 Welcome again, Abdul. Yeah. Thank you very much. Abdul, you have 20 minutes for the presentation and five minutes for interaction for the floor. OK. OK, thank you very much for letting me do this presentation. Thank you, Ali Hassan, for your invitation. Today, I will talk about coronavirus, fighting against coronavirus, a competition by physics approach. Actually, all of us have some, I mean, encountered this pandemic. And all of us know a lot of information about COVID-19. So today, I will start my talk first. I am Abdul Fiki from my physics department at Cairo University. I'm an associate professor since last year. And I am a junior associate at the ICTP. Today, I will talk about the pandemic, how it affects us, and how can physics help in fighting against COVID-19. So all of us know that more than 1 million people are gone due to the pandemic. And more than 50 million are infected with this virus. For us to know that this is the seventh defined human coronavirus rate. So we have six different strains of human coronavirus during the last 20 years. And we will see how physics can help fighting against COVID-19. These are the immersive human coronavirus strains that have some symptoms like flu or cold. And the most affecting three types, three strains, are the SARS-CoV, which started in 2002. And MERS, or Middle Isis Baratulis Syndrome coronavirus, started 2012. And the current COVID-19, or SARS-CoV-2, there is an intermediate host, which are CVT-CAT in the case of SARS, Dromedary Camel in the case of MERS. And it is unknown today which is the intermediate host that transfers this coronavirus to human. But Bangolin is a snake, maybe the host, the intermediate host. So today we talk about the coronavirus disease. So sorry. So Africa is less affected with the human coronavirus with about 4% of the total infection and total deaths in Africa. And the research conducted in Africa is about 2.8% of the total research on COVID-19. This is less than the total population of Africa, which is 17% of the world population. But still we have some, I mean, we can help people around the world to get the ride of this infectious, high infectious disease. So today I will focus on the targeting of COVID-19. Targeting meaning that we can select some proteins of this virus by vaccine, by antivirals, by immune modulators. All of these are targeting strategies that we can work in. Today I will focus on the antivirus and vaccine developments. These are the proteins of the SARS-CoV-2 that we can target, the structural protein and non-structural proteins. For structural proteins, the most important is the spike protein. We have envelope protein, membrane protein, naprocapsid protein. And for the non-structural proteins are the proteins that it's inside the host cell, like the papine-like proteins, and the main proteins, and the RNA-dependent RNA polymerase, which are the most important non-structural protein of the SARS-CoV-2. The red-colored proteins are that I used to target in my research during this year. But today I will talk about the spike protein only. So spike protein is a surface oxo-bose protein for the virus, and it is a hetero-trimeric. We can see here three copies of the protein that work together in a homotrimeric. Sorry, homotrimeric. And we have two populations, a post-fusion, which is minority, and the brief fusion, isoforms, which is a majority of the surface spike proteins. This perfusion are some are closed. Here we can see this region is called the receptor binding domain, this domain. So we can see all of the domain are closed, or one is open, or two are open. OK, this is over the virus particle. After infection, the brief fusion isoform transfer to the post-fusion in order for the virus to enter the cell. So the main function of the spike protein is host recognition. This is recognized some host cell receptor, like ACE2. Entry through the post-fusion isoform, the virus can fuse with the membrane of the host cell. And last is escaping the virus, the virus from the host immune system. Due to the glycosylation that present here, we can see a lot of glycosylation sites over the spike protein that help the virus escape the immune system. So now I'm talking about a host cell protein called H2 protein A5, HSB A5, or glycosylated protein GRB78, which is a host receptor that have a function inside the cell in the normal condition. This is a master of the unfolded protein response. Here we are. As we can see from this figure, we have two domains. There's a nucleotide binding domain and substrate binding domain. This protein has a main function inside the endoblasmic reticulum of the cell as it captures unfolded proteins and mediates through the degradation or refolding mechanism. So it's function inside the ER as endoblasmic reticulum associated degradation mechanism, captures unfolded proteins. And GRB has a function over the cell surface, which is called cell surface GRB78, which act as a receptor. Also, GRB is executed to the bloodstream, so it have some immune response. And some work was done for how to shake the concentration of GRB in the blood and detect if the patient is COVID-19 infected or not. So the complementary test with the PCR and other tests that used to check the infectivity of SARS-CoV-2. Here, we can see the nucleotide binding domain, how the ATB, ATB-ADB binding affects the structural flexibility and the structural arrangement of the substrate binding domain. And here, we have two conditions, normal conditions where there is no stress on the cell. So the GRB78 is bound to three important enzymes, which are ATF6 and BERK and the IR1. These three enzymes are important in some physical function inside the cell, like the enhanced folding. So under stress condition, GRB is released these enzymes, make it available for its