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Ebola viral disease (EVD) is a highly infectious and potentially fatal illness with a case fatality rate ranging from 25% to 90%. To effectively control its spread, there is a need for rapid, reliable and lowcost point-of-care (P OC) diagnostic tests. While various EVD diagnostic tests exist, few are P OC tests, and many are not cost-effective. The use of antibodies in these tests has limitations, prompting the exploration of aptamers as potential alternatives. Various proteins from the Ebola virus (EBOV) proteome, including EBOV nucleoprotein (NP), are considered viable targets for diagnostic assays. A previous study identified three aptamers (Apt1. Apt2 and Apt3) with high affinity for EBOV NP using systemic evolution of ligands by exponential enrichment (SELEX). This study aimed to employ in silico methods, such as Phyre2, RNAfold, RNAComposer, HADDOCK and GROMACS, to model the structures of EBOV NP and the aptamers, and to investigate their binding. The in silico analysis revealed successful binding of all the three aptamers to EBOV NP, with a suggested ranking of Apt1 > Apt2 > Apt3 based on binding affinity. Microscale thermophoresis (MST) analysis confirmed the binding, providing dissociation constants of 25 ± 2.84, 56 ± 2.76 and 140 ±3.69 nM for Apt1, Apt2 and Apt3, respectively. The study shows that the findings of the in silico analysis was in agreement with the MST analysis. Inclusion of these in silico approaches in diagnostic assay development can expedite the selection of candidate aptamers, potentially overcoming challenges associated with aptamer application in diagnostics.Communicated by Ramaswamy H. Sarma.

The exponential increase in cases and mortality of coronavirus disease (COVID-19) has called for a need to develop drugs to treat this infection. Using in silico and molecular docking approaches, this study investigated the inhibitory effects of Pradimicin A, Lamivudine, Plerixafor and Lopinavir against SARS-CoV-2 M pro . ADME/Tox of the ligands, pharmacophore hypothesis of the co-crystalized ligand and the receptor, and docking studies were carried out on different modules of Schrodinger (2019-4) Maestro v12.2. Among the ligands subjected to ADME/Tox by QikProp, Lamivudine demonstrated drug-like physico-chemical properties. A total of five pharmacophore binding sites (A3, A4, R9, R10, and R11) were predicted from the co-crystalized ligand and the binding cavity of the SARS-CoV-2 M pro . The docking result showed that Lopinavir and Lamivudine bind with a higher affinity and lower free energy than the standard ligand having a glide score of -9.2 kcal/mol and -5.3 kcal/mol, respectively. Plerixafor and Pradimicin A have a glide score of -3.7 kcal/mol and -2.4 kcal/mol, respectively, which is lower than the co-crystallized ligand with a glide score of -5.3 kcal/mol. Molecular dynamics confirmed that the ligands maintained their interaction with the protein with lower RMSD fluctuations over the trajectory period of 100 nsecs and that GLU166 residue is pivotal for binding. On the whole, present study specifies the repurposing aptitude of these molecules as inhibitors of SARS-CoV-2 M pro with higher binding scores and forms energetically stable complexes with M pro .Communicated by Ramaswamy H. Sarma.

The health sector has been on the race to find a potent therapy for coronavirus disease (COVID)-19, a diseases caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2. Repurposed anti-viral drugs have played a huge role in combating the virus, and most recently, dexamethasone (Dex) have shown its therapeutic activity in severe cases of COVID-19 patients. The study sought to provide insights on the anti-COVID-19 mechanism of Dex at both atomic and molecular level against SARS-CoV-2 targets. Computational methods were employed to predict the binding affinity of Dex to SARS-CoV-2 using the Schrodinger suite (v2020-2). The target molecules and ligand (Dex) were retrieved from PDB and PubChem, respectively. The selected targets were SARS-CoV-2 main protease (Mpro), and host secreted molecules glucocorticoid receptor, and Interleukin-6 (IL-6). Critical analyses such as Protein and ligand preparation, molecular docking, molecular dynamic (MD) simulations, and absorption, distribution, metabolism, excretion (ADME), and toxicity analyses were performed using the targets and the ligand as inputs. Dex showed stronger affinity to its theoretical (glucocorticoid) receptor with a superior docking score of -14.7 and a good binding energy value of -147.48 kcal/mol; while short hydrogen bond distances were observed in both Mpro and IL-6 when compared to glucocorticoid receptor. Based on these findings, Dex-target complexes were used to perform MD simulations to analyze Dex stability at 50 ns. This study demonstrates that Dex could bind to both the viral and host receptors as a potential drug candidate for COVID-19. To ascertain the biological fitness of this study, other SARS-CoV-2 targets should be explored. Also, the in vitro studies of dexamethasone against several SARS-CoV-2 targets warrant further investigation.Communicated by Ramaswamy H. Sarma.