Psychoactive substance abuse among commercial bus drivers in Umuahia, Abia State, South-Eastern Nigeria: an uncontrolled "epidemic" with attendant road traffic crashes.

BACKGROUND INFORMATION: The unprecedented depletion of the productive workforce has been majorly attributed to road traffic crashes (RTCs). The attendant consequences of this depletion have been found to constitute a serious global public health challenge, with the use of psychoactive substances among drivers implicated in every three of five motor vehicle accidents. Hence, this study assessed the pattern and explored the determinants of substance abuse among commercial bus drivers in Umuahia, Abia State. METHODS: A descriptive cross-sectional design was used for the study. Four hundred commercial bus drivers were recruited from selected motor parks in Abia-state, using a multistage sampling technique from October to December 2020. A pretested, interviewer-administered questionnaire was administered to obtain socio-demographics and information on substance abuse. Data were analyzed using IBM SPSS version 25; bivariate analysis was done using Chi-square. The level of significance was at 5%. RESULTS: The mean age of the respondents was 40.03 ± 10.50 years. The proportion of respondents who had ever abused a psychoactive substance was 74.6%. The most commonly abused substances among drivers include alcohol (51%), cigarettes (27%), and alcoholic herbal mixtures (16%). The study participants had poor knowledge (54.5%) and poor perception (63.2%) about psychoactive substance abuse. Among the factors found to be significantly associated with substance abuse among respondents were ethnicity (p = 0.002), religion (p = 0.009) and monthly income (p = 0.013) of the respondents, poor knowledge (p < 0.001) and poor perception (p < 0.001). However, this study found religion (p = 0.031; OR = 5.469; CI = 1.170 to 25.555), knowledge (p < 0.001; OR = 4.21; CI = 2.201 to 8.287) and perception (p < 0.001; OR = 9.828; CI = 15.572 to 65.052) as factors that were associated with the higher likelihood of psychoactive substance abuse. CONCLUSION: Religion, poor knowledge and perception were associated with the higher likelihood of psychoactive substance abuse among commercial bus drivers. Targeting commercial bus drivers for educational interventions and using religious leaders as conveyor belts may reduce the use of psychoactive substances among them.

Discovery of Novel HSP27 Inhibitors as Prospective Anti-Cancer Agents Utilizing Computer-Assisted Therapeutic Discovery Approaches.

Heat shock protein 27 (HSP27) is a protein that works as a chaperone and an antioxidant and is activated by heat shock, environmental stress, and pathophysiological stress. However, HSP27 dysregulation is a characteristic of many human cancers. HSP27 suppresses apoptosis and cytoskeletal reorganization. As a result, it is recognized as a critical therapeutic target for effective cancer therapy. Despite the effectiveness of multiple HSP27 inhibitors in pre-clinical investigations and clinical trials, no HSP27 inhibitor has progressed to the anticancer phase of the development. These difficulties have mostly been attributable to existing anticancer therapies' inability to target oncogenic HSP27. Highly selective HSP27 inhibitors with higher effective-ness and low toxicity led to the development of combination techniques that include computer-aided assisted therapeutic discovery and design. This study emphasizes the most recent results and roles of HSP27 in cancer and the potential for utilizing an anticancer chemical database to uncover novel compounds to inhibit HSP27.

Novel Molecules derived from 3-O-(6-galloylglucoside) inhibit Main Protease of SARS-CoV 2 In Silico.

The ongoing pandemic caused by the severe acute respiratory syndrome 2 (SARS-CoV 2) has led to more than 168 million confirmed cases with 3.5 million deaths as at 28th May, 2021 across 218 countries. The virus has a cysteine protease called main protease (Mpro) which is significant to it life cycle, tagged as a suitable target for novel antivirals. In this computer-assisted study, we designed 100 novel molecules through an artificial neural network-driven platform called LigDream (https://playmolecule.org/LigDream/) using 3-O-(6-galloylglucoside) as parent molecule for design. Druglikeness screening of the molecules through five (5) different rules was carried out, followed by a virtual screening of those molecules without a single violation of the druglike rules using AutoDock Vina against Mpro. The in silico pharmacokinetic features were predicted and finally, quantum mechanics/molecular mechanics (QM/MM) study was carried out using Molecular Orbital Package 2016 (MOPAC2016) on the overall hit compound with controls to determine the stability and reactivity of the lead molecule. The findings showed that eight (8) novel molecules violated none of the druglikeness rules of which three (3) novel molecules (C33, C35 and C54) showed the utmost binding affinity of -8.3 kcal/mol against Mpro; C33 showed a good in silico pharmacokinetic features with acceptable level of stability and reactively better than our controls based on the quantum chemical descriptors analysis. However, there is an urgent need to carry out more research on these novel molecules for the fight against the disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11696-021-01899-y.

In-silico analysis of the inhibition of the SARS-CoV-2 main protease by some active compounds from selected African plants.

