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The focus of my research is to understand the molecular mechanisms that govern the regulation of ion channels and cell surface receptors in physiological and pathological states. Our understanding of their function is critical for the development of therapeutic approaches aimed at treating and preventing channelopathies, human diseases related to the dysfunction of ion channels. Experimental approaches that I commonly use to study ion channels include electrophysiology, structural biology, cell biology, biochemistry, and animal models. My research scope is multidisciplinary in nature and I am interesting in understanding from the molecule to the whole animal.
Cerebral ischemia-reperfusion (I-R) transiently increased autophagy by producing excessively reactive oxygen species (ROS); on the other hand, activated autophagy would remove ROS-damaged mitochondria and proteins, which led to cell survival. However, the regulation mechanism of autophagy activity during cerebral I-R is still unclear. In this study, we found that deficiency of the TRPM2 channel which is a ROS sensor significantly decreased I-R-induced neuronal damage. I-R transiently increased autophagy activity both in vitro and in vivo. More importantly, TRPM2 deficiency decreased I-R-induced neurological deficit score and infarct volume. Interestingly, our results indicated that TRPM2 deficiency could further activate AMPK rather than Beclin1 activity, suggesting that TRPM2 inhibits autophagy by regulating the AMPK/mTOR pathway in I-R. In conclusion, our study reveals that ROS-activated TRPM2 inhibits autophagy by downregulating the AMPK/mTOR pathway, which results in neuronal death induced by cerebral I-R, further supporting that TRPM2 might be a potential drug target for cerebral ischemic injury therapy.
Xupang Hu; Lijuan Wu; Xingyu Liu; Yi Zhang; Min Xu; Qiuyuan Fang; Lin Lu; Jianguo Niu; Tarek Mohamed Abd El-Aziz; Lin-Hua Jiang; Fangfang Li; Wei Yang. Deficiency of ROS-Activated TRPM2 Channel Protects Neurons from Cerebral Ischemia-Reperfusion Injury through Upregulating Autophagy. Oxidative Medicine and Cellular Longevity 2021, 2021, 1 -12.
AMA StyleXupang Hu, Lijuan Wu, Xingyu Liu, Yi Zhang, Min Xu, Qiuyuan Fang, Lin Lu, Jianguo Niu, Tarek Mohamed Abd El-Aziz, Lin-Hua Jiang, Fangfang Li, Wei Yang. Deficiency of ROS-Activated TRPM2 Channel Protects Neurons from Cerebral Ischemia-Reperfusion Injury through Upregulating Autophagy. Oxidative Medicine and Cellular Longevity. 2021; 2021 ():1-12.
Chicago/Turabian StyleXupang Hu; Lijuan Wu; Xingyu Liu; Yi Zhang; Min Xu; Qiuyuan Fang; Lin Lu; Jianguo Niu; Tarek Mohamed Abd El-Aziz; Lin-Hua Jiang; Fangfang Li; Wei Yang. 2021. "Deficiency of ROS-Activated TRPM2 Channel Protects Neurons from Cerebral Ischemia-Reperfusion Injury through Upregulating Autophagy." Oxidative Medicine and Cellular Longevity 2021, no. : 1-12.
The devastating impact of the ongoing coronavirus disease 2019 (COVID-19) on public health, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has made fighting of the COVID-19 pandemic is a top priority in medical research and pharmaceutical development. Surveillance of SARS-CoV-2 mutations is essential for the comprehension of SARS-CoV-2 variant diversity and their impact on virulence and pathogenicity. The SARS-CoV-2 open reading frame 10 (ORF10) protein interacts with multiple human proteins CUL2, ELOB, ELOC, MAP7D1, PPT1, RBX1, THTPA, TIMM8B, and ZYG11B expressed in the lung tissues. Mutations and co-mutations in the emerging SARS-CoV-2 ORF10 variants are expected to impact the severity of the virus and its associated consequences. In this article, We highlight 128 single mutations and 35 co-mutations in the unique SARS-CoV-2 ORF10 variants in this article. The possible predicted effects of these mutations and co-mutations on the secondary structure of ORF10 variants and host protein interactomes are presented. The findings highlight the possible effects of mutations and co-mutations on the emerging 140 ORF10 unique variants from secondary structure and intrinsic protein disorder perspectives.
Sk. Sarif Hassan; Kenneth Lundstrom; Ángel Serrano-Aroca; Parise Adadi; Alaa Aljabali; ElRashdy Redwan; Amos Lal; Ramesh Kandimalla; Tarek El-Aziz; Pabitra Choudhury; Gajendra Azad; Samendra Sherchan; Murtaza Tambuwala; Gaurav Chauhan; Kazuo Takayama; Debmalya Barh; Giorgio Palù; Pallab Basu; Vladimir N Uversky. Emergence of Unique SARS-CoV-2 ORF10 Variants and Their Impact on Protein Structure and Function. 2021, 1 .
