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Gene therapy has come of age on several fronts due to the significant improvements related to targeting, delivery and safety of gene therapy vectors. Classic approaches of non-viral and viral vector based delivery of therapeutic genes to compensate for malfunctioning or deleted genes have been demonstrated in preclinical animal models and clinical trials. In the case of cancer therapy, overexpression of immunostimulatory genes has also demonstrated therapeutic efficacy. Delivery of small interfering, short hairpin and micro-RNA have provided efficient gene silencing by RNA interference as a mode of gene therapy. Moreover, vaccines targeting infectious diseases and promotion of immune stimulation in cancers can be considered as gene therapy applications. More recent approaches comprise of CAR-T technology, where T-cells have been engineered to produce an artificial T-cell receptor for immunotherapy applications. Moreover, CRISPR technologies have substantially widened gene therapy applications, making it possible to specially replace malfunctioning genes with fully functional counterparts.
Kenneth Lundstrom. Gene Therapy. Reference Module in Biomedical Sciences 2021, 1 .
AMA StyleKenneth Lundstrom. Gene Therapy. Reference Module in Biomedical Sciences. 2021; ():1.
Chicago/Turabian StyleKenneth Lundstrom. 2021. "Gene Therapy." Reference Module in Biomedical Sciences , no. : 1.
Two adenovirus-based vaccines, ChAdOx1 nCoV-19 and Ad26.COV2.S, and two mRNA-based vaccines, BNT162b2 and mRNA.1273, have been approved by the European Medicines Agency (EMA), and are invaluable in preventing and reducing the incidence of coronavirus disease-2019 (COVID-19). Recent reports have pointed to thrombosis with associated thrombocytopenia as an adverse effect occurring at a low frequency in some individuals after vaccination. The causes of such events may be related to SARS-CoV-2 spike protein interactions with different C-type lectin receptors, heparan sulfate proteoglycans (HSPGs) and the CD147 receptor, or to different soluble splice variants of the spike protein, adenovirus vector interactions with the CD46 receptor or platelet factor 4 antibodies. Similar findings have been reported for several viral diseases after vaccine administration. In addition, immunological mechanisms elicited by viral vectors related to cellular delivery could play a relevant role in individuals with certain genetic backgrounds. Although rare, the potential COVID-19 vaccine-induced immune thrombotic thrombocytopenia (VITT) requires immediate validation, especially in risk groups, such as the elderly, chronic smokers, and individuals with pre-existing incidences of thrombocytopenia; and if necessary, a reformulation of existing vaccines.
Kenneth Lundstrom; Debmalya Barh; Bruce Uhal; Kazuo Takayama; Alaa Aljabali; Tarek Abd El-Aziz; Amos Lal; ElRashdy Redwan; Parise Adadi; Gaurav Chauhan; Samendra Sherchan; Gajendra Azad; Nima Rezaei; Ángel Serrano-Aroca; Nicolas Bazan; Sk Hassan; Pritam Panda; Pabitra Pal Choudhury; Damiano Pizzol; Ramesh Kandimalla; Wagner Baetas-Da-Cruz; Yogendra Mishra; Giorgio Palu; Adam Brufsky; Murtaza Tambuwala; Vladimir Uversky. COVID-19 Vaccines and Thrombosis—Roadblock or Dead-End Street? Biomolecules 2021, 11, 1020 .
AMA StyleKenneth Lundstrom, Debmalya Barh, Bruce Uhal, Kazuo Takayama, Alaa Aljabali, Tarek Abd El-Aziz, Amos Lal, ElRashdy Redwan, Parise Adadi, Gaurav Chauhan, Samendra Sherchan, Gajendra Azad, Nima Rezaei, Ángel Serrano-Aroca, Nicolas Bazan, Sk Hassan, Pritam Panda, Pabitra Pal Choudhury, Damiano Pizzol, Ramesh Kandimalla, Wagner Baetas-Da-Cruz, Yogendra Mishra, Giorgio Palu, Adam Brufsky, Murtaza Tambuwala, Vladimir Uversky. COVID-19 Vaccines and Thrombosis—Roadblock or Dead-End Street? Biomolecules. 2021; 11 (7):1020.
Chicago/Turabian StyleKenneth Lundstrom; Debmalya Barh; Bruce Uhal; Kazuo Takayama; Alaa Aljabali; Tarek Abd El-Aziz; Amos Lal; ElRashdy Redwan; Parise Adadi; Gaurav Chauhan; Samendra Sherchan; Gajendra Azad; Nima Rezaei; Ángel Serrano-Aroca; Nicolas Bazan; Sk Hassan; Pritam Panda; Pabitra Pal Choudhury; Damiano Pizzol; Ramesh Kandimalla; Wagner Baetas-Da-Cruz; Yogendra Mishra; Giorgio Palu; Adam Brufsky; Murtaza Tambuwala; Vladimir Uversky. 2021. "COVID-19 Vaccines and Thrombosis—Roadblock or Dead-End Street?" Biomolecules 11, no. 7: 1020.