OBJECTIVES: Over the years, Azadirachta indica, Mangifera indica, and Moringa oleifera have been shown to possess some antiviral characteristics. This study applies molecular docking techniques to assess inhibitory effects of some bioactive compounds from the plants mentioned above against the main protease (Mpro), a key protein involved in SARS-CoV-2 replication. Furthermore, adsorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles for screened compounds were predicted in silico. METHODS: The crystal structure of Mpro was retrieved from the Protein Data Bank, while the plant bioactive compounds were retrieved from Pubchem. Drug-likeness of the selected compounds and a control drug (hydroxychloroquine) were assessed, and the compounds that satisfied the drug-likeness rule were docked against Mpro. The docked complexes were analyzed using LigPlot and the protein-ligand profiler server. The top five compound hits were subjected to ADMET screening using the ADMETSar server. RESULTS: A total of 17 out of 22 screened compounds passed Lipinski's assessment. Additionally, the most active compounds from the investigated plants exhibited relative inhibitory potentials against Mpro compared with hydroxychloroquine, which alludes to their possible involvement in inhibiting the SARS-CoV-2 main protease replication process. CONCLUSIONS: In our study, most of the active phytocomponents of the investigated plants exhibited relative inhibitory potentials against Mpro of SARS-CoV-2 and preferred pharmacological features when compared with hydroxychloroquine. These findings indicate these compounds are potentially antiviral candidates against SARS-CoV-2.

Molecular docking studies of some selected gallic acid derivatives against five non-structural proteins of novel coronavirus.

BACKGROUND: The World Health Organization has recently declared a new coronavirus disease (COVID-19) a pandemic and a global health emergency. The pressure to produce drugs and vaccines against the ongoing pandemic has resulted in the use of some drugs such as azithromycin, chloroquine (sulfate and phosphate), hydroxychloroquine, dexamethasone, favipiravir, remdesivir, ribavirin, ivermectin, and lopinavir/ritonavir. However, reports from some of the clinical trials with these drugs have proved detrimental on some COVID-19 infected patients with side effects more of which cardiomyopathy, cardiotoxicity, nephrotoxicity, macular retinopathy, and hepatotoxicity have been recently reported. Realizing the need for potent and harmless therapeutic compounds to combat COVID-19, we attempted in this study to find promising therapeutic compounds against the imminent threat of this virus. In this current study, 16 derivatives of gallic acid were docked against five selected non-structural proteins of SARS-COV-2 known to be a good target for finding small molecule inhibitors against the virus, namely, nsp3, nsp5, nsp12, nsp13, and nsp14. All the protein crystal structures and 3D structures of the small molecules (16 gallic acid derivatives and 3 control drugs) were retrieved from the Protein database (PDB) and PubChem server respectively. The compounds with lower binding energy than the control drugs were selected and subjected to pharmacokinetics screening using AdmetSAR server. RESULTS: 4-O-(6-galloylglucoside) gave binding energy values of - 8.4, - 6.8, - 8.9, - 9.1, and - 7.5 kcal/mol against Mpro, nsp3, nsp12, nsp13, and nsp15 respectively. Based on the ADMET profile, 4-O-(6-galloylglucoside) was found to be metabolized by the liver and has a very high plasma protein binding. CONCLUSION: The result of this study revealed that 4-O-(6-galloylglucoside) could be a promising inhibitor against these SAR-Cov-2 proteins. However, there is still a need for further molecular dynamic simulation, in vivo and in vitro studies to support these findings.

Laboratory monitoring of hematological and hepatic parameters in ambulatory patients receiving alpha-methyldopa in a Nigerian tertiary care setting.

The objective of the study is to assess the frequency and comprehensiveness of laboratory monitoring of hematological and hepatic parameters in ambulatory Nigerian hypertensive patients on methyldopa therapy. A retrospective cross sectional study was conducted between 1(st) February and 31(st) March 2007 at the Medical Outpatient Clinic of a 900-bed premier teaching hospital located in Ibadan, Nigeria. 260 case notes of hypertensive patients, out of the 1178 case notes of patients who had been prescribed at least 250 mg of methyldopa for at least 2 months, were reviewed. 22.1% of the hypertensive patients were on methyldopa alone or in combination with other anti-hypertensives for a mean period of 26.8+/-2.3 months (Range: 2-36 months). Overall, red cell count was prescribed and conducted in only 15.4% (40) of cohort. Only 4.2% (11) of patients had follow-up red cell count done after one month of methyldopa therapy; 9 out of these patients had marked reduction of red blood cells. Only 2.3% of cohort had baseline Liver Function Test (LFT) before start of methyldopa therapy and Alanine Transaminases and Aspartate transaminases levels were elevated in all patients. No patient had subsequent LFT prescribed and conducted particularly within 6-12 weeks of use of methyldopa. Direct Anti-Globulin Test was neither prescribed nor conducted in any of the cohort before and after commencement of methyldopa therapy. In conclusion, laboratory monitoring of ambulatory hypertensive patients on methyldopa therapy particularly for possible hematological and hepatic toxicities is less than optimal. The consequent therapeutic benefit of continuing considerable prescription and use of methyldopa in Nigeria is less likely to be realized without proper monitoring to preclude possible methyldopa-use related harms.