Mohamed Ali | King Saud University (original) (raw)
Books by Mohamed Ali
Several infectious diseases, such as polio, measles, diphtheria, rubella, mumps and tetanus can b... more Several infectious diseases, such as polio, measles, diphtheria, rubella, mumps and tetanus can be controlled and, in many cases, be eradicated with current vaccines.
Lower respiratory tract infections due to human respiratory syncytial viruses (HRSV) continue to ... more Lower respiratory tract infections due to human respiratory syncytial viruses (HRSV) continue to threat human beings. The virus causes seasonal epidemics and infects humans of different age groups. Neonates and immunocompromised individuals are more prone to severe HRSV infection that may require hospitalization and in many cases lead to death. According to worldwide estimations, millions of HRSV infection were reported in both developed and developing countries.
For further information see our web site at www.rsc.org vi Preface backbone and side-chain placem... more For further information see our web site at www.rsc.org vi Preface backbone and side-chain placement, NMR also provides dynamic (ensemble) information and crystallography provides a 'snapshot' and is often considered static. Solution approaches, such as limited proteolysis combined with mass spectrometry and small-angle scattering approaches (Chapter 3), also provide dynamic information. In cryo-ET and cryo-electron microscopy (cryo-EM) (Chapter 5), macromolecules are frozen in their native state, allowing for discrete selection of dynamic states to be visualized, albeit at lower resolution. Generally, NMR spectroscopy is utilized for small protein molecules that are flexible, X-ray crystallography for medium-sized proteins and complexes that are compact, whereas very large macromolecular assemblages or membranous protein structures are determined by cryo-EM. The largest issue separating cryo-EM and cryo-ET from crystallography, in addition to size and the limitations of crystal formation, is resolution. Cryo-EM has generally been considered a low-resolution technique, giving reconstructions around 15-30 Å , but with advances in sample handling, instrumentation, image processing and model building, near-atomic resolution structures are now being achieved. For cryo-ET the resolution achieveable is still low. In reality, hybrid approaches, combining NMR, X-ray crystallography and cryo-EM, cryo-ET and solution data, are often adopted, which provides a powerful means of filling gaps which can arise in the structural characterization of large macromolecules. For example, in studies where large viruses cannot be crystallized, subcomponents can be crystallized to obtain high-resolution information, which can then be used to interpret the structure at lower resolution obtained by cryo-EM or cryo-ET. Or atomic structures obtained from homologous viral proteins/virus capsids can be used for 3D homology model building. These approaches permit the pseudo-atomic visualization of interaction interfaces between protein-protein subunits, protein-nucleic acids and protein-lipid in virus capsids and also the visualization of virus capsid-host interactions.
How Pathogenic Viruses Think: Making Sense of Virology, Second Edition, is an independent publica... more How Pathogenic Viruses Think: Making Sense of Virology, Second Edition, is an independent publication and has not been authorized, sponsored, or otherwise approved by the owners of the trademarks or service marks referenced in this product.
For further information see our web site at www.rsc.org vi Preface backbone and side-chain placem... more For further information see our web site at www.rsc.org vi Preface backbone and side-chain placement, NMR also provides dynamic (ensemble) information and crystallography provides a 'snapshot' and is often considered static. Solution approaches, such as limited proteolysis combined with mass spectrometry and small-angle scattering approaches (Chapter 3), also provide dynamic information. In cryo-ET and cryo-electron microscopy (cryo-EM) (Chapter 5), macromolecules are frozen in their native state, allowing for discrete selection of dynamic states to be visualized, albeit at lower resolution. Generally, NMR spectroscopy is utilized for small protein molecules that are flexible, X-ray crystallography for medium-sized proteins and complexes that are compact, whereas very large macromolecular assemblages or membranous protein structures are determined by cryo-EM. The largest issue separating cryo-EM and cryo-ET from crystallography, in addition to size and the limitations of crystal formation, is resolution. Cryo-EM has generally been considered a low-resolution technique, giving reconstructions around 15-30 Å , but with advances in sample handling, instrumentation, image processing and model building, near-atomic resolution structures are now being achieved. For cryo-ET the resolution achieveable is still low. In reality, hybrid approaches, combining NMR, X-ray crystallography and cryo-EM, cryo-ET and solution data, are often adopted, which provides a powerful means of filling gaps which can arise in the structural characterization of large macromolecules. For example, in studies where large viruses cannot be crystallized, subcomponents can be crystallized to obtain high-resolution information, which can then be used to interpret the structure at lower resolution obtained by cryo-EM or cryo-ET. Or atomic structures obtained from homologous viral proteins/virus capsids can be used for 3D homology model building. These approaches permit the pseudo-atomic visualization of interaction interfaces between protein-protein subunits, protein-nucleic acids and protein-lipid in virus capsids and also the visualization of virus capsid-host interactions.
