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Bruce D. Uhal PhD is Professor of Physiology in the College of Human Medicine at Michigan State University. He has previously been on the faculties of the University of Illinois at Chicago (Dept. Medicine), Rush Medical College (Dept. Pharmacology), Pennsylvania State University Medical School (Hershey, Dept. Cell and Molecular Physiology) and was Director for Research of The Cardiovascular Institute, Michael Reese Hospital, Chicago IL from 1997-2000. Dr. Uhal is an expert on the regulation of lung alveolar epithelial cell proliferation and death, a topic that he has been continuously funded by the NIH to study since 1990. His work has focused on the regulation of alveolar epithelial cell (AEC) death by apoptosis specifically in the context of lung fibrosis. Major discoveries include the finding that a local tissue (extravascular) angiotensin system is activated in and required for the pathogenesis of both experimental lung fibrosis in animals and human lung fibrosis. More recently, his laboratory found that the inhibitory axis of this system, the ACE-2/ANG1-7/MAS axis, controls AEC survival by regulating the rate of apoptosis in response to a wide variety of xenobiotic, endogenous and/or genetic stimuli that are involved in the pathogenesis of human lung fibrosis.
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.
Several hypotheses have been presented on the origin of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from its identification as the agent causing the current coronavirus disease 19 (COVID-19) pandemic. So far, no hypothesis has managed to identify the origin, and the issue has resurfaced. Here we have unfolded a pattern of distribution of several mutations in the SARS-CoV-2 proteins across different continents comprising 24 geo-locations. The results showed an evenly uneven distribution of unique protein variants, distinct mutations, unique frequency of common conserved residues, and mutational residues across the 24 geo-locations. Furthermore, ample mutations were identified in the evolutionarily conserved invariant regions in the SARS-CoV-2 proteins across almost all geo-locations we have considered. This pattern of mutations potentially breaches the law of evolutionary conserved functional units of the beta-coronavirus genus. These mutations may lead to several novel SARS-CoV-2 variants with a high degree of transmissibility and virulence. A thorough investigation on the origin and characteristics of SARS-CoV-2 needs to be conducted in the interest of science and to be prepared to meet the challenges of potential future pandemics.
Sk Sarif Hassan; Vaishnavi Kodakandla; Elrashdy M. Redwan; Kenneth Lundstrom; Pabitra Pal Choudhury; Ángel Serrano-Aroca Aroca; Gajendra Kumar Azad; Alaa A.A. Aljabali; Giorgio Palu; Tarek Mohamed Abd El-Aziz; Debmalya Barh; Bruce D. Uhal; Parise Adadi; Kazuo Takayama; Nicolas G. Bazan; Murtaza Tambuwala; Samendra P. Sherchan; Amos Lal; Gaurav Chauhan; Wagner Baetas-Da-Cruz; Vladimir N. Uversky. Non-Uniform Aspects of SARS-CoV-2 Intraspecies Evolution Reopen Questions on Its Origin. 2021, 1 .
AMA StyleSk Sarif Hassan, Vaishnavi Kodakandla, Elrashdy M. Redwan, Kenneth Lundstrom, Pabitra Pal Choudhury, Ángel Serrano-Aroca Aroca, Gajendra Kumar Azad, Alaa A.A. Aljabali, Giorgio Palu, Tarek Mohamed Abd El-Aziz, Debmalya Barh, Bruce D. Uhal, Parise Adadi, Kazuo Takayama, Nicolas G. Bazan, Murtaza Tambuwala, Samendra P. Sherchan, Amos Lal, Gaurav Chauhan, Wagner Baetas-Da-Cruz, Vladimir N. Uversky. Non-Uniform Aspects of SARS-CoV-2 Intraspecies Evolution Reopen Questions on Its Origin. . 2021; ():1.
Chicago/Turabian StyleSk Sarif Hassan; Vaishnavi Kodakandla; Elrashdy M. Redwan; Kenneth Lundstrom; Pabitra Pal Choudhury; Ángel Serrano-Aroca Aroca; Gajendra Kumar Azad; Alaa A.A. Aljabali; Giorgio Palu; Tarek Mohamed Abd El-Aziz; Debmalya Barh; Bruce D. Uhal; Parise Adadi; Kazuo Takayama; Nicolas G. Bazan; Murtaza Tambuwala; Samendra P. Sherchan; Amos Lal; Gaurav Chauhan; Wagner Baetas-Da-Cruz; Vladimir N. Uversky. 2021. "Non-Uniform Aspects of SARS-CoV-2 Intraspecies Evolution Reopen Questions on Its Origin." , no. : 1.