It is well established that pre-existing comorbid conditions such as hypertension, diabetes, obesity, cardiovascular diseases (CVDs), chronic kidney diseases (CKDs), cancers, and chronic obstructive pulmonary disease (COPD) are associated with increased severity and fatality of COVID-19. The increased death from COVID-19 is due to the unavailability of a gold standard therapeutic and, more importantly, the lack of understanding of how the comorbid conditions and COVID-19 interact at the molecular level, so that personalized management strategies can be adopted. Here, using multi-omics data sets and bioinformatics strategy, we identified the pathway crosstalk between COVID-19 and diabetes, hypertension, CVDs, CKDs, and cancers. Further, shared pathways and hub gene-based targets for COVID-19 and its associated specific and combination of comorbid conditions are also predicted towards developing personalized management strategies. The approved drugs for most of these identified targets are also provided towards drug repurposing. Literature supports the involvement of our identified shared pathways in pathogenesis of COVID-19 and development of the specific comorbid condition of interest. Similarly, shared pathways- and hub gene-based targets are also found to have potential implementations in managing COVID-19 patients. However, the identified targets and drugs need further careful evaluation for their repurposing towards personalized treatment of COVID-19 cases having pre-existing specific comorbid conditions we have considered in this analysis. The method applied here may also be helpful in identifying common pathway components and targets in other disease-disease interactions too.
Debmalya Barh; Alaa Aljabali; Murtaza Tambuwala; Sandeep Tiwari; Ángel Serrano-Aroca; Khalid Alzahrani; Bruno Silva Andrade; Vasco Azevedo; Nirmal Ganguly; Kenneth Lundstrom. Predicting COVID-19—Comorbidity Pathway Crosstalk-Based Targets and Drugs: Towards Personalized COVID-19 Management. Biomedicines 2021, 9, 556 .
AMA StyleDebmalya Barh, Alaa Aljabali, Murtaza Tambuwala, Sandeep Tiwari, Ángel Serrano-Aroca, Khalid Alzahrani, Bruno Silva Andrade, Vasco Azevedo, Nirmal Ganguly, Kenneth Lundstrom. Predicting COVID-19—Comorbidity Pathway Crosstalk-Based Targets and Drugs: Towards Personalized COVID-19 Management. Biomedicines. 2021; 9 (5):556.
Chicago/Turabian StyleDebmalya Barh; Alaa Aljabali; Murtaza Tambuwala; Sandeep Tiwari; Ángel Serrano-Aroca; Khalid Alzahrani; Bruno Silva Andrade; Vasco Azevedo; Nirmal Ganguly; Kenneth Lundstrom. 2021. "Predicting COVID-19—Comorbidity Pathway Crosstalk-Based Targets and Drugs: Towards Personalized COVID-19 Management." Biomedicines 9, no. 5: 556.
The current COVID-19 pandemic has cast a new light on the translational process from basic academic virology research to prophylactic and therapeutic interventions of safe and efficient antiviral drugs and vaccines in humans. Until recently, virologists were left much unnoticed by the general public in their chambers working on, for the naked eye, invisible infectious agents, keeping viruses such as polio, measles, and mumps at bay with reliable conventional vaccines and producing annual modifications to influenza vaccines to outsmart the novel annual mutant influenza viruses causing outbreaks during the flu season. Then, everything changed! The SARS-CoV-2 outbreak was declared a pandemic by the World Health Organization reaching every corner of the world, and today (February 12, 2021) (https://www.worldometers.info/coronavirus/?#countries) more than 108 million people have been infected, leading to the death of more than 2.3 million people and the devastation of the global economy. An unprecedented combined effort saw the scientific community, pharmaceutical and biotech companies, and governmental organizations acting together at a level never seen before. The biggest and fastest translational virology program was born! There is no better example of the power of translational medicine, especially translational virology, than what has been illustrated by the record-breaking development of several approved vaccines against SARS-CoV-2. This effort required substantial breakthrough in technology development at all stages from basic research level to clinical applications. In this context, the innovation at the bench, the rapid evaluation in animal models followed by overlapping phase I to III clinical trials and vaccine production at a stage when vaccine safety and efficacy had not been confirmed (1) showed the dedication and the determination of the whole scientific community. It resulted in approval of three different vaccines within more or less a year since the first detection of SARS-CoV-2. Moreover, two additional adenovirus-based vaccines have been approved and more are expected to follow. Although RNA-based vaccines “won the vaccine race,” the approval of the simian adenovirus-based vaccine confirmed the power of translational virology. Actually, viral components such as methyl guanosine analogs (m7G) for 5′ end capping of RNA and the formulation of viral-like nanoparticles for the delivery of RNA also played an essential role in RNA vaccine development. Despite the successful rapid development of vaccines against COVID-19, the recent emergence of SARS-CoV-2 variants with enhanced transmissibility and potential pathogenicity (2) has underlined the importance of staying alert by applying translational virology approaches for identification of new mutations in the population and to confirm the efficacy of existing vaccines or engineering new vaccines targeting emerging variants of SARS-CoV-2. At the same time as COVID-19 vaccine development was initiated, major efforts to develop antiviral drugs for the treatment of COVID-19 started. Much attention has been paid to repurposing drugs previously developed for other viral infections (3, 4). In this context, remdesivir, an inhibitor of RNA-dependent RNA polymerase, which was originally developed for treatment of hepatitis C virus (HCV), respiratory syncytial virus (RSV), and Ebola virus (EBOV) is evaluated (5). In the case of COVID-19, patients treated with compassionate-use of remdesivir for severe disease showed clinical improvement in 68% of patients although additional studies are required (6). Obviously, major efforts were dedicated to screening potential novel antiviral drugs (7). Moreover, other antiviral drugs and monoclonal antibodies have been developed including the recently FDA approved casirivimab and imdevimab monoclonal antibodies (http://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-monoclonal-antibodies-treatment-covid-19). Although translational research, and in this case translational virology, has been considered as the process of generating new materials and medical evidence for health care needs, the influence of governmental organizations and authorities plays an important role (8) as has been seen for COVID-19 drug and vaccine development. Translational virology can be divided into areas of basic, preclinical and clinical research, drug production, and drug regulation and approval. Basic research is dominated by activities conducted by academic institutions interested in questions related to basic structure and function of viruses, and rarely present opportunities for directly applied approaches. However, systems biology approaches have provided vast amounts of genomics and proteomics information, which has significantly advanced studies on virus-host interactions supporting drug and vaccine development (9). Moreover, complementary short interfering (siRNA) and micro-RNA (miRNA) high-throughput screening technologies and next-generation sequencing have presented a more detailed multidimensional view on virus-host networks. Together with bioinformatics and computational biology, systems biology can have a profound impact on translational research supporting the development of novel therapeutics and vaccines against viral infections. It should also be pointed out that viral vector engineering, which has demonstrated a major impact on both gene therapy and vaccine development, has to a large extent originated from academic institutions (10). Preclinical studies present a step in the direction toward translational medicine represented by evaluation in mammalian cell lines, primary cell cultures and more recently in three-dimensional cell culture models, which range from engineering tissues for clinical applications to development of models for drug screening (11). Tumor models in rodents and primates for the evaluation of cancer drug candidates (12) and...
