Prof. Fielding is the Director: Research Innovation and the Principal Investigator: Molecular Bio... more Prof. Fielding is the Director: Research Innovation and the Principal Investigator: Molecular Biology and Virology Research Laboratory Department of Medical BioSciences, at the University of the Western Cape. He has been working on Human Coronaviruses since 2003, and, therefore, has many years of experience surrounding this topic.
Die Minister van Gesondheid, dr. Zweli Mkhize, sê Suid-Afrika ondervind amptelik sy tweede vlaag ... more Die Minister van Gesondheid, dr. Zweli Mkhize, sê Suid-Afrika ondervind amptelik sy tweede vlaag van COVID-19-infeksies. Ons het by 'n kenner gaan hoor wat dit inhou in die onmiddelike stryd teen die virus. Die DA pronk oor sy bydraes in die parlement in 2020, maar wat dink kiesers van die party? Ons praat met 'n ontleder oor gister se tussenverkiesings.<br>Daar is diegene wat meen die nuwe lugredery, Lift, 'n dapper stap doen om in hierdie ekonomiese tye sy toetrede tot die plaaslike lugvaartbedryf te maak. Lugvaartekonoom Joachim Vermooten meen egter dis 'n sinvolle stap.
Health Minister Zweli Mkhize recently announced that the isolation period for COVID 19 patients h... more Health Minister Zweli Mkhize recently announced that the isolation period for COVID 19 patients has been reduced from 14 to ten days. This is on condition that the patient does not have a fever and the symptoms are improving. Minister Mkhize also says asymptomatic patients are to self-isolate for eight days. Professor Burtram Fielding disagrees with this position…<br>Guest: Professor Burtram Fielding - University of Western Cape Director Research Development and a coronavirus expert
Burtram Fielding | Molecular biologist and Director of Research Development at University Of West... more Burtram Fielding | Molecular biologist and Director of Research Development at University Of Western Cape
We're back and once again joined by Coronavirus expert Prof Burtram Fielding from UWC. Join u... more We're back and once again joined by Coronavirus expert Prof Burtram Fielding from UWC. Join us as we discuss the reason behind the National Lockdown, as well as get caught up to date with the latest information regarding the Global Coronavirus Pandemic.
Over the past 18 years, three highly pathogenic human (h) coronaviruses (CoVs) have caused severe... more Over the past 18 years, three highly pathogenic human (h) coronaviruses (CoVs) have caused severe outbreaks, the most recent causative agent, SARS-CoV-2, being the first to cause a pandemic. Although much progress has been made since the COVID-19 pandemic started, much about SARS-CoV-2 and its disease, COVID-19, is still poorly understood. The highly pathogenic hCoVs differ in some respects, but also share some similarities in clinical presentation, the risk factors associated with severe disease, and the characteristic immunopathology associated with the progression to severe disease. This review aims to highlight these overlapping aspects of the highly pathogenic hCoVs—SARS-CoV, MERS-CoV, and SARS-CoV-2—briefly discussing the importance of an appropriately regulated immune response; how the immune response to these highly pathogenic hCoVs might be dysregulated through interferon (IFN) inhibition, antibody-dependent enhancement (ADE), and long non-coding RNA (lncRNA); and how these...
Human (h) coronaviruses (CoVs) 229E, NL63, OC43, and HKU1 are less virulent and cause mild, self-... more Human (h) coronaviruses (CoVs) 229E, NL63, OC43, and HKU1 are less virulent and cause mild, self-limiting respiratory tract infections, while SARS-CoV, MERS-CoV, and SARS-CoV-2, are more virulent and have caused severe outbreaks. The CoV envelope (E) protein, an important contributor to the pathogenesis of severe hCoVs infections, may provide insight into this disparate severity of the disease. Topology prediction programs and 3D modelling software was used to predict and visualize structural aspects of the hCoV E protein related to its functions. All seven hCoV E proteins largely adopted different topologies, with some distinction between the more virulent and less virulent ones. The 3D models refined this distinction, showing the PDZ-binding motif (PBM) of SARS-CoV, MERS-CoV, and SARS-CoV-2 to be more flexible than the PBM of hCoVs 229E, NL63, OC43, and HKU1. We speculate that the increased flexibility of the PBM may provide the more virulent hCoVs with a greater degree of freedom...
