Publications by authors named "Sherif Aly El-Kafrawy"

8 Publications

  • Page 1 of 1

Structure-Based Identification of Natural Products as SARS-CoV-2 M Antagonist from Using Computational Approaches.

Viruses 2021 Feb 15;13(2). Epub 2021 Feb 15.

Centre for Bioinformatics, Computational and Systems Biology, Pathfinder Research and Training Foundation, Greater Noida 201308, India.

Coronavirus disease-19 (COVID-19) pandemic, caused by the novel SARS-CoV-2 virus, continues to be a global threat. The number of cases and deaths will remain escalating due to the lack of effective therapeutic agents. Several studies have established the importance of the viral main protease (M) in the replication of SARS-CoV-2 which makes it an attractive target for antiviral drug development, including pharmaceutical repurposing and other medicinal chemistry approaches. Identification of natural products with considerable inhibitory potential against SARS-CoV-2 could be beneficial as a rapid and potent alternative with drug-likeness by comparison to de novo antiviral drug discovery approaches. Thereof, we carried out the structure-based screening of natural products from , commonly used to prevent cold and other microbial respiratory infections, targeting SARS-CoV-2 M. Four natural products namely, Echinacoside, Quercetagetin 7-glucoside, Levan N, Inulin from chicory, and 1,3-Dicaffeoylquinic acid, revealed significant docking energy (>-10 kcal/mol) in the SARS-CoV-2 M catalytic pocket via substantial intermolecular contacts formation against co-crystallized ligand (<-4 kcal/mol). Furthermore, the docked poses of SARS-CoV-2 M with selected natural products showed conformational stability through molecular dynamics. Exploring the end-point net binding energy exhibited substantial contribution of Coulomb and van der Waals interactions to the stability of respective docked conformations. These results advocated the natural products from for further experimental studies with an elevated probability to discover the potent SARS-CoV-2 M antagonist with higher affinity and drug-likeness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/v13020305DOI Listing
February 2021

prediction and experimental validation of siRNAs targeting ORF1ab of MERS-CoV in Vero cell line.

Saudi J Biol Sci 2021 Feb 27;28(2):1348-1355. Epub 2020 Nov 27.

Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Post Box No-80216, Jeddah 21589, Saudi Arabia.

The Middle East Respiratory Syndrome Coronavirus is well known to cause respiratory syndrome and this virus was identified and isolated for the first time from Jeddah, Saudi Arabia in 2012 from infected patient. In this report, we have conducted the prediction, designing and evaluation of siRNAs targeting Middle East Respiratory Syndrome Coronavirus orf1ab gene to inhibit the virus replication. By using bioinformatics software, total twenty-one functional, off-target reduced siRNA were selected from four hundred and sixty-two siRNAs based on their greater potency and specificity. We have evaluated only seven siRNAs to analyze their performance and efficacy as antivirals by reverse transfection approach in Vero cells. There was no cytotoxicity of siRNAs at various concentrations was observed in Vero cells. Based on the real-time PCR results, better inhibition of viral replication was observed in the siRNA-1 and 4 as compared to other siRNAs. The results generated from this work provided suitable information about the efficacy of siRNAs which encouraged us to further evaluate the remaining siRNAs to determine their inhibitory effect on the virus replication. We concluded that the insilico prediction and designing resulted in the screening of potential siRNAs with better efficiency, and strength. This can be used to develop oligonucleotide-based antiviral therapeutics against MERS-CoV in the near future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.sjbs.2020.11.066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833792PMC
February 2021

Designing and evaluation of MERS-CoV siRNAs in HEK-293 cell line.

J Infect Public Health 2021 Feb 29;14(2):238-243. Epub 2020 Dec 29.

Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Post Box, No-80216, Jeddah 21589, Saudi Arabia; Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.

Background: The MERS-CoV was identified for the first time from Jeddah, Saudi Arabia in 2012 from a hospitalized patient. This virus has now been spread to 27 countries with a total of 858 deaths and 2494 confirmed cases and has become a serious concern for the human population. Camels are well known for the transmission of the virus to the human population.

Methods: In this report, we have discussed the designing, prediction, and evaluation of potential siRNAs against the orf1ab gene of MERS-CoV. The online software was used to predict and design the siRNAs and finally, total twenty-one siRNA were filtered out from four hundred and sixty-two sIRNAs as per their scoring and specificity criteria. We have used only ten siRNAs to evaluate their cytotoxicity and efficacy by reverse transfection approach in HEK-293-T cell lines.

