Molecular Docking and Dynamics Simulation Revealed the Potential Inhibitory Activity of ACEIs Against SARS-CoV-2 Targeting the h ACE2 Receptor
The rapid and global spread of a new human coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has produced an immediate urgency to discover promising targets for the treatment of COVID-19.
Here, we consider drug repurposing as an attractive approach that can facilitate the drug discovery process by repurposing existing pharmaceuticals to treat illnesses other than their primary indications. We review current information concerning the global health issue of COVID-19 including promising approved drugs, e.g., human angiotensin-converting enzyme inhibitors (hACEIs).
Besides, we describe computational approaches to be used in drug repurposing and highlight examples of in-silico studies of drug development efforts against SARS-CoV-2. Alacepril and lisinopril were found to interact with human angiotensin-converting enzyme 2 (hACE2), the host entranceway for SARS-CoV-2 spike protein, through exhibiting the most acceptable rmsd_refine values and the best binding affinity through forming a strong hydrogen bond with Asn90, which is assumed to be essential for the activity, as well as significant extra interactions with other receptor-binding residues.
Furthermore, molecular dynamics (MD) simulations followed by calculation of the binding free energy were also carried out for the most promising two ligand-pocket complexes from docking studies (alacepril and lisinopril) to clarify some information on their thermodynamic and dynamic properties and confirm the docking results as well.
These results we obtained probably provided an excellent lead candidate for the development of therapeutic drugs against COVID-19. Eventually, animal experiments and accurate clinical trials are needed to confirm the potential preventive and treatment effect of these compounds.
Revision and phylogeny of the genus Loxoneptera Hampson, 1896 (Lepidoptera, Crambidae, Pyraustinae), based on morphology and molecular data
The genus Loxoneptera Hampson, 1896 is revised based on external appearance and genitalia. It is comprised of eleven species, of which three are described as new species from China: L. crassiuncata Chen & Zhang, sp. nov., L. triangularis Chen & Zhang, sp. nov., and L. rectacerosa Chen & Zhang, sp. nov.; six species are proposed as new combinations: L. carnealis (Swinhoe, 1895), comb. nov., L. medialis (Caradja, 1925), comb. nov., L. pentasaris (Meyrick, 1932), comb. nov., L. bipunctalis (Hampson, 1912), comb. nov., L. brevipalpis (Snellen, 1890), comb. nov., and L. dichroma (Moore, 1888), comb. nov. A new replacement name, L. hampsoni Chen & Zhang, nom. nov., is proposed for L. carnealis Hampson, 1896, the type species of the genus, because it is a secondary homonym of L. carnealis (Swinhoe, 1895), comb. nov. External characters and genitalia morphology of all species are figured. Nucleotide sequences of COI, 16S rRNA, 28S rRNA, and EF-1α were used for the molecular analysis and phylogeny of Loxoneptera species.
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Ultra-high Magnification Endocytoscopy and Molecular Markers for Defining Endoscopic and Histologic Remission in Ulcerative Colitis-An Exploratory Study to Define Deep Remission
Background: Endoscopic and histological remission are both important treatment goals in patients with ulcerative colitis (UC). We aimed to define cellular architecture, expression of molecular markers, and their correlation with endoscopic scores assessed by ultra-high magnification endocytoscopy (ECS) and histological scores.
Methods: Patients with UC (n = 29) were prospectively recruited. The correlation among ECS score (ECSS), Mayo endoscopic score (MES), and histological scores were determined. Area under curve were plotted to determine the best thresholds for ECSS that predicted histological remission by Robarts (RHI) and Nancy Histological Index (NHI).
Soluble analytes relevant to inflammation were measured in serum and mucosal culture supernatants using ProcartaPlex Luminex assays and studied by partial least square discriminant analysis and logistic model. Mucosal RNA sequencing and bioinformatics analysis were performed to define differentially expressed genes/pathways.
Results: Endocytoscope scoring system correlated strongly with RHI (r = 0.89; 95% CI, 0.51-0.98) and NHI (r = 0.86; 95% CI, 0.42-0.98) but correlated poorly with MES (r = 0.28; 95% CI, 0.27-0.70). We identified soluble brain-derived neurotrophic factors (BDNF), macrophage inflammatory proteins (MIP-1 α), and soluble vascular cell adhesion molecule 1 (sVCAM-1) predicted histological remission.
Mucosal biopsy cultures also identified sVCAM-1 associated with healed mucosa. RNA-seq analysis identified gene expressions shared between ECSS, RHI, or NHI defined healing. A number of gene expressions and pathways were identified including inflammation and metabolic and tumor suppressors that discriminated healed from nonhealed mucosa.
Conclusions: Endocytoscopy represents an interesting tool that may sit between endoscopy and histology-but closer to the latter-identifying gene expression markers and pathways that are also identified by histology.