Kenneth Lundstrom. Translational Virology in the Age of Pandemics. Frontiers in Virology 2021, 1, 1 .
AMA StyleKenneth Lundstrom. Translational Virology in the Age of Pandemics. Frontiers in Virology. 2021; 1 ():1.
Chicago/Turabian StyleKenneth Lundstrom. 2021. "Translational Virology in the Age of Pandemics." Frontiers in Virology 1, no. : 1.
Phylogenetic analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is focused on a single isolate of bat coronaviruses (bat CoVs) which does not adequately represent genetically related coronaviruses (CoVs)
Murat Seyran; Sk. Hassan; Vladimir Uversky; Pabitra Pal Choudhury; Bruce Uhal; Kenneth Lundstrom; Diksha Attrish; Nima Rezaei; Alaa Aljabali; Shinjini Ghosh; Damiano Pizzol; Parise Adadi; Tarek El-Aziz; Ramesh Kandimalla; Murtaza Tambuwala; Amos Lal; Gajendra Azad; Samendra Sherchan; Wagner Baetas-Da-Cruz; Giorgio Palù; Adam Brufsky. Urgent Need for Field Surveys of Coronaviruses in Southeast Asia to Understand the SARS-CoV-2 Phylogeny and Risk Assessment for Future Outbreaks. Biomolecules 2021, 11, 398 .
AMA StyleMurat Seyran, Sk. Hassan, Vladimir Uversky, Pabitra Pal Choudhury, Bruce Uhal, Kenneth Lundstrom, Diksha Attrish, Nima Rezaei, Alaa Aljabali, Shinjini Ghosh, Damiano Pizzol, Parise Adadi, Tarek El-Aziz, Ramesh Kandimalla, Murtaza Tambuwala, Amos Lal, Gajendra Azad, Samendra Sherchan, Wagner Baetas-Da-Cruz, Giorgio Palù, Adam Brufsky. Urgent Need for Field Surveys of Coronaviruses in Southeast Asia to Understand the SARS-CoV-2 Phylogeny and Risk Assessment for Future Outbreaks. Biomolecules. 2021; 11 (3):398.
Chicago/Turabian StyleMurat Seyran; Sk. Hassan; Vladimir Uversky; Pabitra Pal Choudhury; Bruce Uhal; Kenneth Lundstrom; Diksha Attrish; Nima Rezaei; Alaa Aljabali; Shinjini Ghosh; Damiano Pizzol; Parise Adadi; Tarek El-Aziz; Ramesh Kandimalla; Murtaza Tambuwala; Amos Lal; Gajendra Azad; Samendra Sherchan; Wagner Baetas-Da-Cruz; Giorgio Palù; Adam Brufsky. 2021. "Urgent Need for Field Surveys of Coronaviruses in Southeast Asia to Understand the SARS-CoV-2 Phylogeny and Risk Assessment for Future Outbreaks." Biomolecules 11, no. 3: 398.
Vaccine development against SARS-CoV-2 has been fierce due to the devastating COVID-19 pandemic and has included all potential approaches for providing the global community with safe and efficient vaccine candidates in the shortest possible timeframe. Viral vectors have played a central role especially using adenovirus-based vectors. Additionally, other viral vectors based on vaccinia viruses, measles viruses, rhabdoviruses, influenza viruses and lentiviruses have been subjected to vaccine development. Self-amplifying RNA virus vectors have been utilized for lipid nanoparticle-based delivery of RNA as COVID-19 vaccines. Several adenovirus-based vaccine candidates have elicited strong immune responses in immunized animals and protection against challenges in mice and primates has been achieved. Moreover, adenovirus-based vaccine candidates have been subjected to phase I to III clinical trials. Recently, the simian adenovirus-based ChAdOx1 vector expressing the SARS-CoV-2 S spike protein was approved for use in humans in the UK.
Kenneth Lundstrom. Viral Vectors for COVID-19 Vaccine Development. Viruses 2021, 13, 317 .
AMA StyleKenneth Lundstrom. Viral Vectors for COVID-19 Vaccine Development. Viruses. 2021; 13 (2):317.
Chicago/Turabian StyleKenneth Lundstrom. 2021. "Viral Vectors for COVID-19 Vaccine Development." Viruses 13, no. 2: 317.
