Computational Screening of Repurposed Drugs Targeting Sars-Cov-2 Main Protease By Molecular Docking

Background: COVID-19 (Coronavirus disease 2019) is caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which poses significant global health and economic crisis that urges effective treatment. Methods: A total of 11 molecules (baricitinib, danoprevir, dexamethasone, hydroxychloroquine, ivermectin, lopinavir, methylprednisolone, remdesivir, ritonavir and saridegib, ascorbic acid, and cepharanthine) were selected for molecular docking studies using AutoDock VINA to study their antiviral activities via targeting SARS-CoV’s main protease (Mpro), a cysteine protease that mediates the maturation cleavage of polyproteins during virus replication. Results: Three drugs showed stronger binding affinity toward Mpro than N3 (active Mpro inhibitor as control): danoprevir (–7.7 kcal/mol), remdesivir (–8.1 kcal/mol), and saridegib (–7.8 kcal/mol). Two primary conventional hydrogen bonds were identified in the danoprevir-Mpro complex at GlyA:143 and GlnA:189, whereas the residue GluA:166 formed a carbon–hydrogen bond. Seven main conventional hydrogen bonds were identified in the remdesivir at AsnA:142, SerA:144, CysA:145, HisA:163, GluA:166, and GlnA:189, whereas two carbon–hydrogen bonds were formed by the residues HisA:41 and MetA:165. Cepharanthine showed a better binding affinity toward Mpro (–7.9 kcal/mol) than ascorbic acid (–5.4 kcal/mol). Four carbon–hydrogen bonds were formed in the cepharanthine-Mpro complex at HisA:164, ProA;168, GlnA;189, and ThrA:190. Conclusion: The findings of this study propose that these drugs are potentially inhibiting the SAR-CoV-2 virus by targeting the Mpro protein

Awareness, knowledge and attitude towards epilepsy in Malaysia: A perspective of undergraduates in a private university

Background: Stigma of epilepsy continues to negatively impact on the quality of life of people with epilepsy. It is important for undergraduates to be aware and possess accurate knowledge towards epilepsy. This study aimed to assess the awareness, knowledge and attitude towards epilepsy among the undergraduates in a private university. Methods:  A cross-sectional study was conducted using a self-administered questionnaire in Taylor’s University, Malaysia. A validated questionnaire was administered, consisting of 17 items on awareness, knowledge and attitude towards epilepsy. Results:  A total of 371 undergraduates participated with a response rate of 94%. The respondents comprised of majority females (62.0%), Chinese ethnicity (74.7%) and Malaysian (88.4%). They possessed a low level of awareness (64.7%), with 71.7% of them having heard or read about epilepsy but only 16.2% had attended epilepsy-related seminars or lectures. Approximately two-thirds (64.2%) demonstrated a high level of knowledge as the majority denied that epilepsy was contagious and caused by evil spirits. Most respondents demonstrated a positive attitude (74.7%) by accepting the involvement of people with epilepsy in sports, marriage and socialization. Awareness and knowledge towards epilepsy were significantly associated with both the undergraduates’ faculty and year of study (p < 0.05). Attitude towards epilepsy was significantly associated with only the faculty (p < 0.05). Conclusion: Although the level of knowledge and attitude were generally quite satisfactory, the awareness was still low among  undergraduates. This study highlighted the need for formal education and awareness campaigns in the university to improve their  awareness, knowledge and attitude toward epilepsy.   French  title: Connaissances, attitudes et pratiques envers l'épilepsie chez des étudiants de premier cycle dans une université privée en Malaisie Introduction:  La stigmatisation de l'épilepsie continue d'avoir un impact négatif sur la qualité de vie des personnes épileptiques. Il est important que les étudiants de premier cycle soient conscients et possèdent des connaissances précises sur l'épilepsie. Cette étude visait à évaluer la sensibilisation, les connaissances et l'attitude envers l'épilepsie parmi les étudiants de premier cycle d'une université privée. Méthodes:  Une étude transversale a été menée à l’aide d’un questionnaire auto-administré à l’Université de Taylor, en Malaisie. Un questionnaire validé a été administré, composé de 17 items sur la sensibilisation, les connaissances et l'attitude envers l'épilepsie. Résultats_  Un total de 371 étudiants de premier cycle ont participé à l’étude avec un taux de réponse de 94%. Les répondants étaient majoritairement des femmes (62,0%), d'origine chinoise (74,7%) et malaisienne (88,4%). Ils possédaient un faible niveau de sensibilisation (64,7%), 71,7% d'entre eux ayant entendu ou lu sur l'épilepsie mais seulement 16,2% avaient assisté à des séminaires ou à des conférences sur l'épilepsie. Environ les deux tiers (64,2%) ont démontré un niveau élevé de connaissances, la majorité niant que l'épilepsie était contagieuse et causée par de mauvais esprits. La plupart des répondants ont fait preuve d'une attitude positive (74,7%) en acceptant l'implication des personnes épileptiques dans le sport, le mariage et la socialisation. La sensibilisation et la connaissance de l’épilepsie étaient associées de manière significative à la fois à la faculté des étudiants de premier cycle et à l’année d’études (p <0,05). L'attitude à l'égard de l'épilepsie était significativement associée à la faculté uniquement (p <0,05). Conclusion: Bien que le niveau de connaissances et l'attitude soient généralement assez satisfaisants, la sensibilisation est encore faible parmi les étudiants de premier cycle. Cette étude a souligné la nécessité d'une éducation formelle et de campagnes de sensibilisation à l'université pour améliorer leur prise de conscience, leurs connaissances et leur attitude face à l'épilepsie