AMA StyleSk. Sarif Hassan, Kenneth Lundstrom, Ángel Serrano-Aroca, Parise Adadi, Alaa Aljabali, ElRashdy Redwan, Amos Lal, Ramesh Kandimalla, Tarek El-Aziz, Pabitra Choudhury, Gajendra Azad, Samendra Sherchan, Murtaza Tambuwala, Gaurav Chauhan, Kazuo Takayama, Debmalya Barh, Giorgio Palù, Pallab Basu, Vladimir N Uversky. Emergence of Unique SARS-CoV-2 ORF10 Variants and Their Impact on Protein Structure and Function. . 2021; ():1.
Chicago/Turabian StyleSk. Sarif Hassan; Kenneth Lundstrom; Ángel Serrano-Aroca; Parise Adadi; Alaa Aljabali; ElRashdy Redwan; Amos Lal; Ramesh Kandimalla; Tarek El-Aziz; Pabitra Choudhury; Gajendra Azad; Samendra Sherchan; Murtaza Tambuwala; Gaurav Chauhan; Kazuo Takayama; Debmalya Barh; Giorgio Palù; Pallab Basu; Vladimir N Uversky. 2021. "Emergence of Unique SARS-CoV-2 ORF10 Variants and Their Impact on Protein Structure and Function." , no. : 1.
The voltage-gated sodium channel Nav1.8 is linked to neuropathic and inflammatory pain, highlighting the potential to serve as a drug target. However, the biophysical mechanisms that regulate Nav1.8 activation and inactivation gating are not completely understood. Progress has been hindered by a lack of biochemical tools for examining Nav1.8 gating mechanisms. Arizona bark scorpion (Centruroides sculpturatus) venom proteins inhibit Nav1.8 and block pain in grasshopper mice (Onychomys torridus). These proteins provide tools for examining Nav1.8 structure–activity relationships. To identify proteins that inhibit Nav1.8 activity, venom samples were fractioned using liquid chromatography (reversed-phase and ion exchange). A recombinant Nav1.8 clone expressed in ND7/23 cells was used to identify subfractions that inhibited Nav1.8 Na+ current. Mass-spectrometry-based bottom-up proteomic analyses identified unique peptides from inhibitory subfractions. A search of the peptides against the AZ bark scorpion venom gland transcriptome revealed four novel proteins between 40 and 60% conserved with venom proteins from scorpions in four genera (Centruroides, Parabuthus, Androctonus, and Tityus). Ranging from 63 to 82 amino acids, each primary structure includes eight cysteines and a “CXCE” motif, where X = an aromatic residue (tryptophan, tyrosine, or phenylalanine). Electrophysiology data demonstrated that the inhibitory effects of bioactive subfractions can be removed by hyperpolarizing the channels, suggesting that proteins may function as gating modifiers as opposed to pore blockers.
Tarek Abd El-Aziz; Yucheng Xiao; Jake Kline; Harold Gridley; Alyse Heaston; Klaus Linse; Micaiah Ward; Darin Rokyta; James Stockand; Theodore Cummins; Luca Fornelli; Ashlee Rowe. Identification and Characterization of Novel Proteins from Arizona Bark Scorpion Venom That Inhibit Nav1.8, a Voltage-Gated Sodium Channel Regulator of Pain Signaling. Toxins 2021, 13, 501 .
AMA StyleTarek Abd El-Aziz, Yucheng Xiao, Jake Kline, Harold Gridley, Alyse Heaston, Klaus Linse, Micaiah Ward, Darin Rokyta, James Stockand, Theodore Cummins, Luca Fornelli, Ashlee Rowe. Identification and Characterization of Novel Proteins from Arizona Bark Scorpion Venom That Inhibit Nav1.8, a Voltage-Gated Sodium Channel Regulator of Pain Signaling. Toxins. 2021; 13 (7):501.
Chicago/Turabian StyleTarek Abd El-Aziz; Yucheng Xiao; Jake Kline; Harold Gridley; Alyse Heaston; Klaus Linse; Micaiah Ward; Darin Rokyta; James Stockand; Theodore Cummins; Luca Fornelli; Ashlee Rowe. 2021. "Identification and Characterization of Novel Proteins from Arizona Bark Scorpion Venom That Inhibit Nav1.8, a Voltage-Gated Sodium Channel Regulator of Pain Signaling." Toxins 13, no. 7: 501.