Kenneth Lundstrom. Immune Responses of Alphavirus Vaccination in Patients with HPV-Induced Cancers. Molecular Therapy 2021, 29, 415 -416.
AMA StyleKenneth Lundstrom. Immune Responses of Alphavirus Vaccination in Patients with HPV-Induced Cancers. Molecular Therapy. 2021; 29 (2):415-416.
Chicago/Turabian StyleKenneth Lundstrom. 2021. "Immune Responses of Alphavirus Vaccination in Patients with HPV-Induced Cancers." Molecular Therapy 29, no. 2: 415-416.
Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that is engendering the severe coronavirus disease 2019 (COVID-19) pandemic. The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 binds to the three sub-domains viz. amino acids (aa) 22–42, aa 79–84, and aa 330–393 of ACE2 on human cells to initiate entry. It was reported earlier that the receptor utilization capacity of ACE2 proteins from different species, such as cats, chimpanzees, dogs, and cattle, are different. A comprehensive analysis of ACE2 receptors of nineteen species was carried out in this study, and the findings propose a possible SARS-CoV-2 transmission flow across these nineteen species.
Sk. Sarif Hassan; Shinjini Ghosh; Diksha Attrish; Pabitra Pal Choudhury; Alaa A. A. Aljabali; Bruce D. Uhal; Kenneth Lundstrom; Nima Rezaei; Vladimir N. Uversky; Murat Seyran; Damiano Pizzol; Parise Adadi; Antonio Soares; Tarek Mohamed Abd El-Aziz; Ramesh Kandimalla; Murtaza M. Tambuwala; Gajendra Kumar Azad; Samendra P. Sherchan; Wagner Baetas-Da-Cruz; Kazuo Takayama; Ángel Serrano-Aroca; Gaurav Chauhan; Giorgio Palu; Adam M. Brufsky. Possible Transmission Flow of SARS-CoV-2 Based on ACE2 Features. Molecules 2020, 25, 5906 .
AMA StyleSk. Sarif Hassan, Shinjini Ghosh, Diksha Attrish, Pabitra Pal Choudhury, Alaa A. A. Aljabali, Bruce D. Uhal, Kenneth Lundstrom, Nima Rezaei, Vladimir N. Uversky, Murat Seyran, Damiano Pizzol, Parise Adadi, Antonio Soares, Tarek Mohamed Abd El-Aziz, Ramesh Kandimalla, Murtaza M. Tambuwala, Gajendra Kumar Azad, Samendra P. Sherchan, Wagner Baetas-Da-Cruz, Kazuo Takayama, Ángel Serrano-Aroca, Gaurav Chauhan, Giorgio Palu, Adam M. Brufsky. Possible Transmission Flow of SARS-CoV-2 Based on ACE2 Features. Molecules. 2020; 25 (24):5906.
Chicago/Turabian StyleSk. Sarif Hassan; Shinjini Ghosh; Diksha Attrish; Pabitra Pal Choudhury; Alaa A. A. Aljabali; Bruce D. Uhal; Kenneth Lundstrom; Nima Rezaei; Vladimir N. Uversky; Murat Seyran; Damiano Pizzol; Parise Adadi; Antonio Soares; Tarek Mohamed Abd El-Aziz; Ramesh Kandimalla; Murtaza M. Tambuwala; Gajendra Kumar Azad; Samendra P. Sherchan; Wagner Baetas-Da-Cruz; Kazuo Takayama; Ángel Serrano-Aroca; Gaurav Chauhan; Giorgio Palu; Adam M. Brufsky. 2020. "Possible Transmission Flow of SARS-CoV-2 Based on ACE2 Features." Molecules 25, no. 24: 5906.
Viral vectors can generate high levels of recombinant protein expression providing the basis for modern vaccine development. A large number of different viral vector expression systems have been utilized for targeting viral surface proteins and tumor-associated antigens. Immunization studies in preclinical animal models have evaluated the elicited humoral and cellular responses and the possible protection against challenges with lethal doses of infectious pathogens or tumor cells. Several vaccine candidates for both infectious diseases and various cancers have been subjected to a number of clinical trials. Human immunization trials have confirmed safe application of viral vectors, generation of neutralizing antibodies and protection against challenges with lethal doses. A special emphasis is placed on COVID-19 vaccines based on viral vectors. Likewise, the flexibility and advantages of applying viral particles, RNA replicons and DNA replicon vectors of self-replicating RNA viruses for vaccine development are presented.
Kenneth Lundstrom. Application of Viral Vectors for Vaccine Development with a Special Emphasis on COVID-19. Viruses 2020, 12, 1324 .
AMA StyleKenneth Lundstrom. Application of Viral Vectors for Vaccine Development with a Special Emphasis on COVID-19. Viruses. 2020; 12 (11):1324.
Chicago/Turabian StyleKenneth Lundstrom. 2020. "Application of Viral Vectors for Vaccine Development with a Special Emphasis on COVID-19." Viruses 12, no. 11: 1324.
The rapid spread of SARS-CoV-2 leading to the COVID-19 pandemic with more than 400,000 deaths worldwide and the global economy shut down has substantially accelerated the research and development of novel and efficient COVID-19 antiviral drugs and vaccines. In the short term, antiviral and other drugs have been subjected to repurposing against COVID-19 demonstrating some success, but some excessively hasty conclusions drawn from significantly suboptimal clinical evaluations have provided false hope. On the other hand, more than 300 potential therapies and at least 150 vaccine studies are in progress at various stages of preclinical or clinical research. The aim here is to provide a timely update of the development, which, due to the intense activities, moves forward with unprecedented speed.
