimidines, and quinolines. It explores publications between April 2020 and February 2022 and will benefit researchers in medicinal chemistry and pharmacology. The present work is organized based on the size of the heterocyclic ring

Determination of Potentially Harmful Element (PHE) Distribution in Water Bodies in Krugersdorp, a Mining City in the West Rand, Gauteng Province, South Africa

The town of Krugersdorp in South Africa is the locus of an important wildlife game reserve, the Krugersdorp Game Reserve (KGR), which is juxtaposed by the (&lt;1000 m) down-gradient of the large-scale gold mining outfits of Mintails Mogale Gold (MMG) and Rand Uranium (RU). The aim of the study was to determine the concentration levels of potentially harmful elements (PHEs) that have accumulated due to post-mining activities in the local water bodies in Krugersdorp and to use these data as a prerequisite and basis for formulation of the most appropriate remediation measures. Thirty water samples were collected and analysed in situ for: water temperature, pH, dissolved oxygen (mgl−1), dissolved oxygen (%), total dissolved solids (TDS), oxidation/reduction potential (ORP), and electrical conductivity (EC). This was later followed by laboratory analyses of aliquots of the water samples by ICP-MS for twelve PHEs whose concentration ranges were: As (0.70–32.20), Ag (0.16–105.00), Al (1.00–41.00), Co (0.07–6.16), Cr (1.60–5.00), Cu (0.80–8.00), Fe (23.00–117.00), Mn (0.14–12 255.00), Ni (0.20–7.00), Pb (0.80–6.30), V (1.90–55.20), and Zn (2.20–783.00). Areas of the town where excessive concentration levels of these elements have negatively impacted the health of its wildlife population and surrounding ecosystems are identified, and credible mitigation measures proffered

Analysis of the Distribution of Some Potentially Harmful Elements (PHEs) in the Krugersdorp Game Reserve, Gauteng, South Africa

The Mintails Mogale Gold (MMG) and the Rand Uranium (RU) are two large-scale mining consortiums active in re-mining old tailings dams and dumps in Krugersdorp and are a source of mine discharge feed into the Krugersdorp Game Reserve (KGR). This has resulted in a noticeable accumulation of potentially harmful elements (PHEs) over a number of years. Efforts were implemented to interpret the concentration levels of PHEs in soils of the study areas of which a total of 36 georeferenced soil samples were collected (in triplicate) from the MMG, RU and KGR, including samples from farmlands and waterways adjacent to the mining sites. Samples were then analysed by both inductively coupled plasma optical emission spectrometry (ICP-OES) and inductively coupled plasma mass spectrometry (ICP-MS) for 36 elements. From the 36 elements of this study, detailed evaluations of the occurrence of 12 selected elements were discussed. The geochemical landscape at the KGR is shown to be in flux. The major mediating influences on the behaviour of As, Co, Cu, Hg and Pb, as they enter the KGR largely in the form of acid mine drainage (AMD), are the geological substrate (mostly in carbonate form). Analysis of the soils showed high levels of contamination for As and Co in ppm. The mean maximum of As ranged from (5.00&ndash;170.30) with the highest level found in the Krugersdorp site. The mean maximum of Co ranged from (46.00&ndash;102.30) with the highest level found in MMG. All of these values were well above the recommended maximum acceptable concentration (MAC) values, i.e., As (15&ndash;20) and Co (20&ndash;50). The mean maximum values for Pb (12.40&ndash;92.30); Cu (18.50&ndash;115.30) and Hg (12.40&ndash;92.30) content in surface soils of all four segments studied falls well within the MAC range for agricultural soils i.e., Cu (60&ndash;150); Hg (0.5&ndash;5) and Pb (20&ndash;300)