ARTICLE | doi:10.20944/preprints202002.0308.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: SARS-CoV-2; COVID-19; 3CL protease; molecular docking; molecular dynamics and simulations
Online: 23 February 2020 (02:17:46 CET)
The SARS-CoV-2 was confirmed to cause the regional outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China. The 3C-like protease (3CLpro), an essential enzyme for viral replication, is a valid target to compacts SARS-CoV and MERS-CoV. In this research, an integrated library consisting of 1000 compounds from Asinex Focused Covalent (AFCL) library and 16 FDA-approved protease inhibitors were screened against SARS-CoV-2 3CLpro. Top compounds with significant docking scores and making stable interactions with catalytic dyad residues were obtained. The screening results in identification of compound 621 from AFCL library as well as Paritaprevir and Simeprevir from FDA-approved protease inhibitors as potential inhibitors of SARS-CoV-2 3CLpro. The mechanism and dynamic stability of binding between the identified compounds and SARS-CoV-2 3CLpro were characterized using 50 nanoseconds (ns) molecular dynamic (MD) simulation approach. The identified compounds are potential inhibitors worthy of further development as SARS-CoV-2 3CLpro inhibitors/drugs. Importantly, the identified FDA-approved therapeutics could be ready for clinical trials to treat infected patients and help to curb the COVID-19.
REVIEW | doi:10.20944/preprints202008.0308.v1
Subject: Biology, Other Keywords: Hereditary HL; genetics of syndromic and non-syndromic HL; methods for pathogenic locus/gene identification
Online: 14 August 2020 (04:45:23 CEST)
Hearing impairment is an immensely diagnosed genetic cause, 5% of the total world population effects with different kind of congenital hearing loss (HL). In third-world countries or countries where consanguineous marriages are more common the frequency rate of genetic disorders are at its zenith. Approximately, the incidence of hearing afflictions is ostensibly 7-8:1000 individuals whereas it is estimated that about 466 million peoples suffer with significant HL, and of theses deaf cases 34 million are children’s up to March, 2020. Several genes and colossal numbers of pathogenic variants cause hearing impairment, which aided in next-generation with recessive, dominant or X-linked inheritance traits. This review highlights on syndromic and non-syndromic HL (SHL and NSHL), and categorized as conductive, sensorineural and mixed HL, which having autosomal dominant and recessive, and X-linked or mitochondrial mode of inheritance. Many hundred genes involved in HL are reported, and their mutation spectrum becomes very wide. Mapping of pathogenic genes in consanguinity family is facilitated to understand the disease history. Review presents the bases of HL and also focused on various genetic factors that cause deafness like the basics of genetic inheritance, and classic and well-characterized inherited factors of it. It also overviews the application of linkage analysis, SNPs genotyping and whole exome sequencing methods, in mapping and identification of new locus, causative genes and their variants in families inherited with HL. Conclusively, this review supports researchers in understanding the location of chromosome, the causative genes and specific locus which causing deafness in humans.
ARTICLE | doi:10.20944/preprints202007.0510.v1
Subject: Engineering, Civil Engineering Keywords: Aerated concrete; ultimate load; finite element analysis and rice husk ash
Online: 22 July 2020 (09:56:53 CEST)
Aerated concrete, which is manufactured from binding material, sand, foaming agent and water, is currently being utilized in the construction industry because of its lightweight and durability. The binding material, cement, along with other materials used in the concrete produces huge carbon footprints during its fabrication. The utilization of natural aggregates name as coarse aggregates depletes the natural resources of the country. Therefore, huge amounts of agricultural wastes have led scholars to investigate the effectiveness of replacing conventional materials used in concrete with agricultural wastes. In the current study, rice husk ash (RHA) was used as supplementary cementing material, thereby reducing the amount of cement used in aerated concrete (AC) mixture will reduce carbon footprints. The experimental and numerical analysis were conducted to investigate structural behavior of reinforced RAC- B beams subjected to flexural load. Parametric study on structural performance of RAC- B beam under flexure were conducted using finite element analysis (FEA). From the experiment and FEA. Results from the parametric study showed that RAC-10%RHA-B with higher depth structurally performed better compared to RAC-B under flexure with greater load carrying capacity, lesser maximum deflection, and less cracks developing in the tension area.