function. So the IR1 enhanced folding, ATF6, move to the apparatus where it is believed and go to the nucleus to act as a nuclear activator for the GRB over-expression. While the BERK is working as inhibits the translation and protein synthesis. So all over this cycle, we have a lot of GRB that over-expressed in the cell and transfigured from the ER to cytoplasm, then to the membrane of the cell to be available for viral or fungal basogen recognition. There is a lot of work that's done on viral or fungal infection that assisted with the presence of the CS GRB78 over the host cell. So in this study, I worked with some of my students on how GRB-expression can affect COVID-19 infectivity. We used computational methods like sequence alignment, like protein docking, and then the mercadimic simulation to check how is the binding can occur between GRB78 and COVID-19 spike protein. So here is a sequence alignment we used to check the different spike protein from the different human coronavirus strains. We have here the seven strains of the human coronavirus, along with the new coronavirus SARS-CoV-2. And we define here four regions that are able to attach to the spike protein. This selection is based on sequence identity and the presence of the disulfide bond in the first and last amino acid, GSS team. We check the sequence identity for each region, and we check the hydrophobicity index for each region. And we detect that region four or region five may be the best region for a spike recognition. After validation of the structural binding or the docking between the different regions, we define this region four, which is this eight amino acid as the best region that can recognize SARS-CoV-2 spike protein. So this is a viron. This is a spike protein. This is a trimeric spike. And this is the region four that can detect the ERB-78. OK. Now, this is the model that we built for the binding between GRB-78 and SARS-CoV monomer. So here is the binding site. We can see this is the region four, the red one. And this is the amino acid in the substrate binding domain beta of the GRB-78. So now, this is the model we built under a stress condition based on the infectivity of the virus or any stress response to the cell. GRB is overexpressed in the ER, released to the membrane, and becomes a cell surface exposed and can detect the spike protein of the coronavirus. So this work has been published in Journal Confection and followed by this letter to the same journal. We have changed the model a little bit by using this sort of structure of the channel protein. And this is ACE2, the receptor of the SARS-CoV-2 and part of the spike RBD or receptor binding domain. Here we make protein-brutin docking between GRB surface, GRB-78 and the spike RB-RB. And here is the binding site of this GRB to the complex. As we can see here, GRB can be surface exposed, but some protein have to carry this GRB-78 in order for it to be able to interact with this complex. So now we can come across the different coronaviruses strains. Can we see if the other coronaviruses can be used as a vaccine or maybe held in vaccine development? Here is part of the sequence alignment, multiple sequence alignment of the different human coronaviruses. As we can see here, there is three finger brains for the maybe the vaccination or cross-vaccination. We can see here this amino acid, cysteine, and this amino acid, which is proline or glycine. And here is the other cysteine amino acid, maybe a finger brain for recognition of the GRB. And this work is based on sequence alignment and also molecular dynamics simulation of the GRB. And we predict in this that we... Immersed coronaviruses, which are the coronaviruses that has low infectivity, like NL63, 229E and OC43 and HKU1, maybe cross-vaccinated with SARS-CoV-2. So we have here all the conditions for this, for Immersed Human Coronaviruses. And this work was published in Frontier in Pharmacology as a perspective. Now, we came to another point which is important, other viruses. Can other viruses be detected by this protein? Yes. We predicted the Ebola virus, Glockovidin-Gb1 to the GRB-78, a human babyloma virus, E6 to the GRB-78 and Zika virus to GRB. But we don't have time to talk about these viruses. So we focus on the coronaviruses now. Now, GRB-78 can be used to targeting strategy against coronaviruses. We can target the GRB surface GRB-78 with peptides or monoclonal antibodies or phytochemicals. There is a lot of work that used these three types of targeting mechanism against different types of cancers because the surface GRB is overexaggerated in any type of cell stress, like different types of cancer. So in this study, I focus on some natural compounds that can interact with surface GRB and so can inhibit the recognition between spike protein and GRB-78. Sorry, up to five minutes, please. OK, no problem. So now this is some natural compounds that based on natural product, we can see here all of these phytochemicals. This is four phytochemicals. Sorry, these are four phytoestrogens. And this is some oils, like from alive oil and the chlorogenic acid. Here we can see the cinnamon and cymoquinone from the lexid and other ingredients that we can find in our food. OK, so I tested these products or these natural products with GRB, how it can bind to the substrate, bind to the mean beta of the GRB. After making the molecular simulation for the GRB as a whole protein and see how is the dynamics of the different regions of the protein, this is the most dynamical part, which is the substrate binding alpha, which is important in some motion of this domain over the substrate binding beta. Because as a normal function, substrate binding alpha move to cover the substrate binding beta, domain beta. OK, so these are the docking we have done using