Results: Based on the results and data generated; no cytotoxicity was observed for any siRNAs at various concentrations in HEK-293-T cells. The ct value of real-time PCR showed the inhibition of viral replication in siRNA-1, 2, 4, 6, and 9. The data generated provided the preliminary information and encouraged us to evaluate the remaining siRNAs separately as well as in combination to analyses the replication of MERS-CoV inhibition in other cell lines.

Conclusion: Based on the results obtained; it is concluded that the prediction of siRNAs using online software resulted in the filtration of potential siRNAs with high accuracy and strength. This technology can be used to design and develop antiviral therapy not only for MERS-CoV but also against other viruses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jiph.2020.12.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771261PMC
February 2021

In silico Prediction and Designing of Potential siRNAs to be Used as Antivirals Against SARS-CoV-2.

Curr Pharm Des 2021 Jan 11. Epub 2021 Jan 11.

Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah,. Saudi Arabia.

Background: The unusual pneumonia outbreak that originated in the city of Wuhan, China in December 2019 was found to be caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or COVID-19.

Methods: In this work, we have performed an in silico design and prediction of potential siRNAs based on genetic diversity and recombination patterns, targeting various genes of SARS-CoV-2 for antiviral therapeutics. We performed extensive sequence analysis to analyze the genetic diversity and phylogenetic relationships, and to identify the possible source of virus reservoirs and recombination patterns, and the evolution of the virus as well as we designed the siRNAs which can be used as antivirals against SARS-CoV-2.

Results: The sequence analysis and phylogenetic relationships indicated high sequence identity and closed clusters with many types of coronavirus. In our analysis, the full-genome of SARS-CoV-2 showed the highest sequence (nucleotide) identity with SARS-bat-ZC45 (87.7%). The overall sequence identity ranged from 74.3% to 87.7% with selected SARS viruses. The recombination analysis indicated the bat SARS virus is a potential recombinant and serves as a major and minor parent. We have predicted 442 siRNAs and finally selected only 19 functional, and potential siRNAs.

Conclusions: The siRNAs were predicted and selected based on their greater potency and specificity. The predicted siRNAs need to be validated experimentally for their effective binding and antiviral activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1381612827999210111194101DOI Listing
January 2021

Seroprevalence of Dromedary Camel HEV in Domestic and Imported Camels from Saudi Arabia.

Viruses 2020 05 18;12(5). Epub 2020 May 18.

Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia.

Hepatitis E Virus (HEV) imposes a major health concern in areas with very poor sanitation in Africa and Asia. The pathogen is transmitted mainly through ingesting contaminated water or food, coming into contact with affected people, and blood transfusions. Very few reports including old reports are available on the prevalence of HEV in Saudi Arabia in humans and no reports exist on HEV prevalence in camels. Dromedary camel trade and farming are increasing in Saudi Arabia with importation occurring unidirectionally from Africa to Saudi Arabia. DcHEV transmission to humans has been reported in one case from the United Arab Emeritus (UAE). This instigated us to perform this investigation of the seroprevalence of HEV in imported and domestic camels in Saudi Arabia. Serum samples were collected from imported and domestic camels. DcHEV-Abs were detected in collected sera using ELISA. The prevalence of DcHEV in the collected samples was 23.1% with slightly lower prevalence in imported camels than domestic camels (22.4% vs. 25.4%, value = 0.3). Gender was significantly associated with the prevalence of HEV in the collected camels ( value = 0.015) where males (31.6%) were more infected than females (13.4%). This study is the first study to investigate the prevalence of HEV in dromedary camels from Saudi Arabia. The high seroprevalence of DcHEV in dromedaries might indicate their role as a zoonotic reservoir for viral infection to humans. Future HEV seroprevalence studies in humans are needed to investigate the role of DcHEV in the Saudi human population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/v12050553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290434PMC
May 2020

IgY antibodies for the immunoprophylaxis and therapy of respiratory infections.

Hum Vaccin Immunother 2019 19;15(1):264-275. Epub 2018 Sep 19.

c Special Infectious Agents Unit, King Fahd Medical Research Center , King Abdulaziz University , Jeddah , Saudi Arabia.