Elrashdy M. Redwan; Mohammed F. Alghamdi; Tarek Mohamed Abd El-Aziz; Parise Adadi; Alaa A.A. Aljabali; Diksha Attrish; Gajendra Kumar Azad; Wagner Baetas-Da-Cruz; Debmalya Barh; Nicolas G. Bazan; Adam M. Brufsky; Gaurav Chauhan; S.K. Sarif Hassan; Ramesh Kandimalla; Amos Lal; Kenneth Lundstrom; Yogendra Kumar Mishra; Pabitra Pal Choudhury; Giorgio Palù; Pritam K. Panda; Damiano Pizzol; Nima Rezaei; Ángel Serrano-Aroca; Samendra P. Sherchan; Murat Seyran; Kazuo Takayama; Murtaza M. Tambuwala; Bruce D. Uhal; Vladimir N. Uversky. The mechanism behind flaring/triggering of autoimmunity disorders associated with COVID-19. Autoimmunity Reviews 2021, 20, 102909 -102909.
AMA StyleElrashdy M. Redwan, Mohammed F. Alghamdi, Tarek Mohamed Abd El-Aziz, Parise Adadi, Alaa A.A. Aljabali, Diksha Attrish, Gajendra Kumar Azad, Wagner Baetas-Da-Cruz, Debmalya Barh, Nicolas G. Bazan, Adam M. Brufsky, Gaurav Chauhan, S.K. Sarif Hassan, Ramesh Kandimalla, Amos Lal, Kenneth Lundstrom, Yogendra Kumar Mishra, Pabitra Pal Choudhury, Giorgio Palù, Pritam K. Panda, Damiano Pizzol, Nima Rezaei, Ángel Serrano-Aroca, Samendra P. Sherchan, Murat Seyran, Kazuo Takayama, Murtaza M. Tambuwala, Bruce D. Uhal, Vladimir N. Uversky. The mechanism behind flaring/triggering of autoimmunity disorders associated with COVID-19. Autoimmunity Reviews. 2021; 20 (10):102909-102909.
Chicago/Turabian StyleElrashdy M. Redwan; Mohammed F. Alghamdi; Tarek Mohamed Abd El-Aziz; Parise Adadi; Alaa A.A. Aljabali; Diksha Attrish; Gajendra Kumar Azad; Wagner Baetas-Da-Cruz; Debmalya Barh; Nicolas G. Bazan; Adam M. Brufsky; Gaurav Chauhan; S.K. Sarif Hassan; Ramesh Kandimalla; Amos Lal; Kenneth Lundstrom; Yogendra Kumar Mishra; Pabitra Pal Choudhury; Giorgio Palù; Pritam K. Panda; Damiano Pizzol; Nima Rezaei; Ángel Serrano-Aroca; Samendra P. Sherchan; Murat Seyran; Kazuo Takayama; Murtaza M. Tambuwala; Bruce D. Uhal; Vladimir N. Uversky. 2021. "The mechanism behind flaring/triggering of autoimmunity disorders associated with COVID-19." Autoimmunity Reviews 20, no. 10: 102909-102909.
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.
A global strategy, under the coordination of the World Health Organization, is being unfolded to reduce the impact of snakebite envenoming. One of the pillars of this strategy is to ensure safe and effective treatments. The mainstay in the therapy of snakebite envenoming is the administration of animal-derived antivenoms. In addition, new therapeutic options are being explored, including recombinant antibodies and natural and synthetic toxin inhibitors. In this review, snake venom toxins are classified in terms of their abundance and toxicity, and priority actions are being proposed in the search for snake venom metalloproteinase (SVMP), phospholipase A2 (PLA2), three-finger toxin (3FTx), and serine proteinase (SVSP) inhibitors. Natural inhibitors include compounds isolated from plants, animal sera, and mast cells, whereas synthetic inhibitors comprise a wide range of molecules of a variable chemical nature. Some of the most promising inhibitors, especially SVMP and PLA2 inhibitors, have been developed for other diseases and are being repurposed for snakebite envenoming. In addition, the search for drugs aimed at controlling endogenous processes generated in the course of envenoming is being pursued. The present review summarizes some of the most promising developments in this field and discusses issues that need to be considered for the effective translation of this knowledge to improve therapies for tackling snakebite envenoming.
José Gutiérrez; Laura-Oana Albulescu; Rachel Clare; Nicholas Casewell; Tarek Abd El-Aziz; Teresa Escalante; Alexandra Rucavado. The Search for Natural and Synthetic Inhibitors That Would Complement Antivenoms as Therapeutics for Snakebite Envenoming. Toxins 2021, 13, 451 .
AMA StyleJosé Gutiérrez, Laura-Oana Albulescu, Rachel Clare, Nicholas Casewell, Tarek Abd El-Aziz, Teresa Escalante, Alexandra Rucavado. The Search for Natural and Synthetic Inhibitors That Would Complement Antivenoms as Therapeutics for Snakebite Envenoming. Toxins. 2021; 13 (7):451.