How Pathogenic Viruses Think: Making Sense of Virology, Second Edition, is an independent publica... more How Pathogenic Viruses Think: Making Sense of Virology, Second Edition, is an independent publication and has not been authorized, sponsored, or otherwise approved by the owners of the trademarks or service marks referenced in this product.
Several infectious diseases, such as polio, measles, diphtheria, rubella, mumps and tetanus can b... more Several infectious diseases, such as polio, measles, diphtheria, rubella, mumps and tetanus can be controlled and, in many cases, be eradicated with current vaccines.
Lower respiratory tract infections due to human respiratory syncytial viruses (HRSV) continue to ... more Lower respiratory tract infections due to human respiratory syncytial viruses (HRSV) continue to threat human beings. The virus causes seasonal epidemics and infects humans of different age groups. Neonates and immunocompromised individuals are more prone to severe HRSV infection that may require hospitalization and in many cases lead to death. According to worldwide estimations, millions of HRSV infection were reported in both developed and developing countries.
For further information see our web site at www.rsc.org vi Preface backbone and side-chain placem... more For further information see our web site at www.rsc.org vi Preface backbone and side-chain placement, NMR also provides dynamic (ensemble) information and crystallography provides a 'snapshot' and is often considered static. Solution approaches, such as limited proteolysis combined with mass spectrometry and small-angle scattering approaches (Chapter 3), also provide dynamic information. In cryo-ET and cryo-electron microscopy (cryo-EM) (Chapter 5), macromolecules are frozen in their native state, allowing for discrete selection of dynamic states to be visualized, albeit at lower resolution. Generally, NMR spectroscopy is utilized for small protein molecules that are flexible, X-ray crystallography for medium-sized proteins and complexes that are compact, whereas very large macromolecular assemblages or membranous protein structures are determined by cryo-EM. The largest issue separating cryo-EM and cryo-ET from crystallography, in addition to size and the limitations of crystal formation, is resolution. Cryo-EM has generally been considered a low-resolution technique, giving reconstructions around 15-30 Å , but with advances in sample handling, instrumentation, image processing and model building, near-atomic resolution structures are now being achieved. For cryo-ET the resolution achieveable is still low. In reality, hybrid approaches, combining NMR, X-ray crystallography and cryo-EM, cryo-ET and solution data, are often adopted, which provides a powerful means of filling gaps which can arise in the structural characterization of large macromolecules. For example, in studies where large viruses cannot be crystallized, subcomponents can be crystallized to obtain high-resolution information, which can then be used to interpret the structure at lower resolution obtained by cryo-EM or cryo-ET. Or atomic structures obtained from homologous viral proteins/virus capsids can be used for 3D homology model building. These approaches permit the pseudo-atomic visualization of interaction interfaces between protein-protein subunits, protein-nucleic acids and protein-lipid in virus capsids and also the visualization of virus capsid-host interactions.
How Pathogenic Viruses Think: Making Sense of Virology, Second Edition, is an independent publica... more How Pathogenic Viruses Think: Making Sense of Virology, Second Edition, is an independent publication and has not been authorized, sponsored, or otherwise approved by the owners of the trademarks or service marks referenced in this product.