Severe acute respiratory syndrome coronavirus (SARS-CoV) 7a is an accessory protein with no known... more Severe acute respiratory syndrome coronavirus (SARS-CoV) 7a is an accessory protein with no known homologues. In this study, we report the interaction of a SARS-CoV 7a and small glutamine-rich tetratricopeptide repeat-containing protein (SGT). SARS-CoV 7a and human SGT interaction was identified using a two-hybrid system screen and confirmed with interaction screens in cell culture and cellular co-localization studies. The SGT domain of interaction was mapped by deletion mutant analysis and results indicated that tetratricopeptide repeat 2 (aa 125-158) was essential for interaction. We also showed that 7a interacted with SARS-CoV structural proteins M (membrane) and E (envelope), which have been shown to be essential for virus-like particle formation. Taken together, our results coupled with data from studies of the interaction between SGT and HIV-1 vpu indicated that SGT could be involved in the life-cycle, possibly assembly of SARS-CoV. Coronaviruses are members of the Coronavirid...
It has been reported in some studies that the newly discovered human coronavirus NL-63 (HCoVNL63)... more It has been reported in some studies that the newly discovered human coronavirus NL-63 (HCoVNL63) is one of the most common coronaviruses associated with acute respiratory infections. HCoVNL63 was first isolated in 2004 from a 7 month old infant in Holland. The HCoV-NL63 genome encodes for one accessory protein, ORF3. This reports the computational analysis of human coronavirus NL63 ORF3 by comparing the amino acid sequences of coronavirus ORF3-homologues. The HCoV-NL63 ORF3 gene was found to encode a putative protein ~25.6 kDa in size. ORF3 was predicted to contain three potential transmembrane regions. The amino acid sequence of HCoVNL63 ORF3 was shown to be most similar to HCoV 229E ORF4 (43% identity; 62% similarity).
Klebsiella pneumoniae is a significant human pathogen causing community and nosocomial infection.... more Klebsiella pneumoniae is a significant human pathogen causing community and nosocomial infection. The use of carbapenem has increased since the spread of extended-spectrum β-lactamase (ESBL) resulting in the emergence of carbapenem resistant K. pneumoniae (CRKP). Due to the continued use of colistin for treatment of infections by CRKP, resistance to colistin has also been reported in several countries and become a major public health concern. Background: National surveillance of antimicrobial resistance has become a mandatory approach to control the spread of antimicrobial resistance and for the establishment of antibiotic treatment guidelines. In this study, clinical isolates of K. pneumoniae were phenotypically investigated for the presences of Colistin and beta-lactams resistance. Methods: Clinical samples were obtained from hospitalised (n=140) and non-hospitalised patients (n= 60) in Misrata, Libya. Identification of the isolated species was achieved using VITEK 2 compact system. Screening for Carbapenem and Cephalosporin-resistance was performed using the disk diffusion method with Carbapenem (10µg) and Cephalosporin (30 µg) disks and Minimum Inhibitory Concentration (MIC) determined by VITEK 2. Colistin resistance was determined using both Sensititre Gram-negative Xtra plate format (GNX2F) and VITEK 2. Carbapenememase activity was detected using the RAPIDEC CARBA NP, Modified Hodge test, Carbapenem inactivation method, MAST Combi Carba plus kit (D73C) and Meropenem combined disk test. ESBL and AmpC production was confirmed using Sensititre ESBL confirmatory plates (ESB1F), modified double disc synergy test MDDST, MAST ESBL detection kit D67C, AmpC &amp; ESBL detection kit D68C along with AmpC detection kit D69C. Results and conclusion: Of the 200 clinical isolates, 85 (42.5%) were K. pneumoniae of which 54 (63.52%) demonstrated resistance to at least one of the Carbapenems, 16 (18.82%) were ESBL or AmpC producers and 2 (2.35%) were Carbapenem and Colistin resistant. 13 (21.25%) isolates were susceptible to all antibiotics tested except Ampicillin and Augmentin.