Chicago/Turabian StyleJosé Gutiérrez; Laura-Oana Albulescu; Rachel Clare; Nicholas Casewell; Tarek Abd El-Aziz; Teresa Escalante; Alexandra Rucavado. 2021. "The Search for Natural and Synthetic Inhibitors That Would Complement Antivenoms as Therapeutics for Snakebite Envenoming." Toxins 13, no. 7: 451.
The voltage-gated sodium channel Nav1.8 is linked to neuropathic and inflammatory pain, high-lighting the potential to serve as a drug target. However, the biophysical mechanisms that regu-late Nav1.8 activation and inactivation gating are not completely understood. Progress has been hindered by a lack of biochemical tools for examining Nav1.8 gating mechanisms. Arizona bark scorpion (Centruroides sculpturatus) venom proteins inhibit Nav1.8 and block pain in grasshopper mice (Onychomys torridus). These proteins provide tools for examining Nav1.8 structure-activity relationships. To identify proteins that inhibit Nav1.8 activity, venom samples were fractioned using liquid chromatography (reversed phase and ion exchange). A recombinant Nav1.8 clone expressed in ND7/23 cells was used to identify subfractions that inhibited Nav1.8 Na+ current. Mass spectrometry-based bottom-up proteomic analyses identified unique peptides from inhibi-tory subfractions. A search of the peptides against the AZ bark scorpion venom gland transcrip-tome revealed four novel proteins between 40 and 60% conserved with venom proteins from scorpions in four genera (Centruroides, Parabuthus, Androctonus, and Tityus). Ranging from 63 to 82 amino acids, each primary structure includes 8 cysteines and a CXCE motif where X = an aro-matic residue (tryptophan, tyrosine or phenylalanine). Electrophysiology data demonstrated that the inhibitory effects of bioactive subfractions can be removed by hyperpolarizing the channels, suggesting that proteins may function as gating modifiers as opposed to pore blockers.
Tarek Mohamed Abd El-Aziz; Yucheng Xiao; Jake Kline; Harold Gridley; Alyse Heaston; Klaus D. Linse; Micaiah J. Ward; Darin R. Rokyta; James D. Stockand; Theodore R. Cummins; Luca Fornelli; Ashlee H. Rowe. Identification and characterization of novel proteins from Arizona bark scorpion venom that inhibit Nav1.8, a voltage-gated sodium channel regulator of pain signaling. 2021, 1 .
AMA StyleTarek Mohamed Abd El-Aziz, Yucheng Xiao, Jake Kline, Harold Gridley, Alyse Heaston, Klaus D. Linse, Micaiah J. Ward, Darin R. Rokyta, James D. Stockand, Theodore R. Cummins, Luca Fornelli, Ashlee H. Rowe. Identification and characterization of novel proteins from Arizona bark scorpion venom that inhibit Nav1.8, a voltage-gated sodium channel regulator of pain signaling. . 2021; ():1.
Chicago/Turabian StyleTarek Mohamed Abd El-Aziz; Yucheng Xiao; Jake Kline; Harold Gridley; Alyse Heaston; Klaus D. Linse; Micaiah J. Ward; Darin R. Rokyta; James D. Stockand; Theodore R. Cummins; Luca Fornelli; Ashlee H. Rowe. 2021. "Identification and characterization of novel proteins from Arizona bark scorpion venom that inhibit Nav1.8, a voltage-gated sodium channel regulator of pain signaling." , no. : 1.
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 current Coronavirus Disease 19 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) shows similar pathology to MERS and SARS-CoV, with a current estimated fatality rate of 1.4%. Open reading frame 10 (ORF10) is a unique SARS-CoV-2 accessory protein, which contains eleven cytotoxic T lymphocyte (CTL) epitopes each of nine amino acids in length. Twenty-two unique SARS-CoV-2 ORF10 variants have been identified based on missense mutations found in sequence databases. Some of these mutations are predicted to decrease the stability of ORF10 in silico physicochemical and structural comparative analyses were carried out on SARS-CoV-2 and Pangolin-CoV ORF10 proteins, which share 97.37% amino acid (aa) homology. Though there is a high degree of ORF10 protein similarity of SARS-CoV-2 and Pangolin-CoV, there are differences of these two ORF10 proteins related to their sub-structure (loop/coil region), solubility, antigenicity and shift from strand to coil at aa position 26 (tyrosine). SARS-CoV-2 ORF10, which is apparently expressed in vivo since reactive T cell clones are found in convalescent patients should be monitored for changes which could correlate with the pathogenesis of COVID-19.
Sk. Sarif Hassan; Diksha Attrish; Shinjini Ghosh; Pabitra Pal Choudhury; Vladimir N. Uversky; Alaa A.A. Aljabali; Kenneth Lundstrom; Bruce D. Uhal; Nima Rezaei; 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; Amos Lal; Giorgio Palù; Kazuo Takayama; Ángel Serrano-Aroca; Debmalya Barh; Adam M. Brufsky. Notable sequence homology of the ORF10 protein introspects the architecture of SARS-CoV-2. International Journal of Biological Macromolecules 2021, 181, 801 -809.