The COVID-19 pandemic caused by the coronavirus SARS-COV-2 has cost many lives worldwide. In dealing with affected patients, the physician is faced with a very unusual pattern of organ damage that is not easily explained on the basis of prior knowledge of viral-induced pathogenesis. It is established that the main receptor for viral entry into tissues is the protein angiotensin-converting enzyme-2 [“ACE-2”, (1)]. In a recent publication (2), a theory of autoimmunity against ACE-2, and/or against the ACE-2/SARS-COV-2 spike protein complex or degradation products thereof, was proposed as a possible explanation for the unusual pattern of organ damage seen in COVID-19. In the light of more recent information, this manuscript expands on the earlier proposed theory and offers additional, testable hypotheses that could explain both the pattern and timeline of organ dysfunction most often observed in COVID-19.
Philip McMillan; Thomas Dexhiemer; Richard R. Neubig; Bruce D. Uhal. COVID-19—A Theory of Autoimmunity Against ACE-2 Explained. Frontiers in Immunology 2021, 12, 582166 .
AMA StylePhilip McMillan, Thomas Dexhiemer, Richard R. Neubig, Bruce D. Uhal. COVID-19—A Theory of Autoimmunity Against ACE-2 Explained. Frontiers in Immunology. 2021; 12 ():582166.
Chicago/Turabian StylePhilip McMillan; Thomas Dexhiemer; Richard R. Neubig; Bruce D. Uhal. 2021. "COVID-19—A Theory of Autoimmunity Against ACE-2 Explained." Frontiers in Immunology 12, no. : 582166.
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.
Therapeutic options for the highly pathogenic human Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) causing the current pandemic Coronavirus disease (COVID-19) are urgently needed. COVID-19 is associated with viral pneumonia and acute respiratory distress syndrome causing significant morbidity and mortality. The proposed treatments for COVID-19, such as hydroxychloroquine, remdesivir and lopinavir/ritonavir, have shown little or no effect in the clinic. Additionally, bacterial and fungal pathogens contribute to the SARS-CoV-2 mediated pneumonia disease complex. The antibiotic resistance in pneumonia treatment is increasing at an alarming rate. Therefore, carbon-based nanomaterials (CBNs), such as fullerene, carbon dots, graphene, and their derivatives constitute a promising alternative due to their wide-spectrum antimicrobial activity, biocompatibility, biodegradability and capacity to induce tissue regeneration. Furthermore, the antimicrobial mode of action is mainly physical (e.g. membrane distortion), which is characterized by a low risk of antimicrobial resistance. In this review, we evaluated the literature on the antiviral activity and broad-spectrum antimicrobial properties of CBNs. CBNs had antiviral activity against 12 enveloped positive-sense single-stranded RNA viruses similar to SARS-CoV-2. CBNs with low or no toxicity to the humans are promising therapeutics against COVID-19 pneumonia complex with other viruses, bacteria and fungi, including those that are multidrug-resistant.
Ángel Serrano-Aroca; Kazuo Takayama; Alberto Tuñón-Molina; Murat Seyran; Sk. Sarif Hassan; Pabitra Pal Choudhury; Vladimir N. Uversky; Kenneth Lundstrom; Parise Adadi; Giorgio Palù; Alaa A. A. Aljabali; Gaurav Chauhan; Ramesh Kandimalla; Murtaza M. Tambuwala; Amos Lal; Bruce D. Uhal; Adam M. Brufsky. Carbon-Based Nanomaterials: Promising Antiviral Agents to Combat COVID-19 in the Microbial Resistant Era. 2021, 1 .
AMA StyleÁngel Serrano-Aroca, Kazuo Takayama, Alberto Tuñón-Molina, Murat Seyran, Sk. Sarif Hassan, Pabitra Pal Choudhury, Vladimir N. Uversky, Kenneth Lundstrom, Parise Adadi, Giorgio Palù, Alaa A. A. Aljabali, Gaurav Chauhan, Ramesh Kandimalla, Murtaza M. Tambuwala, Amos Lal, Bruce D. Uhal, Adam M. Brufsky. Carbon-Based Nanomaterials: Promising Antiviral Agents to Combat COVID-19 in the Microbial Resistant Era. . 2021; ():1.
Chicago/Turabian StyleÁngel Serrano-Aroca; Kazuo Takayama; Alberto Tuñón-Molina; Murat Seyran; Sk. Sarif Hassan; Pabitra Pal Choudhury; Vladimir N. Uversky; Kenneth Lundstrom; Parise Adadi; Giorgio Palù; Alaa A. A. Aljabali; Gaurav Chauhan; Ramesh Kandimalla; Murtaza M. Tambuwala; Amos Lal; Bruce D. Uhal; Adam M. Brufsky. 2021. "Carbon-Based Nanomaterials: Promising Antiviral Agents to Combat COVID-19 in the Microbial Resistant Era." , no. : 1.