Drug repurposing for COVID-19 has several potential benefits including shorter development time, ... more Drug repurposing for COVID-19 has several potential benefits including shorter development time, reduced costs and regulatory support for faster time to market for treatment that can alleviate the current pandemic. The current study used molecular docking, molecular dynamics and protein-protein interaction simulations to predict drugs from the Drug Bank that can bind to the SARS-CoV-2 spike protein interacting surface on the human angiotensin-converting enzyme 2 (hACE2) receptor. The study predicted a number of peptide-based drugs, including Sar9 Met (O2)11-Substance P and BV2, that might bind sufficiently to the hACE2 receptor to modulate the protein-protein interaction required for infection by the SARS-CoV-2 virus. Such drugs could be validated in vitro or in vivo as potential inhibitors of the interaction of SARS-CoV-2 spike protein with the human angiotensin-converting enzyme 2 (hACE2) in the airway. Exploration of the proposed and current pharmacological indications of the pep...
Seven human coronaviruses (hCoVs) are known to infect humans. The most recent one, SARS-CoV-2, wa... more Seven human coronaviruses (hCoVs) are known to infect humans. The most recent one, SARS-CoV-2, was isolated and identified in January 2020 from a patient presenting with severe respiratory illness in Wuhan, China. Even though viral coinfections have the potential to influence the resultant disease pattern in the host, very few studies have looked at the disease outcomes in patients infected with both HIV and hCoVs. Groups are now reporting that even though HIV-positive patients can be infected with hCoVs, the likelihood of developing severe CoV-related diseases in these patients is often similar to what is seen in the general population. This review aimed to summarize the current knowledge of coinfections reported for HIV and hCoVs. Moreover, based on the available data, this review aimed to theorize why HIV-positive patients do not frequently develop severe CoV-related diseases.
Alkaloids are a class of natural products known to have wide pharmacological activity and have gr... more Alkaloids are a class of natural products known to have wide pharmacological activity and have great potential for the development of new drugs to treat a wide array of pathologies. Some alkaloids have antiviral activity and/or have been used as prototypes in the development of synthetic antiviral drugs. In this study, eleven anti-coronavirus alkaloids were identified from the scientific literature and their potential therapeutic value against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is discussed. In this study, in silico studies showed an affinity of the alkaloids for binding to the receptor-binding domain of the SARS-CoV-2 spike protein, putatively preventing it from binding to the host cell. Lastly, several mechanisms for the known anti-coronavirus activity of alkaloids were discussed, showing that the alkaloids are interesting compounds with potential use as bioactive agents against SARS-CoV-2.
Human coronaviruses cause both upper and lower respiratory tract infections in humans. In 2012 a ... more Human coronaviruses cause both upper and lower respiratory tract infections in humans. In 2012 a sixth human coronavirus (hCoV) was isolated from a patient presenting with severe respiratory illness. The 60-year-old man died as a result of renal and respiratory failure after admission to a hospital in Jeddah, Saudi Arabia. The aetiological agent was eventually identified as a coronavirus and designated Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV has now been reported in more than 27 countries across the Middle East, Europe, North Africa and Asia. As of July 2017, 2040 MERS-CoV laboratory confirmed cases, resulting in 712 deaths, were reported globally, with a majority of these cases from the Arabian Peninsula. This review summarises the current understanding of MERS-CoV, with special reference to the (i) genome structure, (ii) clinical features, (iii) diagnosis of infection and (iv) treatment and vaccine development.
Human coronaviruses represent a significant disease burden; however, there is currently no antivi... more Human coronaviruses represent a significant disease burden; however, there is currently no antiviral strategy to combat infection. The outbreak of severe acute respiratory syndrome (SARS) in 2003 and Middle East respiratory syndrome (MERS) less than 10 years later demonstrates the potential of coronaviruses to cross species boundaries and further highlights the importance of identifying novel lead compounds with broad spectrum activity. The coronavirus 3CL(pro) provides a highly validated drug target and as there is a high degree of sequence homology and conservation in main chain architecture the design of broad spectrum inhibitors is viable. The ZINC drugs-now library was screened in a consensus high-throughput pharmacophore modeling and molecular docking approach by Vina, Glide, GOLD and MM-GBSA. Molecular dynamics further confirmed results obtained from structure-based techniques. A highly defined hit-list of 19 compounds was identified by the structure-based drug design methodo...