Kenneth Lundstrom. Coronavirus pandemic: treatment and future prevention. Future Microbiology 2020, 15, 1507 -1521.
AMA StyleKenneth Lundstrom. Coronavirus pandemic: treatment and future prevention. Future Microbiology. 2020; 15 (15):1507-1521.
Chicago/Turabian StyleKenneth Lundstrom. 2020. "Coronavirus pandemic: treatment and future prevention." Future Microbiology 15, no. 15: 1507-1521.
The origin of the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) virus causing the COVID-19 pandemic has not yet been fully determined. Despite the consensus about the SARS-CoV-2 origin from bat CoV RaTG13, discrepancy to host tropism to other human Coronaviruses exist. SARS-CoV-2 also possesses some differences in its S protein receptor-binding domain, glycan-binding N-terminal domain and the surface of the sialic acid-binding domain. Despite similarities based on cryo-EM and biochemical studies, the SARS-CoV-2 shows higher stability and binding affinity to the ACE2 receptor. The SARS-CoV-2 does not appear to present a mutational “hot spot” as only the D614G mutation has been identified from clinical isolates. As laboratory manipulation is highly unlikely for the origin of SARS-CoV-2, the current possibilities comprise either natural selection in animal host before zoonotic transfer or natural selection in humans following zoonotic transfer. In the former case, despite SARS-CoV-2 and bat RaTG13 showing 96% identity some pangolin Coronaviruses exhibit very high similarity to particularly the receptor-binding domain of SARS-CoV-2. In the latter case, it can be hypothesized that the SARS-CoV-2 genome has adapted during human-to-human transmission and based on available data, the isolated SARS-CoV-2 genomes derive from a common origin. Before the origin of SARS-CoV-2 can be confirmed additional research is required
Kenneth Lundstrom; Murat Seyran; Damiano Pizzol; Parise Adadi; Tarek Mohamed Abd El-Aziz; Sk. Sarif Hassan; Antonio Soares; Ramesh Kandimalla; Murtaza M. Tambuwala; Alaa A. A. Aljabali; Gajendra Kumar Azad; Pabitra Pal Choudhury; Vladimir N. Uversky; Samendra P. Sherchan; Bruce D. Uhal; Nima Rezaei; Adam M. Brufsky. The Importance of Research on the Origin of SARS-CoV-2. Viruses 2020, 12, 1203 .
AMA StyleKenneth Lundstrom, Murat Seyran, Damiano Pizzol, Parise Adadi, Tarek Mohamed Abd El-Aziz, Sk. Sarif Hassan, Antonio Soares, Ramesh Kandimalla, Murtaza M. Tambuwala, Alaa A. A. Aljabali, Gajendra Kumar Azad, Pabitra Pal Choudhury, Vladimir N. Uversky, Samendra P. Sherchan, Bruce D. Uhal, Nima Rezaei, Adam M. Brufsky. The Importance of Research on the Origin of SARS-CoV-2. Viruses. 2020; 12 (11):1203.
Chicago/Turabian StyleKenneth Lundstrom; Murat Seyran; Damiano Pizzol; Parise Adadi; Tarek Mohamed Abd El-Aziz; Sk. Sarif Hassan; Antonio Soares; Ramesh Kandimalla; Murtaza M. Tambuwala; Alaa A. A. Aljabali; Gajendra Kumar Azad; Pabitra Pal Choudhury; Vladimir N. Uversky; Samendra P. Sherchan; Bruce D. Uhal; Nima Rezaei; Adam M. Brufsky. 2020. "The Importance of Research on the Origin of SARS-CoV-2." Viruses 12, no. 11: 1203.
RNA interference (RNAi) represents a novel approach for alternative antiviral therapy. However, issues related to RNA delivery and stability have presented serious obstacles for obtaining good therapeutic efficacy. Viral vectors are capable of efficient delivery of RNAi as short interfering RNA (siRNA), short hairpin RNA (shRNA) and micro-RNA (miRNA). Efficacy in gene silencing for therapeutic applications against viral diseases has been demonstrated in various animal models. Rotavirus (RV) miR-7 can inhibit rotavirus replication by targeting the RV nonstructural protein 5. Viral gene silencing by targeting the RNAi pathway showed efficient suppression of hepatitis B virus replication by adeno-associated virus (AAV)-based delivery of RNAi hepatitis B virus (HBV) cassettes. Hepatitis C virus replication has been targeted by short hairpin RNA molecules expressed from lentivirus vectors. Potentially, RNAi-based approaches could be suitable for antiviral drugs against COVID-19.
Kenneth Lundstrom. Are Viral Vectors Any Good for RNAi Antiviral Therapy? Viruses 2020, 12, 1189 .
AMA StyleKenneth Lundstrom. Are Viral Vectors Any Good for RNAi Antiviral Therapy? Viruses. 2020; 12 (10):1189.
Chicago/Turabian StyleKenneth Lundstrom. 2020. "Are Viral Vectors Any Good for RNAi Antiviral Therapy?" Viruses 12, no. 10: 1189.
Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that is engendering the severe coronavirus disease 2019 (COVID-19) pandemic. The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 binds to the three sub-domains viz. amino acids (aa) 22-42, aa 79-84, and aa 330-393 of ACE2 on human cells to initiate entry. It was reported earlier that the receptor utilization capacity of ACE2 proteins from different species, such as cats, chimpanzees, dogs, and cattle, are different. A comprehensive analysis of ACE2 receptors of nineteen species was carried out in this study, and the findings propose a possible SARS-CoV-2 transmission flow across these nineteen species.
