In Silico Exploration of CD200 as a Therapeutic Target for COVID-19

SARS-CoV-2, the pathogen causing COVID-19, continues to pose a significant threat to public health and has had major economic implications. Developing safe and effective vaccines and therapies offers a path forward for overcoming the COVID-19 pandemic. The presented study, performed by using the informational spectrum method (ISM), representing an electronic biology-based tool for analysis of protein–protein interactions, identified the highly conserved region of spike protein (SP) from SARS-CoV-2 virus, which is essential for recognition and targeting between the virus and its protein interactors on the target cells. This domain is suggested as a promising target for the drug therapy and vaccines, which could be effective against all currently circulating variants of SARS-CoV-2 viruses. The analysis of the virus/host interaction, performed by the ISM, also revealed OX-2 membrane glycoprotein (CD200) as a possible interactor of SP, which could serve as a novel therapeutic target for COVID-19 disease. © 2024 by the authors

Simple Theoretical Criterion for Selection of Natural Compounds with Anti-COVID-19 Activity

A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the leading threat to global health. An effective antiviral could not only help those still vulnerable to the virus but could be a critical treatment if a virus emerges toward evading coronavirus disease 2019 (COVID-19) vaccines. Despite the significant efforts to test already-approved drugs for their potential to kill the virus, researchers found very few actually worked. Methods: The present report uses the electronic molecular descriptors, the quasi-valence number (AQVN), and the electron-ion interaction potential (EIIP), for the analysis of natural compounds with proven therapeutic activity against the COVID-19. Results: Based on the analysis of the electronic properties of natural compounds which are effective against SARS-CoV-2 virus the simple theoretical criterion for the selection of candidate compounds for the treatment of COVID-19 is proposed. Conclusions: The proposed theoretical criterion can be used for the identification and optimization of new lead compounds for the treatment of the COVID-19 disease and for the selection of the food and food supplements which could have a beneficial effect on COVID-19 patients

Apolipoprotein B gene polymorphisms in patients from Serbia with ischemic cerebrovascular disease

The plasma concentration of apoB has recently been reported to be the best lipid predictor of coronary heart disease. The possible associations of genetic markers in the apolipoprotein B gene (XbaI, EcoRI, MspI, Ins/Del, and 4311 A/G polymorphisms) were evaluated in patients with ischemic cerebrovascular disease (ICVD) and controls of equivalent BMI. The odds ratio for ICVD in the X+X+ genotype was 2.22, 95% CI 1.24-3.96 (P<0.05), while that for ICVD in the Ins/Ins genotype was 2.82, 95% CI 1.57-5.06 (P<0.05). The patients had significantly higher frequency of the 4311A allele compared to the controls (P<0.01). Our results support the assumption that apoB gene polymorphisms may contribute to the extent of cerebrovascular disease risk

In silico Therapeutics for Neurogenic Hypertension and Vasovagal Syncope

Neurocardiovascular diseases (NCVD) are the leading cause of death in the developed world and will remain so till 2020. In these diseases the pathologically changed nervous control of cardiovascular system has the central role. The actual NCV syndromes are neurogenic hypertension, representing the sympathetically mediated disorder, and vasovagal syncope, which is the vagally mediated disorders. Vasovagal syncope, the disease far from its etiological treatment, could benefit from recruiting and application of antimuscarinic drugs used in other parasympathetic disorders. The informational spectrum method (ISM), a method widely applied for the characterization of protein-protein interactions in the field of immunology, endocrinology and anti HIV drug discovery, was applied for the first time in the analysis of neurogenic hypertension and vasovagal syncope therapeutic targets. In silico analysis revealed the potential involvement of apelin in neurogenic hypertension. Applying the EIIP/ISM bioinformatics concept in investigation of drugs for treatment of vasovagal syncope suggests that 78% of tested antimuscarinic drugs could have anti vasovagal syncope effect. The presented results confirm that ISM is a promissing method for investigation of molecular mechanisms underlying pathophysiological proceses of NCV syndromes and discovery of therapeutics targets for their treatment

An Overview of S-Genotype Diversity in Sweet Cherry Landraces Grown in the Central Region of the Republic of Serbia

Identification of the S-genotypes in landraces is a crucial step in the molecular characteri- zation of Serbian autochthonous sweet cherry germplasm. It is also of enormous significance for bre- eders and growers, as this fruit species exhibits a gametophytic self-incompatibility, controlled by the multi-allelic two genes of the S-locus. The aim of this study was to summarize known information and reveal new data on the S-alleles in 23 sweet cherry landraces originating in the Republic of Ser- bia. The use of polymerase chain reaction (PCR) with consensus primers for the second intron of S- RNase, primers specific for S-RNase and certain SFB alleles, along with DNA fragment analysis using fluorescently labelled forward primers to amplify both the S-RNase first intron and the SFB in- tron, revealed 10 alleles (S1 to S6, S9, S12, S13 and S22) that generated the following 13 S-genotypes: S1S2 (one landrace), S1S4 (one landrace), S1S5 (one landrace), S2S3 (four landraces), S3S4 (two lan- draces), S3S5 (two landraces), S3S6 (three landraces), S3S9 (two landraces), S3S12 (two landraces), S4S5 (one landrace), S4S13 (one landrace), S5S22 (one landrace) and S6S9 (two landraces). The most frequent S-allele and S-genotype in this sweet cherry material were S3 and S2S3, with occurrence fre- quencies of 32.6% and 17.4%, respectively. Based on the obtained results, the sweet cherry landraces were assigned to 12 incompatibility groups and one group of universal donors (‘0’). These results pro- vide important information about their cross-compatibility and the diversity of the S-locus in Serbian sweet cherry germplasm