Description: This gene encodes a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor family. These growth factors are mitogens for cells of mesenchymal origin. The identity of the growth factor bound to a receptor monomer determines whether the functional receptor is a homodimer or a heterodimer, composed of both platelet-derived growth factor receptor alpha and beta polypeptides. Studies suggest that this gene plays a role in organ development, wound healing, and tumor progression. Mutations in this gene have been associated with idiopathic hypereosinophilic syndrome, somatic and familial gastrointestinal stromal tumors, and a variety of other cancers.
Description: This gene encodes a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor family. These growth factors are mitogens for cells of mesenchymal origin. The identity of the growth factor bound to a receptor monomer determines whether the functional receptor is a homodimer or a heterodimer, composed of both platelet-derived growth factor receptor alpha and beta polypeptides. Studies suggest that this gene plays a role in organ development, wound healing, and tumor progression. Mutations in this gene have been associated with idiopathic hypereosinophilic syndrome, somatic and familial gastrointestinal stromal tumors, and a variety of other cancers.
Description: This gene encodes a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor family. These growth factors are mitogens for cells of mesenchymal origin. The identity of the growth factor bound to a receptor monomer determines whether the functional receptor is a homodimer or a heterodimer, composed of both platelet-derived growth factor receptor alpha and beta polypeptides. Studies suggest that this gene plays a role in organ development, wound healing, and tumor progression. Mutations in this gene have been associated with idiopathic hypereosinophilic syndrome, somatic and familial gastrointestinal stromal tumors, and a variety of other cancers.
Description: This gene encodes a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor family. These growth factors are mitogens for cells of mesenchymal origin. The identity of the growth factor bound to a receptor monomer determines whether the functional receptor is a homodimer or a heterodimer, composed of both platelet-derived growth factor receptor alpha and beta polypeptides. Studies suggest that this gene plays a role in organ development, wound healing, and tumor progression. Mutations in this gene have been associated with idiopathic hypereosinophilic syndrome, somatic and familial gastrointestinal stromal tumors, and a variety of other cancers.
Description: This gene encodes a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor family. These growth factors are mitogens for cells of mesenchymal origin. The identity of the growth factor bound to a receptor monomer determines whether the functional receptor is a homodimer or a heterodimer, composed of both platelet-derived growth factor receptor alpha and beta polypeptides. Studies suggest that this gene plays a role in organ development, wound healing, and tumor progression. Mutations in this gene have been associated with idiopathic hypereosinophilic syndrome, somatic and familial gastrointestinal stromal tumors, and a variety of other cancers.
Description: This gene encodes a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor family. These growth factors are mitogens for cells of mesenchymal origin. The identity of the growth factor bound to a receptor monomer determines whether the functional receptor is a homodimer or a heterodimer, composed of both platelet-derived growth factor receptor alpha and beta polypeptides. Studies suggest that this gene plays a role in organ development, wound healing, and tumor progression. Mutations in this gene have been associated with idiopathic hypereosinophilic syndrome, somatic and familial gastrointestinal stromal tumors, and a variety of other cancers.
Description: A Monoclonal antibody against Human PDGFRB / PDGFR Beta (clone 42G12). The antibodies are raised in Mouse and are from clone 42G12. This antibody is applicable in WB and IHC-P
Description: A Monoclonal antibody against Human T. The antibodies are raised in Mouse and are from clone 394CT14.1.4. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human FYN. The antibodies are raised in Mouse and are from clone 1302CT390.118.237. This antibody is applicable in WB, FC, IHC-P, E
Monoclonal JUN antibody , Clone: 1306CT545.208.117
Description: A Monoclonal antibody against Human JUN . The antibodies are raised in Mouse and are from clone 1306CT545.208.117. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human PHB. The antibodies are raised in Mouse and are from clone 1215CT487.109.106. This antibody is applicable in WB and IHC-P, E
Description: A Monoclonal antibody against Human SP1. The antibodies are raised in Mouse and are from clone 1326CT463.109.176. This antibody is applicable in WB, FC, IF, E
Description: A Monoclonal antibody against Human VCP. The antibodies are raised in Mouse and are from clone 1344CT150.163.114. This antibody is applicable in WB and IF, E
Description: A Monoclonal antibody against Human ATG5. The antibodies are raised in Mouse and are from clone 1358CT289.125.123. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human CDK5. The antibodies are raised in Mouse and are from clone 1321CT281.130.129. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human CDK5. The antibodies are raised in Mouse and are from clone 1321CT281.130.129. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human CD74. The antibodies are raised in Mouse and are from clone 1267CT820.116.140.154. This antibody is applicable in WB, FC, E