AMA StyleSk. Sarif Hassan, Diksha Attrish, Shinjini Ghosh, Pabitra Pal Choudhury, Vladimir N. Uversky, Alaa A.A. Aljabali, Kenneth Lundstrom, Bruce D. Uhal, Nima Rezaei, 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, Amos Lal, Giorgio Palù, Kazuo Takayama, Ángel Serrano-Aroca, Debmalya Barh, Adam M. Brufsky. Notable sequence homology of the ORF10 protein introspects the architecture of SARS-CoV-2. International Journal of Biological Macromolecules. 2021; 181 ():801-809.
Chicago/Turabian StyleSk. Sarif Hassan; Diksha Attrish; Shinjini Ghosh; Pabitra Pal Choudhury; Vladimir N. Uversky; Alaa A.A. Aljabali; Kenneth Lundstrom; Bruce D. Uhal; Nima Rezaei; 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; Amos Lal; Giorgio Palù; Kazuo Takayama; Ángel Serrano-Aroca; Debmalya Barh; Adam M. Brufsky. 2021. "Notable sequence homology of the ORF10 protein introspects the architecture of SARS-CoV-2." International Journal of Biological Macromolecules 181, no. : 801-809.
Immune evasion is one of the unique characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attributed to its ORF8 protein. This protein modulates the adaptive host immunity through down-regulation of MHC-1 (Major Histocompatibility Complex) molecules and innate immune responses by surpassing the host's interferon-mediated antiviral response. To understand the host's immune perspective in reference to the ORF8 protein, a comprehensive study of the ORF8 protein and mutations possessed by it have been performed. Chemical and structural properties of ORF8 proteins from different hosts, such as human, bat, and pangolin, suggest that the ORF8 of SARS-CoV-2 is much closer to ORF8 of Bat RaTG13-CoV than to that of Pangolin-CoV. Eighty-seven mutations across unique variants of ORF8 in SARS-CoV-2 can be grouped into four classes based on their predicted effects (Hussain et al., 2021) [1]. Based on the geo-locations and timescale of sample collection, a possible flow of mutations was built. Furthermore, conclusive flows of amalgamation of mutations were found upon sequence similarity analyses and consideration of the amino acid conservation phylogenies. Therefore, this study seeks to highlight the uniqueness of the rapidly evolving SARS-CoV-2 through the ORF8.
Sk Sarif Hassan; Alaa A. A. Aljabali; Pritam Kumar Panda; Shinjini Ghosh; Diksha Attrish; Pabitra Pal Choudhury; Murat Seyran; Damiano Pizzol; Parise Adadi; Tarek Mohamed Abd El-Aziz; Antonio Soares; Ramesh Kandimalla; Kenneth Lundstrom; Amos Lal; Gajendra Kumar Azad; Vladimir N. Uversky; Samendra P. Sherchan; Wagner Baetas-Da-Cruz; Bruce D. Uhal; Nima Rezaei; Gaurav Chauhan; Debmalya Barh; Elrashdy M. Redwan; Guy W. Dayhoff; Nicolas G. Bazan; Ángel Serrano-Aroca; Amr El-Demerdash; Yogendra K. Mishra; Giorgio Palu; Kazuo Takayama; Adam M. Brufsky; Murtaza M. Tambuwala. A unique view of SARS-CoV-2 through the lens of ORF8 protein. Computers in Biology and Medicine 2021, 133, 104380 -104380.
AMA StyleSk Sarif Hassan, Alaa A. A. Aljabali, Pritam Kumar Panda, Shinjini Ghosh, Diksha Attrish, Pabitra Pal Choudhury, Murat Seyran, Damiano Pizzol, Parise Adadi, Tarek Mohamed Abd El-Aziz, Antonio Soares, Ramesh Kandimalla, Kenneth Lundstrom, Amos Lal, Gajendra Kumar Azad, Vladimir N. Uversky, Samendra P. Sherchan, Wagner Baetas-Da-Cruz, Bruce D. Uhal, Nima Rezaei, Gaurav Chauhan, Debmalya Barh, Elrashdy M. Redwan, Guy W. Dayhoff, Nicolas G. Bazan, Ángel Serrano-Aroca, Amr El-Demerdash, Yogendra K. Mishra, Giorgio Palu, Kazuo Takayama, Adam M. Brufsky, Murtaza M. Tambuwala. A unique view of SARS-CoV-2 through the lens of ORF8 protein. Computers in Biology and Medicine. 2021; 133 ():104380-104380.