Sk. Sarif Hassan; Shinjini Ghosh; Diksha Attrish; Pabitra Pal Choudhury; Vladimir N Uversky; Bruce Uhal; Kenneth Lundstrom; Nima Rezaei; Alaa A.A Aljabali; Murat Seyran; Damiano Pizzol; Parise Adadi; Antonio Soares; Tarek Mohamed Abd El-Aziz; Ramesh Kandimalla; Murtaza Tambuwala; Gajendra Kumar Azad; Samendra P. Sherchan; Wagner Baetas-Da-Cruz; Kazuo Takayama; Angel Serrano-Aroca; Gaurav Chauhan; Giorgio Palu; Adam Brufsky. Possible transmission flow of SARS-CoV-2 based on ACE2 features. 2020, 1 .
AMA StyleSk. Sarif Hassan, Shinjini Ghosh, Diksha Attrish, Pabitra Pal Choudhury, Vladimir N Uversky, Bruce Uhal, Kenneth Lundstrom, Nima Rezaei, Alaa A.A Aljabali, Murat Seyran, Damiano Pizzol, Parise Adadi, Antonio Soares, Tarek Mohamed Abd El-Aziz, Ramesh Kandimalla, Murtaza Tambuwala, Gajendra Kumar Azad, Samendra P. Sherchan, Wagner Baetas-Da-Cruz, Kazuo Takayama, Angel Serrano-Aroca, Gaurav Chauhan, Giorgio Palu, Adam Brufsky. Possible transmission flow of SARS-CoV-2 based on ACE2 features. . 2020; ():1.
Chicago/Turabian StyleSk. Sarif Hassan; Shinjini Ghosh; Diksha Attrish; Pabitra Pal Choudhury; Vladimir N Uversky; Bruce Uhal; Kenneth Lundstrom; Nima Rezaei; Alaa A.A Aljabali; Murat Seyran; Damiano Pizzol; Parise Adadi; Antonio Soares; Tarek Mohamed Abd El-Aziz; Ramesh Kandimalla; Murtaza Tambuwala; Gajendra Kumar Azad; Samendra P. Sherchan; Wagner Baetas-Da-Cruz; Kazuo Takayama; Angel Serrano-Aroca; Gaurav Chauhan; Giorgio Palu; Adam Brufsky. 2020. "Possible transmission flow of SARS-CoV-2 based on ACE2 features." , no. : 1.
The current COVID-19 pandemic has substantially accelerated the demands for efficient vaccines. A wide spectrum of approaches includes live attenuated and inactivated viruses, protein subunits and peptides, viral vector-based delivery, DNA plasmids, and synthetic mRNA. Preclinical studies have demonstrated robust immune responses, reduced viral loads and protection against challenges with SARS-CoV-2 in rodents and primates. Vaccine candidates based on all delivery systems mentioned above have been subjected to clinical trials in healthy volunteers. Phase I clinical trials have demonstrated in preliminary findings good safety and tolerability. Evaluation of immune responses in a small number of individuals has demonstrated similar or superior levels of neutralizing antibodies in comparison to immunogenicity detected in COVID-19 patients. Both adenovirus- and mRNA-based vaccines have entered phase II and study protocols for phase III trials with 30,000 participants have been finalized.
Kenneth Lundstrom. The Current Status of COVID-19 Vaccines. Frontiers in Genome Editing 2020, 2, 1 .
AMA StyleKenneth Lundstrom. The Current Status of COVID-19 Vaccines. Frontiers in Genome Editing. 2020; 2 ():1.
Chicago/Turabian StyleKenneth Lundstrom. 2020. "The Current Status of COVID-19 Vaccines." Frontiers in Genome Editing 2, no. : 1.
The global public health is endangered due to COVID-19 pandemic, which is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Despite having similar pathology to MERS and SARS-CoV, the infection fatality rate of SARS-CoV-2 is likely lower than 1%. SARS-CoV-2 has been reported to be uniquely characterized by the accessory protein ORF10, which contains eleven cytotoxic T lymphocyte (CTL) epitopes of nine amino acids length each, across various human leukocyte antigen (HLA) subtypes. In this study, all missense mutations found in sequence databases were examined across twnety-two unique SARS-CoV-2 ORF10 variants that could possibly alter viral pathogenicity. Some of these mutations decrease the stability of ORF10, e.g. I4L and V6I were found in the MoRF region of ORF10 which may also possibly contribute to Intrinsic protein disorder. Furthermore, a physicochemical and structural comparative analysis was carried out on SARS-CoV-2 and Pangolin-CoV ORF10 proteins, which share 97.37% amino acid homology. The high degree of physicochemical and structural similarity of ORF10 proteins of SARS-CoV-2 and Pangolin-CoV open questions about the architecture of SARS-CoV-2 due to the disagreement of these two ORF10 proteins over their sub-structure (loop/coil region), solubility, antigenicity and change from the strand to coil at amino acid position 26, where tyrosine is present. Altogether, SARS-CoV-2 ORF10 is a promising pharmaceutical target and a protein which should be monitored for changes which correlate to change pathogenesis and clinical course of COVID-19 infection.