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.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) is the causative agent of the pandemic coronavirus disease 2019 (COVID‐19) that exhibits an overwhelming contagious capacity over other Human Coronaviruses (HCoVs). This structural snapshot describes the structural bases underlying the pandemic capacity of SARS‐CoV‐2 and explains its fast motion over respiratory epithelia that allow its rapid cellular entry. Based on notable viral spike (S) protein features, we propose that the flat sialic acid‐binding domain at the N‐terminal domain (NTD) of the S1 subunit leads to more effective first contact and interaction with the sialic acid layer over the epithelium and this, in turn, allows faster viral "surfing" of the epithelium and receptor scanning by SARS‐CoV‐2. Angiotensin‐converting enzyme 2 (ACE‐2) protein on the epithelial surface is the primary entry receptor for SARS‐CoV‐2, and protein‐protein interaction assays demonstrate high‐affinity binding of the S protein to ACE‐2. To date, no high‐frequency mutations were detected at the C‐terminal domain (CTD) of the S1 subunit in the S protein, where the receptor‐binding domain (RBD) is located. Tight binding to ACE‐2 by a conserved viral RBD suggests the ACE2‐RBD interaction is likely optimal. Moreover, the viral S subunit contains a cleavage site for furin and other proteases, which accelerates cell entry by SARS‐CoV‐2. The model proposed here describes a structural basis for the accelerated host cell entry by SARS‐CoV‐2 relative to other HCoVs, and also discusses emerging hypotheses that are likely to contribute to the development of antiviral strategies to combat the pandemic capacity of SARS‐CoV‐2.
Murat Seyran; Kazuo Takayama; Vladimir N. Uversky; Kenneth Lundstrom; Giorgio Palù; Samendra P. Sherchan; Diksha Attrish; Nima Rezaei; Alaa A. A. Aljabali; Shinjini Ghosh; Damiano Pizzol; Gaurav Chauhan; Parise Adadi; Tarek Mohamed Abd El‐Aziz; Antonio G. Soares; Ramesh Kandimalla; Murtaza Tambuwala; Sk. Sarif Hassan; Gajendra Kumar Azad; Pabitra Pal Choudhury; Wagner Baetas‐Da‐Cruz; Ángel Serrano‐Aroca; Adam M. Brufsky; Bruce D. Uhal. The structural basis of accelerated host cell entry by SARS‐CoV‐2†. The FEBS Journal 2020, 1 .
AMA StyleMurat Seyran, Kazuo Takayama, Vladimir N. Uversky, Kenneth Lundstrom, Giorgio Palù, Samendra P. Sherchan, Diksha Attrish, Nima Rezaei, Alaa A. A. Aljabali, Shinjini Ghosh, Damiano Pizzol, Gaurav Chauhan, Parise Adadi, Tarek Mohamed Abd El‐Aziz, Antonio G. Soares, Ramesh Kandimalla, Murtaza Tambuwala, Sk. Sarif Hassan, Gajendra Kumar Azad, Pabitra Pal Choudhury, Wagner Baetas‐Da‐Cruz, Ángel Serrano‐Aroca, Adam M. Brufsky, Bruce D. Uhal. The structural basis of accelerated host cell entry by SARS‐CoV‐2†. The FEBS Journal. 2020; ():1.
Chicago/Turabian StyleMurat Seyran; Kazuo Takayama; Vladimir N. Uversky; Kenneth Lundstrom; Giorgio Palù; Samendra P. Sherchan; Diksha Attrish; Nima Rezaei; Alaa A. A. Aljabali; Shinjini Ghosh; Damiano Pizzol; Gaurav Chauhan; Parise Adadi; Tarek Mohamed Abd El‐Aziz; Antonio G. Soares; Ramesh Kandimalla; Murtaza Tambuwala; Sk. Sarif Hassan; Gajendra Kumar Azad; Pabitra Pal Choudhury; Wagner Baetas‐Da‐Cruz; Ángel Serrano‐Aroca; Adam M. Brufsky; Bruce D. Uhal. 2020. "The structural basis of accelerated host cell entry by SARS‐CoV‐2†." The FEBS Journal , no. : 1.
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.
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.
Philip McMillan; Bruce D. Uhal. COVID-19–A theory of autoimmunity to ACE-2. 2020, 7, 17 -19.
AMA StylePhilip McMillan, Bruce D. Uhal. COVID-19–A theory of autoimmunity to ACE-2. . 2020; 7 (1):17-19.
Chicago/Turabian StylePhilip McMillan; Bruce D. Uhal. 2020. "COVID-19–A theory of autoimmunity to ACE-2." 7, no. 1: 17-19.
