ABSTRACT
Background SARS-CoV-2 emerged in late 2019, causes COVID-19. Patients treated with Zyesami were found to be 3-fold decrease in respiratory failure and improvement in clinical outcome. It was reported that Zyesami inhibits RNA replication of SARS-CoV-2, including several non-structural proteins that essential in viral RNA replication. SARS-CoV-2 is a distinctive virus that required nsp10 and nsp16 for its methyltransferases activity which is crucial for RNA stability and protein synthesis. Objective We aimed the in silico determination of inhibitory consequences of Zyesami on the SARS-CoV-2 nsp10/nsp16 complex. Targeting SARS-CoV-2 nsp10/ nsp16 protein complex may be used for the development of drug against the COVID-19. Methods I-TASSER was used for secondary structure prediction of Zyesami. CABS-dock was used for modelling of Zyesami with SARS-CoV-2 nsp16 interaction. The docked complex was visualized using PyMol. The quality of the docking model was checked by using ProQdock. Results The 3D structure of SARS-CoV 2, nsp10/nsp16 showed that essential interactions exist between nsp10 and nsp16. Significant contact areas of Zyesami exist across amino acid residues of nsp10; Asn40-Thr47, Val57-Pro59, Gly69-Ser72, Cys77-Pro84, Lys93-Tyr96. In addition, polar contacts between nsp16 and Zyesami are Asn299-Ser440, Val297-Asn443, Gly149-Tyr437, Gln159-Lys430, Asn178-Arg429, Ser146-Arg429, Ser146-Arg429, Lys147-Arg429, Asr221-Thr422, Lys183-Asp423, Lys183-Asp423, and Gln219-Asp423 the residues are shown of nsp16 and Zyesami respectively. Conclusion The structural bioinformatics analyses have indicated the potential binding specificity of Zyesami and nsp16. Data predict how the initial binding of Zyesami with nsp10 and nsp16 may occur. Moreover, this binding could significantly inhibit the 2 -O-MTase activity of the SARS-CoV nsp10/16 complex.
ABSTRACT
Numerous measures have been taken to slow the Coronavirus disease (COVID-19) rapid spread. Such population control techniques may have a substantial impact on people's attitudes, knowledge, and perception of COVID-19. This web-based cross-sectional survey aimed to assess Knowledge, Attitude, and Practices (KAP) towards COVID-19 among Hadhramout University Medical Students in Yemen from 15 June to 26 June 2020. This survey was performed using social media via the Google Platform among 422 Hadhramout University Medical students. After consenting, participants completed an online survey assessing sociodemographic data, 21 knowledge items, 15 attitudes items, and 5 perception items towards COVID-19. Of the total 422 participants, 389 (92.18%) were surveyed online, and 256 (65.8%) were females, and 133 (34.2%) were males aged 19-24 years (88.7%), studying medicine (58.9%), and living in urban areas (80.7%). The survey revealed that 64.0% of participants had good knowledge about the disease and 52.7% had positive attitudes towards protective measures against the virus. The majority of participants (98.2%) thought that the virus was transmitted through nasal droplets, and 59.6% agreed that the disease is dangerous. The majority of participants agreed that fever (99.2%), dry cough (97.9%), and difficulty breathing (99.5%) are the most common symptoms of the disease. The survey also showed high knowledge levels about preventive measures against the virus spreading, such as regular proper hand hygiene (99.7%), maintaining an appropriate distance (99.2%), avoiding touching eyes and nose (98.7%), and wearing facemasks in public places (97.4%). Moreover, 69.7% of participants agreed to be isolated at home if they got an infected person, 64.3% implemented washing hands with soap and water, 41.9% agreed to be separated at the hospital until they proved free from the disease, 46.0% agreed to inform the health authorities if they had any symptoms associated with the disease. By using sample T-test and analysis of variance (ANOVA), mean knowledge score about COVID-19 was significantly higher in males than in females (p = 0.029). Additionally, medicine students had significantly higher mean knowledge score than students of medical laboratory (p < 0.001) and nursing (p = 0.008). In general, our research revealed that participants had favorable opinions regarding the disease's preventative measures and a good awareness of it. However, more educational initiatives and campaigns that take into account KAP modifying elements are needed.
ABSTRACT
Dexamethasone is a synthetic glucocorticoid medication vastly used to treat abnormal immune responses and inflammation. Although the medication is well-established in the medical community, the prolonged treatment with high dosages of dexamethasone may lead to severe adverse effects through mechanisms that are not yet well-known. Lipids are a large class of hydrophobic molecules involved in energy storage, signaling, modulation of gene expression, and membranes. Hence, untargeted lipidomics may help unravel the biochemical alterations following prolonged treatment with high dosages of dexamethasone. We performed comprehensive lipidomic analyses of brain, heart, kidney, liver, and muscle samples obtained from rats that were treated with intramuscular injections of dexamethasone for 14 weeks compared to healthy controls. The employed methodology and statistical analysis showed that phosphatidic acids, glycerophospholipids, plasmalogens, and fatty acids are deeply affected by prolonged use of the medication. Brain tissue was only mildly affected, but skeletal muscle showed a strong accumulation of lipids that may be correlated with alterations in the energy metabolism, myopathy, and oxidative processes. This work provides new insights into the mechanisms of action and adverse effects for one of the most commonly prescribed class of drugs in the world.