Chicago/Turabian StyleSk Sarif Hassan; Alaa A. A. Aljabali; Pritam Kumar Panda; Shinjini Ghosh; Diksha Attrish; Pabitra Pal Choudhury; Murat Seyran; Damiano Pizzol; Parise Adadi; Tarek Mohamed Abd El-Aziz; Antonio Soares; Ramesh Kandimalla; Kenneth Lundstrom; Amos Lal; Gajendra Kumar Azad; Vladimir N. Uversky; Samendra P. Sherchan; Wagner Baetas-Da-Cruz; Bruce D. Uhal; Nima Rezaei; Gaurav Chauhan; Debmalya Barh; Elrashdy M. Redwan; Guy W. Dayhoff; Nicolas G. Bazan; Ángel Serrano-Aroca; Amr El-Demerdash; Yogendra K. Mishra; Giorgio Palu; Kazuo Takayama; Adam M. Brufsky; Murtaza M. Tambuwala. 2021. "A unique view of SARS-CoV-2 through the lens of ORF8 protein." Computers in Biology and Medicine 133, no. : 104380-104380.
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 have shown little or no effect in the clinic so far. 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), 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 13 enveloped positive-sense single-stranded RNA viruses, including SARS-CoV-2. CBNs with low or no toxicity to humans are promising therapeutics against the 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; Tarek Mohamed Abd El-Aziz; Samendra Sherchan; Debmalya Barh; Elrashdy M. Redwan; Nicolas G. Bazan; Yogendra Kumar Mishra; Bruce D. Uhal; Adam Brufsky. Carbon-Based Nanomaterials: Promising Antiviral Agents to Combat COVID-19 in the Microbial-Resistant Era. ACS Nano 2021, 15, 8069 -8086.
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, Tarek Mohamed Abd El-Aziz, Samendra Sherchan, Debmalya Barh, Elrashdy M. Redwan, Nicolas G. Bazan, Yogendra Kumar Mishra, Bruce D. Uhal, Adam Brufsky. Carbon-Based Nanomaterials: Promising Antiviral Agents to Combat COVID-19 in the Microbial-Resistant Era. ACS Nano. 2021; 15 (5):8069-8086.
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; Tarek Mohamed Abd El-Aziz; Samendra Sherchan; Debmalya Barh; Elrashdy M. Redwan; Nicolas G. Bazan; Yogendra Kumar Mishra; Bruce D. Uhal; Adam Brufsky. 2021. "Carbon-Based Nanomaterials: Promising Antiviral Agents to Combat COVID-19 in the Microbial-Resistant Era." ACS Nano 15, no. 5: 8069-8086.
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; Tarek Mohamed Abd El-Aziz; Samendra Sherchan; Debmalya Barh; Elrashdy M Redwan; Nicolas G Bazan; Yogendra Kumar Mishra; Bruce D Uhal; Adam 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, Tarek Mohamed Abd El-Aziz, Samendra Sherchan, Debmalya Barh, Elrashdy M Redwan, Nicolas G Bazan, Yogendra Kumar Mishra, Bruce D Uhal, Adam 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; Tarek Mohamed Abd El-Aziz; Samendra Sherchan; Debmalya Barh; Elrashdy M Redwan; Nicolas G Bazan; Yogendra Kumar Mishra; Bruce D Uhal; Adam Brufsky. 2021. "Carbon-Based Nanomaterials: Promising Antiviral Agents to Combat COVID-19 in the Microbial-Resistant Era." , no. : 1.
Envenomation and death resulting from snakebites represent a significant public health problem worldwide, particularly in tropical and subtropical regions. The WHO has defined snakebite as a neglected tropical health concern. Bites from Macrovipera lebetina obtusa usually cause life-threatening systemic hemodynamic disturbances, reduced functionality of the kidneys, and other serious symptoms, including hypotension shock, edema, and tissue necrosis, at the bite site. Herein, we highlight five cases of M. l. obtusa envenomation that presented with wide-ranging manifestations. Many recovered cases were left with long-term musculoskeletal disabilities. In a particular case, a 15-year-old male patient was envenomed in his palm by an 80-cm M. l. obtusa. Within 12 hours, swelling extended to near the shoulder. Fasciotomy was performed on the forearm and part of the upper arm of this patient. Symptoms of severe localized pain and swelling, dizziness, weakness, low blood pressure, and itching around the bite area were documented. The patient remained in the hospital for 13 days.
Seyed Mahdi Kazemi; Ahmed Al-Sabi; Chengbo Long; Mahmoud I. Shoulkamy; Tarek Mohamed Abd El-Aziz. Case Report: Recent Case Reports of Levant Blunt-Nosed Viper Macrovipera lebetina obtusa Snakebites in Iran. The American Journal of Tropical Medicine and Hygiene 2021, -1, 1 .