Prof. Fielding is the Director: Research Innovation and the Principal Investigator: Molecular Bio... more Prof. Fielding is the Director: Research Innovation and the Principal Investigator: Molecular Biology and Virology Research Laboratory Department of Medical BioSciences, at the University of the Western Cape. He has been working on Human Coronaviruses since 2003, and, therefore, has many years of experience surrounding this topic.
Die Minister van Gesondheid, dr. Zweli Mkhize, sê Suid-Afrika ondervind amptelik sy tweede vlaag ... more Die Minister van Gesondheid, dr. Zweli Mkhize, sê Suid-Afrika ondervind amptelik sy tweede vlaag van COVID-19-infeksies. Ons het by 'n kenner gaan hoor wat dit inhou in die onmiddelike stryd teen die virus. Die DA pronk oor sy bydraes in die parlement in 2020, maar wat dink kiesers van die party? Ons praat met 'n ontleder oor gister se tussenverkiesings.<br>Daar is diegene wat meen die nuwe lugredery, Lift, 'n dapper stap doen om in hierdie ekonomiese tye sy toetrede tot die plaaslike lugvaartbedryf te maak. Lugvaartekonoom Joachim Vermooten meen egter dis 'n sinvolle stap.
Health Minister Zweli Mkhize recently announced that the isolation period for COVID 19 patients h... more Health Minister Zweli Mkhize recently announced that the isolation period for COVID 19 patients has been reduced from 14 to ten days. This is on condition that the patient does not have a fever and the symptoms are improving. Minister Mkhize also says asymptomatic patients are to self-isolate for eight days. Professor Burtram Fielding disagrees with this position…<br>Guest: Professor Burtram Fielding - University of Western Cape Director Research Development and a coronavirus expert
Burtram Fielding | Molecular biologist and Director of Research Development at University Of West... more Burtram Fielding | Molecular biologist and Director of Research Development at University Of Western Cape
We're back and once again joined by Coronavirus expert Prof Burtram Fielding from UWC. Join u... more We're back and once again joined by Coronavirus expert Prof Burtram Fielding from UWC. Join us as we discuss the reason behind the National Lockdown, as well as get caught up to date with the latest information regarding the Global Coronavirus Pandemic.
Over the past 18 years, three highly pathogenic human (h) coronaviruses (CoVs) have caused severe... more Over the past 18 years, three highly pathogenic human (h) coronaviruses (CoVs) have caused severe outbreaks, the most recent causative agent, SARS-CoV-2, being the first to cause a pandemic. Although much progress has been made since the COVID-19 pandemic started, much about SARS-CoV-2 and its disease, COVID-19, is still poorly understood. The highly pathogenic hCoVs differ in some respects, but also share some similarities in clinical presentation, the risk factors associated with severe disease, and the characteristic immunopathology associated with the progression to severe disease. This review aims to highlight these overlapping aspects of the highly pathogenic hCoVs—SARS-CoV, MERS-CoV, and SARS-CoV-2—briefly discussing the importance of an appropriately regulated immune response; how the immune response to these highly pathogenic hCoVs might be dysregulated through interferon (IFN) inhibition, antibody-dependent enhancement (ADE), and long non-coding RNA (lncRNA); and how these...
Human (h) coronaviruses (CoVs) 229E, NL63, OC43, and HKU1 are less virulent and cause mild, self-... more Human (h) coronaviruses (CoVs) 229E, NL63, OC43, and HKU1 are less virulent and cause mild, self-limiting respiratory tract infections, while SARS-CoV, MERS-CoV, and SARS-CoV-2, are more virulent and have caused severe outbreaks. The CoV envelope (E) protein, an important contributor to the pathogenesis of severe hCoVs infections, may provide insight into this disparate severity of the disease. Topology prediction programs and 3D modelling software was used to predict and visualize structural aspects of the hCoV E protein related to its functions. All seven hCoV E proteins largely adopted different topologies, with some distinction between the more virulent and less virulent ones. The 3D models refined this distinction, showing the PDZ-binding motif (PBM) of SARS-CoV, MERS-CoV, and SARS-CoV-2 to be more flexible than the PBM of hCoVs 229E, NL63, OC43, and HKU1. We speculate that the increased flexibility of the PBM may provide the more virulent hCoVs with a greater degree of freedom...