THE POTENTIAL ROLE OF GENUS TINOSPORA IN WOUND HEALING: A REVIEW

Genus Tinospora has been used in traditional medicine throughout various parts of Asia, particularly in India, China, Thailand, Malaysia and Cambodia. Its ethnomedicinal uses include treatment for fever, cold, oral ulcer, headaches, diarrhoea, diabetes, digestive disorder and rheumatoid arthritis. Some of its ethnomedicinal uses have been justified via scientific studies, include antidiabetic, antioxidant, anti-inflammatory and antimicrobial effects. Recently, several studies have been initiated to investigate the role of Tinospora species in wound healing. This comprehensive review used updated information obtained from systematic literature search using PubMed, Scopus, Science Direct and Google Scholar, to assess the wound healing properties of eleven major Tinospora species namely, T. cordifolia, T. crispa, T. sagittata, T. sinensis, T. bakis, T. craveniana, T. tuberculata, T. capillipes, T. rumphii, T. smilacina, and T. baenzigeri. The information obtained revealed that only T. cordifolia and T. crispa have been reported on its wound-healing abilities. Studies demonstrated that T. cordifolia is associated with early re-epithelisation, enhanced tensile strength, increased granulation tissues and increased collagen contents. Whereas T. crispa is reported with wound healing activity through the elevated antioxidant enzymes and inflammation phase. Nevertheless, there is limited evidence on phytochemical constituents from plant extracts that contribute to the wound healing process and their underlying mechanisms. This review deduced the potential gaps for future research aiming to study the genus Tinospora as a potential wound healing agent

Pathogenesis of Epilepsy: Challenges in Animal Models

Epilepsy is one of the most common chronic disorders affecting individuals of all ages. A greater understanding of pathogenesis in epilepsy will likely provide the basis fundamental for development of new antiepileptic therapies that aim to prevent the epileptogenesis process or modify the progression of epilepsy in addition to treatment of epilepsy symptomatically. Therefore, several investigations have embarked on advancing knowledge of the mechanism underlying epileptogenesis, understanding in mechanism of pharmacoresistance and discovering antiepileptogenic or disease-modifying therapy. Animal models play a crucial and significant role in providing additional insight into mechanism of epileptogenesis. With the help of these models, epileptogenesis process has been demonstrated to be involved in various molecular and biological pathways or processes. Hence, this article will discuss the known and postulated mechanisms of epileptogenesis and challenges in using the animal models

Medication-handling challenges among visually impaired population

Objective: Visually impaired individuals are particularly at higher risk for experiencing a medication error. The aim of this study is to identify the problems encountered by the visually impaired population when handling their medication. Methods: A cross-sectional survey was conducted using an interviewer-guided questionnaire with 100 visually impaired individuals. The questionnaire comprised a series of questions in medication management. Results: All of the respondents perceived that self-administration of medication was a challenging task. A total of 89% of respondents were unable to read the prescription labels, 75% of respondents did not know the expiry date of their own medication, and 58% of respondents did not know the name of the medication. With regard to storage of medication, 72% of respondents did not practice appropriate methods to store their medication, and 80% of respondents kept the unused medication. All of the respondents disposed leftover medication through household rubbish. A total of 64% of respondents never practice medication review. Most (96%) of them did not tell health-care providers when they faced difficulties in handling their medication. Conclusion: Most of the visually impaired individuals did not receive appropriate assistance regarding medicine use and having low awareness in medication management. This can lead to increased risk of medication errors or mismanagement among visually impaired population. Hence, effective strategies, especially in pharmaceutical care services, should be structured to assist this special population in medication handling

Pharmacogenomics of Cancer Pain Treatment Outcomes in Asian Populations: A Review

In advanced cancer, pain is a poor prognostic factor, significantly impacting patients’ quality of life. It has been shown that up to 30% of cancer patients in Southeast Asian countries may receive inadequate analgesia from opioid therapy. This significant under-management of cancer pain is largely due to the inter-individual variability in opioid dosage and relative efficacy of available opioids, leading to unpredictable clinical responses to opioid treatment. Single nucleotide polymorphisms (SNPs) cause the variability in opioid treatment outcomes, yet their association in Asian populations remains unclear. Therefore, this review aimed to evaluate the association of SNPs with variability in opioid treatment responses in Asian populations. A literature search was conducted in Medline and Embase databases and included primary studies investigating the association of SNPs in opioid treatment outcomes, namely pharmacokinetics, opioid dose requirements, and pain control among Asian cancer patients. The results show that CYP2D6*10 has the most clinical relevance in tramadol treatment. Other SNPs such as rs7439366 (UGT2B7), rs1641025 (ABAT) and rs1718125 (P2RX7) though significant have limited pharmacogenetic implications due to insufficient evidence. OPRM1 rs1799971, COMT rs4680 and ABCB1 (rs1045642, rs1128503, and rs2032582) need to be further explored in future for relevance in Asian populations

Rare Compound Heterozygous Frameshift Mutations in ALMS1 Gene Identified Through Exome Sequencing in a Taiwanese Patient With Alström Syndrome

Alström syndrome (AS) is a rare autosomal recessive disorder that shares clinical features with other ciliopathy-related diseases. Genetic mutation analysis is often required in making differential diagnosis but usually costly in time and effort using conventional Sanger sequencing. Herein we describe a Taiwanese patient presenting cone-rod dystrophy and early-onset obesity that progressed to diabetes mellitus with marked insulin resistance during adolescence. Whole exome sequencing of the patient's genomic DNA identified a novel frameshift mutation in exons 15 (c.10290_10291delTA, p.Lys3431Serfs*10) and a rare mutation in 16 (c.10823_10824delAG, p.Arg3609Alafs*6) of ALMS1 gene. The compound heterozygous mutations were predicted to render truncated proteins. This report highlighted the clinical utility of exome sequencing and extended the knowledge of mutation spectrum in AS patients