AMA StyleSeyed Mahdi Kazemi, Ahmed Al-Sabi, Chengbo Long, Mahmoud I. Shoulkamy, Tarek Mohamed Abd El-Aziz. Case Report: Recent Case Reports of Levant Blunt-Nosed Viper Macrovipera lebetina obtusa Snakebites in Iran. The American Journal of Tropical Medicine and Hygiene. 2021; -1 (aop):1.
Chicago/Turabian StyleSeyed Mahdi Kazemi; Ahmed Al-Sabi; Chengbo Long; Mahmoud I. Shoulkamy; Tarek Mohamed Abd El-Aziz. 2021. "Case Report: Recent Case Reports of Levant Blunt-Nosed Viper Macrovipera lebetina obtusa Snakebites in Iran." The American Journal of Tropical Medicine and Hygiene -1, no. aop: 1.
The huge global expansion of the COVID-19 pandemic caused by the novel SARS-corona virus-2 is an extraordinary public health emergency. The unavailability of specific treatment against SARS-CoV-2 infection necessitates the focus of all scientists in this direction. The reported antiviral activities of guanidine alkaloids encouraged us to run a comprehensive in silico binding affinity of fifteen guanidine alkaloids against five different proteins of SARS-CoV-2, which we investigated. The investigated proteins are COVID-19 main protease (Mpro) (PDB ID: 6lu7), spike glycoprotein (PDB ID: 6VYB), nucleocapsid phosphoprotein (PDB ID: 6VYO), membrane glycoprotein (PDB ID: 6M17), and a non-structural protein (nsp10) (PDB ID: 6W4H). The binding energies for all tested compounds indicated promising binding affinities. A noticeable superiority for the pentacyclic alkaloids particularly, crambescidin 786 (5) and crambescidin 826 (13) has been observed. Compound 5 exhibited very good binding affinities against Mpro (ΔG = −8.05 kcal/mol), nucleocapsid phosphoprotein (ΔG = −6.49 kcal/mol), and nsp10 (ΔG = −9.06 kcal/mol). Compound 13 showed promising binding affinities against Mpro (ΔG = −7.99 kcal/mol), spike glycoproteins (ΔG = −6.95 kcal/mol), and nucleocapsid phosphoprotein (ΔG = −8.01 kcal/mol). Such promising activities might be attributed to the long ω-fatty acid chain, which may play a vital role in binding within the active sites. The correlation of c Log P with free binding energies has been calculated. Furthermore, the SAR of the active compounds has been clarified. The Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) studies were carried out in silico for the 15 compounds; most examined compounds showed optimal to good range levels of ADMET aqueous solubility, intestinal absorption and being unable to pass blood brain barrier (BBB), non-inhibitors of CYP2D6, non-hepatotoxic, and bind plasma protein with a percentage less than 90%. The toxicity of the tested compounds was screened in silico against five models (FDA rodent carcinogenicity, carcinogenic potency TD50, rat maximum tolerated dose, rat oral LD50, and rat chronic lowest observed adverse effect level (LOAEL)). All compounds showed expected low toxicity against the tested models. Molecular dynamic (MD) simulations were also carried out to confirm the stable binding interactions of the most promising compounds, 5 and 13, with their targets. In conclusion, the examined 15 alkaloids specially 5 and 13 showed promising docking, ADMET, toxicity and MD results which open the door for further investigations for them against SARS-CoV-2.
Amr El-Demerdash; Ahmed Metwaly; Afnan Hassan; Tarek Abd El-Aziz; Eslam Elkaeed; Ibrahim Eissa; Reem Arafa; James Stockand. Comprehensive Virtual Screening of the Antiviral Potentialities of Marine Polycyclic Guanidine Alkaloids against SARS-CoV-2 (COVID-19). Biomolecules 2021, 11, 460 .
AMA StyleAmr El-Demerdash, Ahmed Metwaly, Afnan Hassan, Tarek Abd El-Aziz, Eslam Elkaeed, Ibrahim Eissa, Reem Arafa, James Stockand. Comprehensive Virtual Screening of the Antiviral Potentialities of Marine Polycyclic Guanidine Alkaloids against SARS-CoV-2 (COVID-19). Biomolecules. 2021; 11 (3):460.
Chicago/Turabian StyleAmr El-Demerdash; Ahmed Metwaly; Afnan Hassan; Tarek Abd El-Aziz; Eslam Elkaeed; Ibrahim Eissa; Reem Arafa; James Stockand. 2021. "Comprehensive Virtual Screening of the Antiviral Potentialities of Marine Polycyclic Guanidine Alkaloids against SARS-CoV-2 (COVID-19)." Biomolecules 11, no. 3: 460.
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.
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.