For further information see our web site at www.rsc.org vi Preface backbone and side-chain placem... more For further information see our web site at www.rsc.org vi Preface backbone and side-chain placement, NMR also provides dynamic (ensemble) information and crystallography provides a 'snapshot' and is often considered static. Solution approaches, such as limited proteolysis combined with mass spectrometry and small-angle scattering approaches (Chapter 3), also provide dynamic information. In cryo-ET and cryo-electron microscopy (cryo-EM) (Chapter 5), macromolecules are frozen in their native state, allowing for discrete selection of dynamic states to be visualized, albeit at lower resolution. Generally, NMR spectroscopy is utilized for small protein molecules that are flexible, X-ray crystallography for medium-sized proteins and complexes that are compact, whereas very large macromolecular assemblages or membranous protein structures are determined by cryo-EM. The largest issue separating cryo-EM and cryo-ET from crystallography, in addition to size and the limitations of crystal formation, is resolution. Cryo-EM has generally been considered a low-resolution technique, giving reconstructions around 15-30 Å , but with advances in sample handling, instrumentation, image processing and model building, near-atomic resolution structures are now being achieved. For cryo-ET the resolution achieveable is still low. In reality, hybrid approaches, combining NMR, X-ray crystallography and cryo-EM, cryo-ET and solution data, are often adopted, which provides a powerful means of filling gaps which can arise in the structural characterization of large macromolecules. For example, in studies where large viruses cannot be crystallized, subcomponents can be crystallized to obtain high-resolution information, which can then be used to interpret the structure at lower resolution obtained by cryo-EM or cryo-ET. Or atomic structures obtained from homologous viral proteins/virus capsids can be used for 3D homology model building. These approaches permit the pseudo-atomic visualization of interaction interfaces between protein-protein subunits, protein-nucleic acids and protein-lipid in virus capsids and also the visualization of virus capsid-host interactions.
How Pathogenic Viruses Think: Making Sense of Virology, Second Edition, is an independent publica... more How Pathogenic Viruses Think: Making Sense of Virology, Second Edition, is an independent publication and has not been authorized, sponsored, or otherwise approved by the owners of the trademarks or service marks referenced in this product.
Acute lower respiratory tract infection is a major health problem that affects more than 15% of t... more Acute lower respiratory tract infection is a major health problem that affects more than 15% of the total population of Saudi Arabia each year. Epidemiological studies conducted over the last three decades have indicated that viruses are responsible for the majority of these infections. The epidemiology of respiratory viruses in Saudi Arabia is proposed to be affected mainly by the presence and mobility of large numbers of foreign workers and the gathering of millions of Muslims in Mecca during the Hajj and Umrah seasons. Knowledge concerning the epidemiology, circulation pattern, and evolutionary kinetics of respiratory viruses in Saudi Arabia are scant, with the available literature being inconsistent. This review summarizes the available data on the epidemiology and evolution of respiratory viruses. The demographic features associated with Middle East respiratory syndrome-related coronavirus infections are specifically analyzed for a better understanding of the epidemiology of this virus. The data support the view that continuous entry and exit of pilgrims and foreign workers with different ethnicities and socioeconomic backgrounds in Saudi Arabia is the most likely vehicle for global dissemination of respiratory viruses and for the emergence of new viruses (or virus variants) capable of greater dissemination.
The development of safe and potent vaccines for human respiratory syncytial virus (HRSV) is still... more The development of safe and potent vaccines for human respiratory syncytial virus (HRSV) is still a
challenge for researchers worldwide. DNA-based immunization is currently a promising approach that has
been used to generate human vaccines for different age groups. In this study, novel HRSV DNA vaccine
candidates were generated and preclinically tested in BALB/c mice. Three different versions of the codonoptimized
HRSV fusion (F) gene were individually cloned into the pPOE vector. The new recombinant
vectors either express full-length (pPOE-F), secretory (pPOE-TF), or M282–90 linked (pPOE-FM2) forms of the
F protein. Distinctive expression of the F protein was identified in HEp-2 cells transfected with the different
recombinant vectors using ELISA and immunofluorescence. Mice immunization verified the potential for
recombinant vectors to elicit significant levels of neutralizing antibodies and CD8C T-cell lymphocytes.
pPOE-TF showed higher levels of gene expression in cell culture and better induction of the humoral and
cellular immune responses. Following virus challenge, mice that had been immunized with the
recombinant vectors were able to control virus replication and displayed lower inflammation compared
with mice immunized with empty pPOE vector or formalin-inactivated HRSV vaccine. Moreover,
pulmonary cytokine profiles of mice immunized with the 3 recombinant vectors were similar to those of
the mock infected group. In conclusion, recombinant pPOE vectors are promising HRSV vaccine
candidates in terms of their safety, immunogenicity and protective efficiency. These data encourage
further evaluation in phase I clinical trials.