autodocvina after clustering of the molecular simulation data or trajectories of GRB. And we can find these phytoestrogens are the best compounds in binding GRB78 substrate binding mean beta. We have here also some compounds that have best results. So these are selected three compounds that have high binding energy minus 8.3 minus 10 minus 8.6 and minus 6.9. So as a conclusion, we can say that we built a model for the cell surface GRB binding to the spike protein. And we try to inhibit the recognition side of the cell surface GRB with some phytochemicals. And we are working in this region to include peptides and maybe the monoclonal antibody in inhibiting the cell surface GRB78. OK, so thanks to my supervisor, to Dr. Wailishimi and my supervisor, and as a voice doctor, Dr. Khaled Barakar, Dr. Professor Salam Tardawi and Professor Ali Hassan Ali for his assistance and for helping me to do this work to my 5th department at Karen University. Thank you very much. I finish now the presentation. So if someone has questions, I'm happy to ask to her. Yeah, thank you very much. Thank you, Abdul. So you can unmute yourself and ask questions, please. Can I talk, yes? Yes, please, yes, yes. I am Abdul. Shilvia, did you open your video? Am I OK? Can you see me? Yeah, your video is there. Thanks. OK, I am a bit puzzled by your lack of specificity. You said that you can predict, at least you predict an interaction also with the E6 papillomavirus protein, with proteins from Ebola, which are very different. How do you explain that? First, we have different papers that say that different viruses can be recognized with H2O protein A5. But there is no prediction of how the binding occur. So I predict the binding site between the GRB78 and these different viral proteins. So we can see here in the Ebola virus, the glycoprotein GB1 is mentioned in papers that it is maybe recognized by GRB. So I make protein-protein docking and see which is the best regions that can bind. So I predict the binding site. And for the human papillomavirus E6, this is a protein that, I mean, since size inside the host cell. So it is mentioned in the review and other papers that E6 is stabilized by H2O proteins. But how this interaction occur is not mentioned. So I use a prediction to check the binding site between the E6 and the GRB78. And this also for the gyrovirus and the papillomavirus E2. So I just make prediction of the binding site. Based on experimental data that is public. Because no, I was just surprised by the large number of very different proteins that were involved. But OK. Thank you very much. May I ask a question? Hi, Abdo. This is Loredana. Nice to see you. So I have just one question. Do you relate to your calculations to correlate to any experimental platform, model experimental platform? Do you have any kind of data available on, I don't know, this GRB embedded in the membrane and recognizing the RBD of the spike? And which are the types of the experiment you confront to? Yeah, for my study, it is totally computational. I don't have any experimental data. I'm trying to make some collaboration with other people. But until now, I don't have any established collaboration with the experimental validation of the recognition of the spike with GRB78. But a lot of research have some correlation between the GRB level in the cell and SARS-CoV-2 infectivity. So people with COVID-19 are expressed GRB more than people don't have the COVID-19 infection. So yes, I am happy to make any collaboration with experimental people. But until now, I don't have established a platform. OK, thank you. Thank you very much. Yeah, Ali, you can ask. Yeah, so thank you very much, Abdo. I have two questions for you. One is you didn't say anything about numbers with respect to the energetics. So you computed, I guess, you got some estimates of binding free energies between these two sites that you were studying. Yeah, just order of magnitude. What are the numbers? Number for what? So in the GRP, so go back. So for example, the binding free energy between the RBD domain and the GRP, what is the binding free energy? Yeah, I used for this model. Yeah, yeah, exactly. I used here the Hadox software to predict binding mode and binding energy between the two proteins. So the binding energy was like this, 100 minus 100, 143. With the Hadox, I mean, this is the Hadox score. This is in kilojoules per mole or KKLs per mole or what? Yeah, yeah, and this is the Hadox score, not KKL. Ah, it's normalized somehow, OK. Yeah, yeah, yeah. So this is not the actual binding energy. And this number is a large number, is what you're telling me. Yeah, yeah, yeah, but this one is not actual binding energy. It is just a score for the binding. OK, I understand. My second question is related to the talk from yesterday by Daniel, who also was alluding to the role of natural products. Yeah. Can you comment a bit on a class of natural products that he was talking about versus you, and yeah. Yeah, I see it's the last lecture of Daniel, and he have working with some different group of natural product. So for me, I was working with this natural product because, I mean, before coronavirus, I was working on GRB 78. So this is some combination of that natural product that I used before. And I tried to use GRB and found this is found in our food. So I mean, it is easy to find and not expensive. We can see some items here from the honeybee, from the cinnamon, from the black seed. So I mean, these items we can find in our food, in our vegetable and fruits. So it is, I mean, we can eat these vegetable fruits and honeybee and like natural product, and we prevent not only the SARS-CoV-2, but also any stress to the cell. So the message is we should move to an African diet. Yeah. This is the message. OK, thanks. Thank you. Thank you.