Description: A Monoclonal antibody against Human USP5. The antibodies are raised in Mouse and are from clone 1340CT704.170.140. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human RAC1. The antibodies are raised in Mouse and are from clone 1301CT276.121.104. This antibody is applicable in WB, FC, IHC-P, E
Description: A Monoclonal antibody against Human WNT4. The antibodies are raised in Mouse and are from clone 1698CT540.169.185. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human FLNA. The antibodies are raised in Mouse and are from clone 1273CT424.104.153. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human SRC. The antibodies are raised in Mouse and are from clone 1602CT774.225.92. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human CD138. The antibodies are raised in Mouse and are from clone 531CT15.4.1;531CT15.1.4. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human CRYAB. The antibodies are raised in Mouse and are from clone 1329CT523.140.120. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human CREB1. The antibodies are raised in Mouse and are from clone 1335CT115.203.189. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human NFKB1. The antibodies are raised in Mouse and are from clone 1298CT792.105.117.133. This antibody is applicable in WB, FC, IHC-P, E
Description: A Monoclonal antibody against Human USP25. The antibodies are raised in Mouse and are from clone 1277CT376.106.171. This antibody is applicable in WB, E
Monoclonal AURKA Antibody, Clone: 1364CT291.108.155
Description: A Monoclonal antibody against Human AURKA . The antibodies are raised in Mouse and are from clone 1364CT291.108.155. This antibody is applicable in WB and IHC-P, E
Description: A Monoclonal antibody against Human APEX1. The antibodies are raised in Mouse and are from clone 1518CT337.123.86.269.232. This antibody is applicable in IF, IHC-P, WB, E
Description: A Monoclonal antibody against Human YWHAZ. The antibodies are raised in Mouse and are from clone 1314CT423.108.153.173.140. This antibody is applicable in WB and IF, E
Description: A Monoclonal antibody against Human PPARA. The antibodies are raised in Mouse and are from clone 1331CT894.186.143. This antibody is applicable in WB, FC, IF, IHC-P, E
Description: A Monoclonal antibody against Human Stat3. The antibodies are raised in Mouse and are from clone 1200CT146.104.153. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human STAT3. The antibodies are raised in Mouse and are from clone 1200CT146.104.153. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human EPHA6. The antibodies are raised in Mouse and are from clone 1426CT591.205.91.119. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human AKT2. The antibodies are raised in Mouse and are from clone 1623CT791.157.67.66. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human CDK5. The antibodies are raised in Mouse and are from clone 1552CT262.105.8. This antibody is applicable in IF, FC, IHC-P, WB, E
Description: A Monoclonal antibody against Human CDK4. The antibodies are raised in Mouse and are from clone 1529CT850.162.73. This antibody is applicable in IHC-P, WB, E
Description: A Monoclonal antibody against Human VAV1. The antibodies are raised in Mouse and are from clone 1582CT802.383.58. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human MITF. The antibodies are raised in Mouse and are from clone 1607CT834.207.47. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human SUFU. The antibodies are raised in Mouse and are from clone 1783CT536.263.29. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human GLS2. The antibodies are raised in Mouse and are from clone 1758CT879.217.60. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human Musk. The antibodies are raised in Mouse and are from clone 1429CT456.173.44. This antibody is applicable in WB and IHC-P, E
Anti Beta-Estradiol Monoclonal Antibody (1977CT128.130.83)
Description: A Monoclonal antibody against Human FER. The antibodies are raised in Mouse and are from clone 1457CT181.12.17. This antibody is applicable in IHC-P, WB, E
Description: A Monoclonal antibody against Human FZR. The antibodies are raised in Mouse and are from clone 1621CT637.76.67. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human P53. The antibodies are raised in Mouse and are from clone 1711CT184.18.1. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human CBL. The antibodies are raised in Mouse and are from clone 1762CT401.80.60. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human MYC. The antibodies are raised in Mouse and are from clone 1788CT320.61.28. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human HCK. The antibodies are raised in Mouse and are from clone 1508CT602.13.1. This antibody is applicable in IF, WB, E
Description: A Monoclonal antibody against Human LCK. The antibodies are raised in Mouse and are from clone 1526CT823.75.16. This antibody is applicable in IF, FC, IHC-P, WB, E
Description: A Monoclonal antibody against Human RYK. The antibodies are raised in Mouse and are from clone 1671CT575.42.61. This antibody is applicable in FC, WB, E
Description: A Monoclonal antibody against Human VCP. The antibodies are raised in Mouse and are from clone 1563CT163.48.77. This antibody is applicable in WB and IHC-P, IF, FC, E
