SARS-CoV-2, which causes severe pneumonia epidemics, probably originated from Chinese horseshoe bats, but the intermediate and host range is still unknown. ACE2 is the entry receptor for SARS-CoV-2. The binding capacity of SARS-CoV-2 spike protein to ACE2 is the critical determinant of viral host range and cross-species infection. Here, we used an in silico approach to predict the potential animals range with high susceptibility to SARS-CoV-2 by modelling and studying the Spike–ACE2 interaction of 22 domestic and wild animals. Our results showed that all studied animals are potentially susceptible to SARS-CoV-2 infection with a slight difference in the binding affinity and stability of their ACE2–RBD complexes. Furthermore, we identified a specific substitution of tyrosine to histidine at position 41 in ACE2 that likely reduces the affinity to SARS-CoV-2 in horses and greater horseshoe bats. These results may help to provide important insights into SARS-CoV-2 host range which will make it possible to control the spread of the virus and identify animal models that could be used for screening antiviral drugs or vaccine candidates against SARS-CoV-2.

The novel coronavirus, SARS-CoV-2, has infected more than 10 million people and caused more than 502,539 deaths worldwide as of June 2020. The explosive spread of the virus and the rapid increase in the number of cases require the immediate development of effective therapies and vaccines as well as accurate diagnosis tools. The pathogenesis of the disease is triggered by the entry of SARS-CoV-2 via its spike protein into ACE2-bearing host cells, particularly pneumocytes, resulting in overactivation of the immune system, which attacks the infected cells and damages the lung tissue. The interaction of the SARS-CoV-2 receptor binding domain (RBD) with host cells is primarily mediated by the N-terminal helix of the ACE2; thus, inhibition of the spike-ACE2 interaction may be a promising therapeutic strategy for blocking the entry of the virus into host cells. In this paper, we used an in-silico approach to explore small-molecule α-helix mimetics as inhibitors that may disrupt the attachment of SARS-CoV-2 to ACE2. First, the RBD-ACE2 interface in the 6M0J structure was studied by the MM-GBSA decomposition module of the HawkDock server, which led to the identification of two critical target regions in the RBD. Next, two virtual screening experiments of 7236 α-helix mimetics from ASINEX were conducted on the above regions using the iDock tool, which resulted in 10 candidates with favorable binding affinities. Finally, the stability of RBD complexes with the top-two ranked compounds was further validated by 40 ns MD simulations using Desmond package of Schrodinger.

The coronavirus disease 19 (COVID-19) is a highly contagious and rapidly spreading infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In some cases, the disease can be fatal which resulted in more than one million deaths worldwide according the WHO. Currently, there is no effective vaccine or treatment for COVID-19, however many small-molecule inhibitors have shown potent antiviral activity against SARS-CoV-2 and some of them are now under clinical trials. Despite their promising activities, the development of these small molecules for the clinical use can be limited by many factors like the off-target effect, the poor stability, and the low bioavailability. The clusters of differentiation CD147, CD209, CD299 have been identified as essential entry co-receptors for SARS-CoV-2 species specificity to humans, although the underlying mechanisms are yet to be fully elucidated. In this paper, protein-protein docking was utilized for identifying the critical epitopes in CD147, CD209 and CD299 which are involved in the binding with SARS-CoV-2 Spike receptor binding domain (RBD). The results of binding free energies showed a high affinity of SARS-CoV-2 RBD to CD299 receptor which was used as a reference to derive hypothetical peptide sequences with specific binding activities to SARS-CoV-2 RBD. Molecular docking and molecular dynamics simulations of the newly designed peptides showed favorable binding features and stability with SARS-CoV-2 RBD and therefore can be further considered as potential candidates in future anti-SARS CoV-2 drug discovery studies.

The transmembrane glycoprotein CD36, which is responsible of the metabolic disorders, and the elevated intake of fat induces lipid buildup, is a multifunctional scavenger receptor signaling those functions in high-affinity tissue uptake of long-chain fatty acids. In this study, we used series of molecular dynamics simulations of the wild type and mutants types K164A CD36 protein interacting with one palmitic acid (PLM) besides simulations of the wild type interacting with the three PLM to find out the mechanism of the functioning of the complex CD36/Fatty acids and the unraveling of the role of the mutation. Additionally we determined whether Lys164, mostly exposed to protein surface, played important roles in fatty acid uptake. These simulations revealed, the conformational changes induced by Lys164 residue and the altered interactions induced by the mutagenesis of surface lysine that was badly influencing the folding, utility, solubility, and stability form of the variant. Furthermore, Lys164 residue provided the structural basis of forming an opening at the region of principal portal for the dissociation of palmitic acid. The results of our simulations revealed hole two fatty acids found in CD36 cavity structure and it was the most preferred to CD36 structure stabilization.

The novel coronavirus, SARS-CoV-2, has infected more than 10 million people and caused more than 502,539 deaths worldwide as of June 2020. The explosive spread of the virus and the rapid increase in the number of cases require the immediate development of effective therapies and vaccines as well as accurate diagnosis tools. The pathogenesis of the disease is triggered by the entry of SARS-CoV-2 via its spike protein into ACE2-bearing host cells, particularly pneumocytes, resulting in overactivation of the immune system, which attacks the infected cells and damages the lung tissue. The interaction of the SARS-CoV-2 receptor binding domain (RBD) with host cells is primarily mediated by the N-terminal helix of the ACE2; thus, inhibition of the spike-ACE2 interaction may be a promising therapeutic strategy for blocking the entry of the virus into host cells. In this paper, we used an in-silico approach to explore small-molecule α-helix mimetics as inhibitors that may disrupt the attachment of SARS-CoV-2 to ACE2. First, the RBD-ACE2 interface in the 6M0J structure was studied by the MM-GBSA decomposition module of the HawkDock server, which led to the identification of two critical target regions in the RBD. Next, two virtual screening experiments of 7236 α-helix mimetics from ASINEX were conducted on the above regions using the iDock tool, which resulted in 10 candidates with favorable binding affinities. Finally, the stability of RBD complexes with the top-two ranked compounds was further validated by 40 ns MD simulations using Desmond package of Schrodinger.<br>

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