REVIEW | doi:10.20944/preprints201907.0277.v1
Subject: Biology, Animal Sciences & Zoology Keywords: thalassemia; iron overload; chelation therapy; gene therapy; blood transfusion
Online: 25 July 2019 (01:20:41 CEST)
Thalassemia is genetic blood disease cause by absence or decrease of one or more of the globin chain synthesis. Beta thalassemia is characterized by one or more mutations in beta globin gene. Absence or reduced amount the of beta globin chains cause ineffective erythropoiesis which leads to anemia. Beta thalassemia has been further divided into three main forms: Thalassemia minor/silent carrier, major and intermedia. More severe form is thalassemia major in which patients depend upon blood transfusion for survival and high level of iron occur as a consequence of consistent blood transfusion. Over loaded iron invokes the synthesis of reactive oxygen species that are toxic in redundancy and triggering the impairment to vascular, endocrine and hepatic system. Thalassemia can be diagnosed and detected through various laboratory tests such as blood smear, prenatal testing (genetic testing of amniotic fluid), DNA analysis (genetic testing) and complete blood count. Treatment of thalassemia intermedia is symptomatic but it can also be managed by splenectomy and folic supplementation. While thalassemia major can be treated by transplantation of bone marrow, regular transfusion of blood and iron chelation treatment, stimulation of fetal hemoglobin production, hematopoietic stem cell transplantation and gene therapy.
ARTICLE | doi:10.20944/preprints202105.0541.v1
Subject: Keywords: Artificial intelligence; Accounting systems integration; Accounting systems accuracy; Financial statements; Aqaba Special Economic Zone
Online: 24 May 2021 (08:47:20 CEST)
The study aims to examine the effects of artificial intelligence (AI) on the consistency and analysis of financial statements in hotels in ASEZA, Jordan. This research is an exploratory, empirical study, which uses the methodology of data collection and interpretation to draw conclusions. The researchers used the arithmetic mean, standard deviation, T-test and ANOVA test to calculate the degree of significance of the study questions. The findings of a basic linear regression study of the impact of AI implemented in Jordanian hotels on the integration of accounting information systems and the association between AI and the integration of accounting information systems (R = 59.6%) also indicate that the fixed limit value amounted to (2.060) and the value of (Beta) for T-test
REVIEW | doi:10.20944/preprints202002.0358.v3
Subject: Life Sciences, Virology Keywords: Infectious diseases; Coronavirus; SARS-CoV-2; COVID-19; Pneumonia; China
Online: 28 February 2020 (13:21:43 CET)
The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) linked with coronavirus disease 2019 (COVID-19) poses a serious threat to public health worldwide. Firstly, the SARS-CoV-2 was reported in Wuhan, Hubei Province, China in December 2019. Initially, the major proportion of virus-infected cases (i.e. about 99%) was reported in China and now it is being reported in other counties as well. Humans begin to be infected within their communities and transmittance of the viral epidemic increased rapidly due to lack of understanding of its transmission routes and precautionary measures. The existence of SARS-CoV-2 in China threatened the population greatly due to the high incidence of fatal respiratory infections. Current investigations speculated that this virus transferred into a human from viral-infected bats. However, the process of interspecies viral transmission is an important scientific question to be addressed. Due to the continuous increase in the patients infected with COVID-19 associated pneumonia, the World Health Organization (WHO) has included this viral epidemic to the priority list of diseases. Therefore, accelerated research developments are required to control the spread of this outbreak, as it is declared as a public health emergency by WHO especially in the absence of efficacious drugs and vaccines. Our review encompasses the recent status of disease severity in China, a particular replication mechanism of SARS-CoV-2 and potential risks and precautionary measures required to avoid contact with this fatal viral infection.