Description: A Monoclonal antibody against Human CDKN1B. The antibodies are raised in Mouse and are from clone 1373CT407.103.103. This antibody is applicable in WB and IHC-P, E
Description: A Monoclonal antibody against Human SQSTM1. The antibodies are raised in Mouse and are from clone 1336CT763.152.125. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human DPYSL5. The antibodies are raised in Mouse and are from clone 1503CT789.209.250.52. This antibody is applicable in IF, WB, E
Description: A Monoclonal antibody against Human RPTOR. The antibodies are raised in Mouse and are from clone 1411CT316.2.151.34. This antibody is applicable in WB and IHC-P, E
Description: A Monoclonal antibody against Human TIMP2. The antibodies are raised in Mouse and are from clone 1554CT494.262.47. This antibody is applicable in IF, FC, IHC-P, WB, E
Description: A Monoclonal antibody against Human RNF20. The antibodies are raised in Mouse and are from clone 1594CT552.128.36. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human RRAS2. The antibodies are raised in Mouse and are from clone 1578CT130.349.47.14. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human CADH1. The antibodies are raised in Mouse and are from clone 1579CT577.150.80. This antibody is applicable in IHC-P, WB, E
Description: A Monoclonal antibody against Human RAB20. The antibodies are raised in Mouse and are from clone 1694CT210.142.16. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human RAB20. The antibodies are raised in Mouse and are from clone 1694CT210.218.54. This antibody is applicable in FC, WB, E
Description: A Monoclonal antibody against Human MKRN2. The antibodies are raised in Mouse and are from clone 1556CT631.230.55.49. This antibody is applicable in IHC-P, FC, WB, E
Description: A Monoclonal antibody against Human RAB18. The antibodies are raised in Mouse and are from clone 1573CT811.119.39. This antibody is applicable in FC, WB, E
Description: A Monoclonal antibody against Human PPP2R1B. The antibodies are raised in Mouse and are from clone 1496CT356.164.25.226. This antibody is applicable in IF, IHC-P, FC, WB, E
Description: A Monoclonal antibody against Human ATG3. The antibodies are raised in Mouse and are from clone 1377CT239.6.1.12. This antibody is applicable in WB and IHC-P, E
Description: A Monoclonal antibody against Human AGXT. The antibodies are raised in Mouse and are from clone 1739CT804.82.83.1. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human DDR1. The antibodies are raised in Mouse and are from clone 1464CT339.1.54. This antibody is applicable in IHC-P, WB, E
Description: A Monoclonal antibody against Human CDK2. The antibodies are raised in Mouse and are from clone 1534CT665.36.16. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human IRF3. The antibodies are raised in Mouse and are from clone 1522CT766.58.24. This antibody is applicable in IF, FC, IHC-P, WB, E
Description: A Monoclonal antibody against Human YES1. The antibodies are raised in Mouse and are from clone 1612CT505.7.50. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human ETS1. The antibodies are raised in Mouse and are from clone 1601CT512.35.61. This antibody is applicable in FC, WB, E
Description: A Monoclonal antibody against Human CDK1. The antibodies are raised in Mouse and are from clone 1644CT107.30.27. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human FAT1. The antibodies are raised in Mouse and are from clone 1634CT464.1.9. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human FAT4. The antibodies are raised in Mouse and are from clone 1654CT645.1.70. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human TPM3. The antibodies are raised in Mouse and are from clone 1649CT306.29.13. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human PCNA. The antibodies are raised in Mouse and are from clone 1655CT506.10.26. This antibody is applicable in IHC-P, FC, WB, E
Description: A Monoclonal antibody against Human CYLD. The antibodies are raised in Mouse and are from clone 1667CT857.3.6.1. This antibody is applicable in FC, WB, E
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Cellular and Molecular Processes in Pulmonary Hypertension
Pulmonary hypertension (PH) is a progressive lung disease characterized by persistent pulmonary vasoconstriction. Another well-recognized characteristic of PH is the muscularization of peripheral pulmonary arteries.
This pulmonary vasoremodeling manifests in medial hypertrophy/hyperplasia of smooth muscle cells (SMCs) with possible neointimal formation. The underlying molecular processes for these two major vascular responses remain not fully understood.
On the other hand, a series of very recent studies have shown that the increased reactive oxygen species (ROS) seems to be an important player in mediating pulmonary vasoconstriction and vasoremodeling, thereby leading to PH. Mitochondria are a primary site for ROS production in pulmonary artery (PA) SMCs, which subsequently activate NADPH oxidase to induce further ROS generation, i.e., ROS-induced ROS generation.
ROS control the activity of multiple ion channels to induce intracellular Ca2+ release and extracellular Ca2+ influx (ROS-induced Ca2+ release and influx) to cause PH. ROS and Ca2+ signaling may synergistically trigger an inflammatory cascade to implicate in PH.
Accordingly, this paper explores the important roles of ROS, Ca2+, and inflammatory signaling in the development of PH, including their reciprocal interactions, key molecules, and possible therapeutic targets.