Sk. Sarif Hassan; Diksha Attrish; Shinjini Ghosh; Pabitra Pal Choudhury; Vladimir N. Uversky; Bruce D. Uhal; Kenneth Lundstrom; Nima Rezaei; Alaa A. A. Aljabali; Murat Seyran; Damiano Pizzol; Parise Adadi; Tarek Mohamed Abd El-Aziz; Antonio Soares; Ramesh Kandimalla; Murtaza Tambuwala; Amos Lal; Gajendra Kumar Azad; Samendra P. Sherchan; Wagner Baetas-Da-Cruz; Giorgio Palù; Adam M. Brufsky. Notable sequence homology of the ORF10 protein introspects the architecture of SARS-COV-2. 2020, 1 .
AMA StyleSk. Sarif Hassan, Diksha Attrish, Shinjini Ghosh, Pabitra Pal Choudhury, Vladimir N. Uversky, Bruce D. Uhal, Kenneth Lundstrom, Nima Rezaei, Alaa A. A. Aljabali, Murat Seyran, Damiano Pizzol, Parise Adadi, Tarek Mohamed Abd El-Aziz, Antonio Soares, Ramesh Kandimalla, Murtaza Tambuwala, Amos Lal, Gajendra Kumar Azad, Samendra P. Sherchan, Wagner Baetas-Da-Cruz, Giorgio Palù, Adam M. Brufsky. Notable sequence homology of the ORF10 protein introspects the architecture of SARS-COV-2. . 2020; ():1.
Chicago/Turabian StyleSk. Sarif Hassan; Diksha Attrish; Shinjini Ghosh; Pabitra Pal Choudhury; Vladimir N. Uversky; Bruce D. Uhal; Kenneth Lundstrom; Nima Rezaei; Alaa A. A. Aljabali; Murat Seyran; Damiano Pizzol; Parise Adadi; Tarek Mohamed Abd El-Aziz; Antonio Soares; Ramesh Kandimalla; Murtaza Tambuwala; Amos Lal; Gajendra Kumar Azad; Samendra P. Sherchan; Wagner Baetas-Da-Cruz; Giorgio Palù; Adam M. Brufsky. 2020. "Notable sequence homology of the ORF10 protein introspects the architecture of SARS-COV-2." , no. : 1.
Immune evasion is one of the unique characteristics of COVID-19 attributed to the ORF8 protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This protein is involved in modulating the host adaptive immunity through downregulating MHC (Major Histocompatibility Complex) molecules and innate immune responses by surpassing the interferon mediated antiviral response of the host. To understand the immune perspective of the host with respect to the ORF8 protein, a comprehensive study of the ORF8 protein as well as mutations possessed by it, is performed. Chemical and structural properties of ORF8 proteins from different hosts, that is human, bat and pangolin, suggests that the ORF8 of SARS-CoV-2 and Bat RaTG13-CoV are very much closer related than that of Pangolin-CoV. Eighty-seven mutations across unique variants of ORF8 (SARS-CoV-2) are grouped into four classes based on their predicted effects. Based on geolocations and timescale of collection, a possible flow of mutations was built. Furthermore, conclusive flows of amalgamation of mutations were endorsed upon sequence similarity and amino acid conservation phylogenies. Therefore, this study seeks to highlight the uniqueness of rapid evolving SARS-CoV-2 through the ORF8.
Sk. Sarif Hassan; Shinjini Ghosh; Diksha Attrish; Pabirtra Pal Choudhury; Murat Seyran; Damiano Pizzol; Parise Adadi; Tarek Muhammed Abd El Aziz; Antonio Soares; Ramesh Kandimalla; Kenneth Lundstrom; Murtaza Tambuwala; Alaa A. A. Aljabali; Amos Lal; Gajendra Kumar Azad; Vladimir N. Uversky; Samendra P. Sherchan; Wagner Baetas-Da-Cruz; Bruce D. Uhal; Nima Rezaei; Adam M. Brufsky. A unique view of SARS-CoV-2 through the lens of ORF8 protein. 2020, 1 .
AMA StyleSk. Sarif Hassan, Shinjini Ghosh, Diksha Attrish, Pabirtra Pal Choudhury, Murat Seyran, Damiano Pizzol, Parise Adadi, Tarek Muhammed Abd El Aziz, Antonio Soares, Ramesh Kandimalla, Kenneth Lundstrom, Murtaza Tambuwala, Alaa A. A. Aljabali, Amos Lal, Gajendra Kumar Azad, Vladimir N. Uversky, Samendra P. Sherchan, Wagner Baetas-Da-Cruz, Bruce D. Uhal, Nima Rezaei, Adam M. Brufsky. A unique view of SARS-CoV-2 through the lens of ORF8 protein. . 2020; ():1.
Chicago/Turabian StyleSk. Sarif Hassan; Shinjini Ghosh; Diksha Attrish; Pabirtra Pal Choudhury; Murat Seyran; Damiano Pizzol; Parise Adadi; Tarek Muhammed Abd El Aziz; Antonio Soares; Ramesh Kandimalla; Kenneth Lundstrom; Murtaza Tambuwala; Alaa A. A. Aljabali; Amos Lal; Gajendra Kumar Azad; Vladimir N. Uversky; Samendra P. Sherchan; Wagner Baetas-Da-Cruz; Bruce D. Uhal; Nima Rezaei; Adam M. Brufsky. 2020. "A unique view of SARS-CoV-2 through the lens of ORF8 protein." , no. : 1.