Emergence of drug resistance among the causative organisms for respiratory tract infections represents a critical challenge to the global health care community. Further, although vaccination can prevent disease, vaccine development is impeded by several factors. Therefore, novel approaches to treat and manage respiratory infections are urgently needed. Passive immunization represents a possible alternative to meet this need. Immunoglobulin Y antibodies (IgYs) from the yolk of chicken eggs have previously been used against bacterial and viral infections in human and animals. Their advantages include lack of reaction with mammalian Fc receptors, low production cost, and ease of extraction. Compared to mammalian IgGs, they have higher target specificity and greater binding avidity. They also possess remarkable pathogen-neutralizing activity in the respiratory tract and lungs. In this review, we provide an overview of avian IgYs and describe their potential therapeutic applications for the prevention and treatment of respiratory infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21645515.2018.1514224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363154PMC
February 2020

Analysis of Hepatitis B virus (HBV) mutations in patients from Western Saudi Arabia with chronic disease.

J Infect Dev Ctries 2018 Jul 31;12(7):557-567. Epub 2018 Jul 31.

King Abdulaziz University, Jeddah, Saudi Arabia.

Introduction: Extensive research has provided a link between HBV variants and the clinical complications of liver diseases. This study was performed to further investigate the relationship between HBV variants in preS, S and BCP/PC regions and disease progression in chronic hepatitis B (CHB) cases in Jeddah, Saudi Arabia.

Methodology: 182 CHB patients were recruited for this study. HBV DNA was amplified by PCR in the PreS, S, and BCP/PC regions. Sequences were generated from 31 and 26 treated cases in PreS and S regions respectively and from 72 cases in the BCP/PC region.

Results: The majority of cases (86.7%) were genotype D. Mutations at preS1-A2922C, X-A1624C and PC-G1887A were detected only in cases with either a high fibrosis score or hepatocellular carcinoma (HCC), while mutations at positions PC-C1982A, PC-G1951T, X-C1628T and X-A1630G were detected more frequently in HCC cases, without reaching statistical significance. Seven deletions were detected in the PreS-region. No deletions were detected in the CCAAT box. The accumulation of mutations per sample in the preS1-2 and S regions were associated with elevated ALT (p < 0.001, 0.001 and 0.001; respectively) and increased fibrosis (p = 0.018, 0.02 and 0.013; respectively). The accumulation of mutations per sample in the BCP/PC region is associated with high viral load. Occult hepatitis B infection (OBI) was identified in 5 samples.

Conclusion: Our results add to the knowledge about HBV genotype-D variants. The accumulation of mutations per sample and OBI seem to play a role in the progression of HBV infection. G1896A was associated with the HBeAg negativity. The preS deletions did not play a role in liver disease progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3855/jidc.9534DOI Listing
July 2018

Design and Delivery of Therapeutic siRNAs: Application to MERS-Coronavirus.

Curr Pharm Des 2018 ;24(1):62-77

Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.

Background: The MERS-CoV is a novel human coronavirus causing respiratory syndrome since April 2012. The replication of MERS-CoV is mediated by ORF 1ab and viral gene activity can be modulated by RNAi approach. The inhibition of virus replication has been documented in cell culture against multiple viruses by RNAi approach. Currently, very few siRNA against MERS-CoV have been computationally designed and published.

Methods: In this review, we have discussed the computational designing and delivery of potential siRNAs. Potential siRNA can be designed to silence a desired gene by considering many factors like target site, specificity, length and nucleotide content of siRNA, removal of potential off-target sites, toxicity and immunogenic responses. The efficient delivery of siRNAs into targeted cells faces many challenges like enzymatic degradation and quick clearance through renal system. The siRNA can be delivered using transfection, electroporation and viral gene transfer. Currently, siRNAs delivery has been improved by using advanced nanotechnology like lipid nanoparticles, inorganic nanoparticles and polymeric nanoparticles.

Conclusion: The efficacy of siRNA-based therapeutics has been used not only against many viral diseases but also against non-viral diseases, cancer, dominant genetic disorders, and autoimmune disease. This innovative technology has attracted researchers, academia and pharmaceuticals industries towards designing and development of highly effective and targeted disease therapy. By using this technology, effective and potential siRNAs can be designed, delivered and their efficacy with toxic effects and immunogenic responses can be tested against MERS-CoV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1381612823666171109112307DOI Listing
September 2019