Respiratory tract infections are a principal cause of illness and mortality in children worldwide... more Respiratory tract infections are a principal cause of illness and mortality in children worldwide and mostly caused by viruses. In this study, the epidemiology of 11 respiratory RNA viruses was investigated in a cohort of hospitalized children at a tertiary referral center in Riyadh from February 2008 to March 2009 using conventional and real-time monoplex RT-PCR assays. Among 174 nasopharyngeal aspirates, respiratory syncytial virus (RSV) was detected in 39 samples (22.41%), influenza A virus in 34 (19.54%), metapneumovirus (MPV) in 19 (10.92%), coronaviruses in 14 (8.05%), and parainfluenza viruses (PIVs) in 11 (6.32%). RSV, PIVs and coronaviruses were most prevalent in infants less than 6 months old, MPV and influenza A virus were more prominent in children aged 7-24 and 25-60 months, respectively. The majority of the viruses were identified during winter with two peaks observed in March 2008 and January 2009. The presented data warrants further investigation to understand the epidemiology of respiratory viruses in Saudi Arabia on spatial and temporal basis. This article is protected by copyright. All rights reserved.
Human respiratory syncytial virus (HRSV) infections have worldwide records. The virus is responsi... more Human respiratory syncytial virus (HRSV) infections have worldwide records. The virus is responsible for bronchiolitis, pneumonia, and asthma in humans of different age groups. Premature infants, young children, and immunocompromised individuals are prone to severe HRSV infection that may lead to death. Based on worldwide estimations, millions of cases were reported in both developed and developing countries. In fact, HRSV symptoms develop mainly as a result of host immune response. Due to inability to establish long lasting adaptive immunity, HRSV infection is recurrent and hence impairs vaccine development. Once HRSV attached to the airway epithelia, interaction with the host innate immune components starts. HRSV interaction with pulmonary innate defenses is crucial in determining the disease outcome. Infection of alveolar epithelial cells triggers a cascade of events that lead to recruitment and activation of leukocyte populations. HRSV clearance is mediated by a number of innate leukocytes, including macrophages, natural killer cells, eosinophils, dendritic cells, and neutrophils. Regulation of these cells is mediated by cytokines, chemokines, and other immune mediators. Although the innate immune system helps to clear HRSV infection, it participates in disease progression such as bronchiolitis and asthma. Resolving the mechanisms by which HRSV induces pathogenesis, different possible interactions between the virus and immune components, and immune cells interplay are essential for developing new effective vaccines. Therefore, the current review focuses on how the pulmonary innate defenses mediate HRSV clearance and to what extent they participate in disease progression. In addition, immune responses associated with HRSV vaccines will be discussed.
Human respiratory syncytial virus (HRSV) is a frequent cause of hospitalization and mortality in ... more Human respiratory syncytial virus (HRSV) is a frequent cause of hospitalization and mortality in children worldwide. The molecular epidemiology and circulation pattern of HRSV in Saudi Arabia is mostly uncharted. In the current study, the genetic variability and phylogenetic relationships of HRSV type A strains circulating in Riyadh Province were explored. Nasopharyngeal aspirates were collected from hospitalized children with acute respiratory symptoms during the winter-spring seasons of 2007/08 and 2008/09. Among 175 samples analyzed, 39 (22.3 %) were positive for HRSV by one-step RT-PCR (59 % type A and 41 % type B). Propagation of positive samples in HEp-2 cells permitted the recovery of the first Saudi HRSV isolates. Genetic variability among Saudi HRSV-A strains was evaluated by sequence analysis of the complete attachment (G) protein gene. The nucleotide sequence was compared to representatives of the previously identified HRSV-A genotypes. Sequence and phylogenetic analysis showed that the strains examined in this study were very closely related at both the nucleotide and amino acid level, and all of them are clustered in the GA2 genotype (and mostly belonged to the NA-1 subtype). A total of 23 mutation sites, 14 of which resulted in an amino acid change, were recorded only in Saudi strains. This is the first report on genetic diversity of HRSV-A strains in Saudi Arabia. Further analysis of strains on a geographical and temporal basis is needed to fully understand HRSV-A circulation patterns in Saudi Arabia.
Several infectious diseases, such as polio, measles, diphtheria, rubella, mumps and tetanus can b... more Several infectious diseases, such as polio, measles, diphtheria, rubella, mumps and tetanus can be controlled and, in many cases, be eradicated with current vaccines.