BackgroundHypersensitivity Pneumonitis (HP) is an interstitial lung disease caused by an immune response to the inhalation of antigens. Since only a small proportion of individuals exposed to HP-related antigens develop the disease, a genetic variation may play a role in disease development.MethodsIn this small-scale study, 24 patients diagnosed with HP were matched with control group who shared the patient’s environment and were exposed to the same HP-associated antigens. Logistic regression was employed to identify Single-Nucleotide Polymorphisms (SNPs) associated with HP. Next genes associated with HP were identified using sequence kernel association test (SKAT) analysis. Last, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Oncology (GO) enrichment analysis were employed to find HP signaling pathways using SNPs coded on genes and on non-coding genes, respectively.ResultsGiven the small sample size, no single SNPs or genes were identified to be significantly associated with HP after adjustment for multiple testing. After P-value adjustment, the KEGG and GO pathway enrichment analysis identified 11 and 20 significant pathways respectively using SNPs coded on genes. Among these pathways, Cell cycle, Proteasome and Base excision repair had previously reported to be associated with lung function.ConclusionThis is the first GWAS study identifying genetic factors associated with HP. Although no significant associations at SNPs/gene level were identified, there were significant pathways that are identified associated with HP which need further investigation in large cohorts.
Ling Wang; Melissa May Millerick; Kenneth D. Rosenman; Yuehua Cui; Bruce Uhal; Jianrong Wang; John Gerlach. Using Genome-Wide Association Study to Identify Genes and Pathways associated with Hypersensitivity Pneumonitis. 2020, 1 .
AMA StyleLing Wang, Melissa May Millerick, Kenneth D. Rosenman, Yuehua Cui, Bruce Uhal, Jianrong Wang, John Gerlach. Using Genome-Wide Association Study to Identify Genes and Pathways associated with Hypersensitivity Pneumonitis. . 2020; ():1.
Chicago/Turabian StyleLing Wang; Melissa May Millerick; Kenneth D. Rosenman; Yuehua Cui; Bruce Uhal; Jianrong Wang; John Gerlach. 2020. "Using Genome-Wide Association Study to Identify Genes and Pathways associated with Hypersensitivity Pneumonitis." , no. : 1.
Background: Neonatal therapy with a high concentration of oxygen (hyperoxia) is a known cause of bronchopulmonary dysplasia (BPD). BPD is characterized by increased pulmonary permeability and diffuse infiltration of various inflammatory cells. Disruption of the epithelial barrier may lead to altered pulmonary permeability and airways fluid accumulation. Mas receptor is a component of the renin angiotensin system and is the receptor for the protective endogenous peptide angiotensin 1-7. The activation of the Mas receptor was previously shown to have protective pulmonary responses. However, the effect of Mas receptor activation on epithelial barrier integrity has not been tested. Objective: To determine the effects of hyperoxia with or without Mas receptor activation on epithelial cell barrier integrity. Design/Methods: Human epithelial cell line A549 was cultured on transwell polycarbonate porous membrane to confluence and treated with 95% oxygen (hyperoxia) for 72 hours with or without the Mas receptor agonist (AVE0991), or the apoptotic inhibitors Z-VAD-FMK or aurintricarboxylic acid. The cells were then challenged with Rhodamine labeled bovine serum albumin (Rh-BSA) on one side of the membrane. Fluorescent quantitation of Rh-BSA (albumin flux) was performed on the media in the other side of the membrane 3 hours later and was compared with 21% oxygen (Normoxia) control group. A549 cells were also cultured with or without AVE0991 in hyperoxia or normoxia and used for nuclear fragmentation apoptosis assay using propidium iodide staining. Results: Hyperoxia induced an increase in albumin flux that was significantly prevented by AVE0991 treatment and by the apoptosis inhibitors. AVE0991 also significantly decreased the hyperoxia-induced nuclear fragmentation. Conclusion: These results suggest that hyperoxia causes a disruption in the epithelial barrier integrity, and that this disruption is inhibited by the Mas receptor agonist AVE0991 through inhibition of epithelial apoptosis. These results reveal a novel potential drug for BPD and pulmonary edema treatment.
Amal Abdul-Hafez; Tarek Mohamed; Bruce D Uhal. Activation of mas restores hyperoxia-induced loss of lung epithelial barrier function through inhibition of apoptosis. Journal of Lung, Pulmonary & Respiratory Research 2019, 6, 58 -62.
AMA StyleAmal Abdul-Hafez, Tarek Mohamed, Bruce D Uhal. Activation of mas restores hyperoxia-induced loss of lung epithelial barrier function through inhibition of apoptosis. Journal of Lung, Pulmonary & Respiratory Research. 2019; 6 (3):58-62.
Chicago/Turabian StyleAmal Abdul-Hafez; Tarek Mohamed; Bruce D Uhal. 2019. "Activation of mas restores hyperoxia-induced loss of lung epithelial barrier function through inhibition of apoptosis." Journal of Lung, Pulmonary & Respiratory Research 6, no. 3: 58-62.