Identification of the new candidate NLRP3 inhibitor using combined computational approach

The NOD-like receptor pyrin domain-containing protein 3 (NLRP3), an important intracellular sensor in the innate immune system, detects a plethora of exogenous and endogenous stimuli, leading to inflammasome formation and caspase-1 activation. More recently, it emerged as an attractive drug target due to abnormal NLRP3 inflammasome activation implicated in many acute and chronic diseases (including diabetes, atherosclerosis, metabolic syndrome, cardiovascular, and neurodegenerative diseases) [1]. Several direct NLRP3 inhibitors that block its ATPase activity by keeping it in closed conformation have been reported [1,2]. Some of them have entered clinical trials, but still, none of them is FDA approved. A powerful strategy in identifying potential NLRP3 inhibitors can be in silico drug repurposing of compounds with already known safety profiles. In this study, we performed a virtual screening protocol that considers both long- and short-range interactions between molecules. First, the Informational spectrum method developed for small molecules was applied for searching the Drugbank database. Selected candidates were filtered by successive cross-correlation spectra analysis. Finally, after molecular docking, we identified the most promising candidate and proposed it for further experimental testing.Book of Abstracts: 9th Conference of Young Chemists of Serbia Novi Sad, 4th November 202

Drug Repurposing for Candidate SARS-CoV-2 Main Protease Inhibitors by a Novel in Silico Method

The SARS-CoV-2 outbreak caused an unprecedented global public health threat, having a high transmission rate with currently no drugs or vaccines approved. An alternative powerful additional approach to counteract COVID-19 is in silico drug repurposing. The SARS-CoV-2 main protease is essential for viral replication and an attractive drug target. In this study, we used the virtual screening protocol with both long-range and short-range interactions to select candidate SARS-CoV-2 main protease inhibitors. First, the Informational spectrum method applied for small molecules was used for searching the Drugbank database and further followed by molecular docking. After in silico screening of drug space, we identified 57 drugs as potential SARS-CoV-2 main protease inhibitors that we propose for further experimental testing. © 2020 by the authors

Combined in silico and experimental approach to identify the peptide mimetic of the nanobody that stabilize functional conformational state of the beta2 adrenergic receptor (β2AR)

Stabilization of specific G-protein coupled receptor (GPCR) conformation is achieved by ligand binding to orthosteric or allosteric sites on a GPCRs. A crucial unresolved issue in GPCRs activation/signaling is the role of receptor structural conformations in G protein/effector protein selection. One of the possible approaches to get comprehensive depiction of GPCRs activation dynamics are molecular simulations and recently described nanobody-derived intrabodies. Monomeric single-domain antibody (nanobody) from the Camelid family was found to allosterically bind to and stabilizes distinct conformational states of the β2AR. By applying informational spectrum method (ISM), a virtual spectroscopy method for investigation of the protein-protein interactions, we have designed peptide mimetic of the nanobody related to the β2AR (nanobody derived peptide, NDP). Further, interaction between NDP and the ligand-bound β2AR active conformation have been studied by protein-peptide docking, molecular dynamics simulations and metadynamics calculations of free energy binding. Finally, the affinity of selected NDPs towards agonist-activated β2AR was also studied by microscale thermophoresis (MST) and by bioluminescence resonance energy transfer (BRET) based β-arrestin 2 recruitment assay. MST data predicted micromolar range interaction of selected NDPs with the β2AR, while the preliminary β-arrestin 2 recruitment results suggest prospective further modification and optimization of NDPs toward effective modulators of the β2AR.Special Edition of Book of Abstract

Patterns of human and porcine gammaherpesvirus-encoded BILF1 receptor endocytosis

The viral G-protein-coupled receptor (vGPCR) BILF1 encoded by the Epstein–Barr virus (EBV) is an oncogene and immunoevasin and can downregulate MHC-I molecules at the surface of infected cells. MHC-I downregulation, which presumably occurs through co-internalization with EBV-BILF1, is preserved among BILF1 receptors, including the three BILF1 orthologs encoded by porcine lymphotropic herpesviruses (PLHV BILFs). This study aimed to understand the detailed mechanisms of BILF1 receptor constitutive internalization, to explore the translational potential of PLHV BILFs compared with EBV-BILF1

Repurposing of antiparasitic drugs for Candidate SARS-CoV-2 Main Protease Inhibitors by combined in silico Method

The SARS-CoV-2 outbreak that is spreading rapidly around the world requires urgently effective treatments. Therefore, in silico drug repurposing represents a powerful strategy to enable the acceleration of the identification of drug candidates with already known safety profiles. The SARS-CoV-2 main protease is essential for viral replication and an attractive drug target. This study used the virtual screening protocol with both long-range and short-range interactions to select candidate SARS-CoV-2 main protease inhibitors. The Informational spectrum method developed for small molecules was first applied for searching the Drugbank database of antiparasitic agents and further followed by molecular docking. After in silico screening of drug space, we propose several drugs as potential SARS-CoV-2 main protease inhibitors for further experimental testing.Special Edition of Book of Abstract