Severe acute respiratory syndrome coronavirus (SARS-CoV) 7a is an accessory protein with no known... more Severe acute respiratory syndrome coronavirus (SARS-CoV) 7a is an accessory protein with no known homologues. In this study, we report the interaction of a SARS-CoV 7a and small glutamine-rich tetratricopeptide repeat-containing protein (SGT). SARS-CoV 7a and human SGT interaction was identified using a two-hybrid system screen and confirmed with interaction screens in cell culture and cellular co-localization studies. The SGT domain of interaction was mapped by deletion mutant analysis and results indicated that tetratricopeptide repeat 2 (aa 125-158) was essential for interaction. We also showed that 7a interacted with SARS-CoV structural proteins M (membrane) and E (envelope), which have been shown to be essential for virus-like particle formation. Taken together, our results coupled with data from studies of the interaction between SGT and HIV-1 vpu indicated that SGT could be involved in the life-cycle, possibly assembly of SARS-CoV. Coronaviruses are members of the Coronavirid...
It has been reported in some studies that the newly discovered human coronavirus NL-63 (HCoVNL63)... more It has been reported in some studies that the newly discovered human coronavirus NL-63 (HCoVNL63) is one of the most common coronaviruses associated with acute respiratory infections. HCoVNL63 was first isolated in 2004 from a 7 month old infant in Holland. The HCoV-NL63 genome encodes for one accessory protein, ORF3. This reports the computational analysis of human coronavirus NL63 ORF3 by comparing the amino acid sequences of coronavirus ORF3-homologues. The HCoV-NL63 ORF3 gene was found to encode a putative protein ~25.6 kDa in size. ORF3 was predicted to contain three potential transmembrane regions. The amino acid sequence of HCoVNL63 ORF3 was shown to be most similar to HCoV 229E ORF4 (43% identity; 62% similarity).
Klebsiella pneumoniae is a significant human pathogen causing community and nosocomial infection.... more Klebsiella pneumoniae is a significant human pathogen causing community and nosocomial infection. The use of carbapenem has increased since the spread of extended-spectrum β-lactamase (ESBL) resulting in the emergence of carbapenem resistant K. pneumoniae (CRKP). Due to the continued use of colistin for treatment of infections by CRKP, resistance to colistin has also been reported in several countries and become a major public health concern. Background: National surveillance of antimicrobial resistance has become a mandatory approach to control the spread of antimicrobial resistance and for the establishment of antibiotic treatment guidelines. In this study, clinical isolates of K. pneumoniae were phenotypically investigated for the presences of Colistin and beta-lactams resistance. Methods: Clinical samples were obtained from hospitalised (n=140) and non-hospitalised patients (n= 60) in Misrata, Libya. Identification of the isolated species was achieved using VITEK 2 compact system. Screening for Carbapenem and Cephalosporin-resistance was performed using the disk diffusion method with Carbapenem (10µg) and Cephalosporin (30 µg) disks and Minimum Inhibitory Concentration (MIC) determined by VITEK 2. Colistin resistance was determined using both Sensititre Gram-negative Xtra plate format (GNX2F) and VITEK 2. Carbapenememase activity was detected using the RAPIDEC CARBA NP, Modified Hodge test, Carbapenem inactivation method, MAST Combi Carba plus kit (D73C) and Meropenem combined disk test. ESBL and AmpC production was confirmed using Sensititre ESBL confirmatory plates (ESB1F), modified double disc synergy test MDDST, MAST ESBL detection kit D67C, AmpC &amp; ESBL detection kit D68C along with AmpC detection kit D69C. Results and conclusion: Of the 200 clinical isolates, 85 (42.5%) were K. pneumoniae of which 54 (63.52%) demonstrated resistance to at least one of the Carbapenems, 16 (18.82%) were ESBL or AmpC producers and 2 (2.35%) were Carbapenem and Colistin resistant. 13 (21.25%) isolates were susceptible to all antibiotics tested except Ampicillin and Augmentin.