RNA interference (RNAi) provides the means for alternative antiviral therapy. Delivery of RNAi in the form of short interfering RNA (siRNA), short hairpin RNA (shRNA) and micro-RNA (miRNA) have demonstrated efficacy in gene silencing for therapeutic applications against viral diseases. Bioinformatics has played an important role in the design of efficient RNAi sequences targeting various pathogenic viruses. However, stability and delivery of RNAi molecules have presented serious obstacles for reaching therapeutic efficacy. For this reason, RNA modifications and formulation of nanoparticles have proven useful for non-viral delivery of RNAi molecules. On the other hand, utilization of viral vectors and particularly self-replicating RNA virus vectors can be considered as an attractive alternative. In this review, examples of antiviral therapy applying RNAi-based approaches in various animal models will be described. Due to the current coronavirus pandemic, a special emphasis will be dedicated to targeting Coronavirus Disease-19 (COVID-19).
Kenneth Lundstrom. Viral Vectors Applied for RNAi-Based Antiviral Therapy. Viruses 2020, 12, 924 .
AMA StyleKenneth Lundstrom. Viral Vectors Applied for RNAi-Based Antiviral Therapy. Viruses. 2020; 12 (9):924.
Chicago/Turabian StyleKenneth Lundstrom. 2020. "Viral Vectors Applied for RNAi-Based Antiviral Therapy." Viruses 12, no. 9: 924.
Alphavirus vectors have been engineered for high-level gene expression relying originally on replication-deficient recombinant particles, more recently designed for plasmid DNA-based administration. As alphavirus-based DNA vectors encode the alphavirus RNA replicon genes, enhanced transgene expression in comparison to conventional DNA plasmids is achieved. Immunization studies with alphavirus-based DNA plasmids have elicited specific antibody production, have generated tumor regression and protection against challenges with infectious agents and tumor cells in various animal models. A limited number of clinical trials have been conducted with alphavirus DNA vectors. Compared to conventional plasmid DNA-based immunization, alphavirus DNA vectors required 1000-fold less DNA to elicit similar immune responses in rodents.
Kenneth Lundstrom. Impact of a Plasmid DNA-Based Alphavirus Vaccine on Immunization Efficiency. Methods in Molecular Biology 2020, 33 -47.
AMA StyleKenneth Lundstrom. Impact of a Plasmid DNA-Based Alphavirus Vaccine on Immunization Efficiency. Methods in Molecular Biology. 2020; ():33-47.
Chicago/Turabian StyleKenneth Lundstrom. 2020. "Impact of a Plasmid DNA-Based Alphavirus Vaccine on Immunization Efficiency." Methods in Molecular Biology , no. : 33-47.
Single-stranded RNA viruses such as alphaviruses, flaviviruses, measles viruses and rhabdoviruses are characterized by their capacity of highly efficient self-amplification of RNA in host cells, which make them attractive vehicles for vaccine development. Particularly, alphaviruses and flaviviruses can be administered as recombinant particles, layered DNA/RNA plasmid vectors carrying the RNA replicon and even RNA replicon molecules. Self-amplifying RNA viral vectors have been used for high level expression of viral and tumor antigens, which in immunization studies have elicited strong cellular and humoral immune responses in animal models. Vaccination has provided protection against challenges with lethal doses of viral pathogens and tumor cells. Moreover, clinical trials have demonstrated safe application of RNA viral vectors and even promising results in rhabdovirus-based phase III trials on an Ebola virus vaccine. Preclinical and clinical applications of self-amplifying RNA viral vectors have proven efficient for vaccine development and due to the presence of RNA replicons, amplification of RNA in host cells will generate superior immune responses with significantly reduced amounts of RNA delivered. The need for novel and efficient vaccines has become even more evident due to the global COVID-19 pandemic, which has further highlighted the urgency in challenging emerging diseases.
Kenneth Lundstrom. Self-Amplifying RNA Viruses as RNA Vaccines. International Journal of Molecular Sciences 2020, 21, 5130 .
AMA StyleKenneth Lundstrom. Self-Amplifying RNA Viruses as RNA Vaccines. International Journal of Molecular Sciences. 2020; 21 (14):5130.
Chicago/Turabian StyleKenneth Lundstrom. 2020. "Self-Amplifying RNA Viruses as RNA Vaccines." International Journal of Molecular Sciences 21, no. 14: 5130.
The current coronavirus COVID-19 pandemic, which originated in Wuhan, China, has raised significant social, psychological and economic concerns in addition to direct medical issues. The rapid spread of severe acute respiratory syndrome-coronavirus (SARS-CoV)-2 to almost every country on the globe and the failure to contain the infections have contributed to fear and panic worldwide. The lack of available and efficient antiviral drugs or vaccines has further worsened the situation. For these reasons, it cannot be overstated that an accelerated effort for the development of novel drugs and vaccines is needed. In this context, novel approaches in both gene therapy and vaccine development are essential. Previous experience from SARS- and MERS-coronavirus vaccine and drug development projects have targeted glycoprotein epitopes, monoclonal antibodies, angiotensin receptor blockers and gene silencing technologies, which may be useful for COVID-19 too. Moreover, existing antivirals used for other types of viral infections have been considered as urgent action is necessary. This review aims at providing a background of coronavirus genetics and biology, examples of therapeutic and vaccine strategies taken and potential innovative novel approaches in progress.
Kenneth Lundstrom. Coronavirus Pandemic—Therapy and Vaccines. Biomedicines 2020, 8, 109 .
AMA StyleKenneth Lundstrom. Coronavirus Pandemic—Therapy and Vaccines. Biomedicines. 2020; 8 (5):109.
Chicago/Turabian StyleKenneth Lundstrom. 2020. "Coronavirus Pandemic—Therapy and Vaccines." Biomedicines 8, no. 5: 109.