Envenomation by viperid snakes may lead to severe bleeding, consumption coagulopathy, and thrombotic microangiopathy symptoms. The exact etiology or toxins responsible for thrombotic microangiopathy symptoms after snake envenomation remain obscure. Snake C-type lectin-like proteins (snaclecs) are one of the main non-enzymatic protein constituents in viper venoms, of which a majority are considered as modulators of thrombosis and hemostasis. In this study, we demonstrated that two snaclecs (mucetin and stejnulxin), isolated and identified from Protobothrops mucrosquamatus and Trimeresurus stejnegeri venoms, directly induced platelet degranulation and clot-retraction in vitro, and microvascular thrombosis has been confirmed in various organs in vivo. These snaclecs reduced cerebral blood flow and impaired motor balance and spatial memories in mice, which partially represent the thrombotic microangiopathy symptoms in some snakebite patients. The functional blocking of these snaclecs with antibodies alleviated the viper venom induced platelet activation and thrombotic microangiopathy-like symptoms. Understanding the pathophysiology of thrombotic microangiopathy associated with snake envenoming may lead to emerging therapeutic strategies.
Chengbo Long; Ming Liu; Huiwen Tian; Ya Li; Feilong Wu; James Mwangi; Qiumin Lu; Tarek Mohamed Abd El-Aziz; Ren Lai; Chuanbin Shen. Potential Role of Platelet-Activating C-Type Lectin-Like Proteins in Viper Envenomation Induced Thrombotic Microangiopathy Symptom. Toxins 2020, 12, 749 .
AMA StyleChengbo Long, Ming Liu, Huiwen Tian, Ya Li, Feilong Wu, James Mwangi, Qiumin Lu, Tarek Mohamed Abd El-Aziz, Ren Lai, Chuanbin Shen. Potential Role of Platelet-Activating C-Type Lectin-Like Proteins in Viper Envenomation Induced Thrombotic Microangiopathy Symptom. Toxins. 2020; 12 (12):749.
Chicago/Turabian StyleChengbo Long; Ming Liu; Huiwen Tian; Ya Li; Feilong Wu; James Mwangi; Qiumin Lu; Tarek Mohamed Abd El-Aziz; Ren Lai; Chuanbin Shen. 2020. "Potential Role of Platelet-Activating C-Type Lectin-Like Proteins in Viper Envenomation Induced Thrombotic Microangiopathy Symptom." Toxins 12, no. 12: 749.
Zoufaly, A. et al. Human recombinant soluble ACE2 in severe COVID-19. Lancet Respiratory Med. https://doi.org/10.1016/S2213-2600(20)30418-5 (2020). Walls, A. C. et al. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 181, 281–292.e286 (2020). CAS Article Google Scholar Kuba, K. et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat. Med. 11, 875–879 (2005). CAS Article Google Scholar Monteil, V. et al. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell 181, 905–913.e907 (2020). CAS Article Google Scholar Haschke, M. et al. Pharmacokinetics and pharmacodynamics of recombinant human angiotensin-converting enzyme 2 in healthy human subjects. Clin. Pharmacokinetics 52, 783–792 (2013). CAS Article Google Scholar Download references Department of Cellular and Integrative Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229-3900, USA Tarek Mohamed Abd El-Aziz & James D. Stockand Zoology Department, Faculty of Science, Minia University, El-Minia, 61519, Egypt Tarek Mohamed Abd El-Aziz College of Engineering and Technology, American University of the Middle East, Kuwait, Kuwait Ahmed Al-Sabi You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar Correspondence to Tarek Mohamed Abd El-Aziz. The authors declare no competing interests. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Reprints and Permissions Abd El-Aziz, T.M., Al-Sabi, A. & Stockand, J.D. Human recombinant soluble ACE2 (hrsACE2) shows promise for treating severe COVID19. Sig Transduct Target Ther 5, 258 (2020). https://doi.org/10.1038/s41392-020-00374-6 Download citation Received: 10 October 2020 Revised: 15 October 2020 Accepted: 16 October 2020 Published: 03 November 2020 DOI: https://doi.org/10.1038/s41392-020-00374-6
Tarek Mohamed Abd El-Aziz; Ahmed Al-Sabi; James D. Stockand. Human recombinant soluble ACE2 (hrsACE2) shows promise for treating severe COVID19. Signal Transduction and Targeted Therapy 2020, 5, 1 -2.
AMA StyleTarek Mohamed Abd El-Aziz, Ahmed Al-Sabi, James D. Stockand. Human recombinant soluble ACE2 (hrsACE2) shows promise for treating severe COVID19. Signal Transduction and Targeted Therapy. 2020; 5 (1):1-2.
Chicago/Turabian StyleTarek Mohamed Abd El-Aziz; Ahmed Al-Sabi; James D. Stockand. 2020. "Human recombinant soluble ACE2 (hrsACE2) shows promise for treating severe COVID19." Signal Transduction and Targeted Therapy 5, no. 1: 1-2.
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.