Drug repurposing for COVID-19 has several potential benefits including shorter development time, ... more Drug repurposing for COVID-19 has several potential benefits including shorter development time, reduced costs and regulatory support for faster time to market for treatment that can alleviate the current pandemic. The current study used molecular docking, molecular dynamics and protein-protein interaction simulations to predict drugs from the Drug Bank that can bind to the SARS-CoV-2 spike protein interacting surface on the human angiotensin-converting enzyme 2 (hACE2) receptor. The study predicted a number of peptide-based drugs, including Sar9 Met (O2)11-Substance P and BV2, that might bind sufficiently to the hACE2 receptor to modulate the protein-protein interaction required for infection by the SARS-CoV-2 virus. Such drugs could be validated in vitro or in vivo as potential inhibitors of the interaction of SARS-CoV-2 spike protein with the human angiotensin-converting enzyme 2 (hACE2) in the airway. Exploration of the proposed and current pharmacological indications of the pep...
Seven human coronaviruses (hCoVs) are known to infect humans. The most recent one, SARS-CoV-2, wa... more Seven human coronaviruses (hCoVs) are known to infect humans. The most recent one, SARS-CoV-2, was isolated and identified in January 2020 from a patient presenting with severe respiratory illness in Wuhan, China. Even though viral coinfections have the potential to influence the resultant disease pattern in the host, very few studies have looked at the disease outcomes in patients infected with both HIV and hCoVs. Groups are now reporting that even though HIV-positive patients can be infected with hCoVs, the likelihood of developing severe CoV-related diseases in these patients is often similar to what is seen in the general population. This review aimed to summarize the current knowledge of coinfections reported for HIV and hCoVs. Moreover, based on the available data, this review aimed to theorize why HIV-positive patients do not frequently develop severe CoV-related diseases.
Alkaloids are a class of natural products known to have wide pharmacological activity and have gr... more Alkaloids are a class of natural products known to have wide pharmacological activity and have great potential for the development of new drugs to treat a wide array of pathologies. Some alkaloids have antiviral activity and/or have been used as prototypes in the development of synthetic antiviral drugs. In this study, eleven anti-coronavirus alkaloids were identified from the scientific literature and their potential therapeutic value against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is discussed. In this study, in silico studies showed an affinity of the alkaloids for binding to the receptor-binding domain of the SARS-CoV-2 spike protein, putatively preventing it from binding to the host cell. Lastly, several mechanisms for the known anti-coronavirus activity of alkaloids were discussed, showing that the alkaloids are interesting compounds with potential use as bioactive agents against SARS-CoV-2.
Human coronaviruses cause both upper and lower respiratory tract infections in humans. In 2012 a ... more Human coronaviruses cause both upper and lower respiratory tract infections in humans. In 2012 a sixth human coronavirus (hCoV) was isolated from a patient presenting with severe respiratory illness. The 60-year-old man died as a result of renal and respiratory failure after admission to a hospital in Jeddah, Saudi Arabia. The aetiological agent was eventually identified as a coronavirus and designated Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV has now been reported in more than 27 countries across the Middle East, Europe, North Africa and Asia. As of July 2017, 2040 MERS-CoV laboratory confirmed cases, resulting in 712 deaths, were reported globally, with a majority of these cases from the Arabian Peninsula. This review summarises the current understanding of MERS-CoV, with special reference to the (i) genome structure, (ii) clinical features, (iii) diagnosis of infection and (iv) treatment and vaccine development.
Human coronaviruses represent a significant disease burden; however, there is currently no antivi... more Human coronaviruses represent a significant disease burden; however, there is currently no antiviral strategy to combat infection. The outbreak of severe acute respiratory syndrome (SARS) in 2003 and Middle East respiratory syndrome (MERS) less than 10 years later demonstrates the potential of coronaviruses to cross species boundaries and further highlights the importance of identifying novel lead compounds with broad spectrum activity. The coronavirus 3CL(pro) provides a highly validated drug target and as there is a high degree of sequence homology and conservation in main chain architecture the design of broad spectrum inhibitors is viable. The ZINC drugs-now library was screened in a consensus high-throughput pharmacophore modeling and molecular docking approach by Vina, Glide, GOLD and MM-GBSA. Molecular dynamics further confirmed results obtained from structure-based techniques. A highly defined hit-list of 19 compounds was identified by the structure-based drug design methodo...
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