In this simulation study, we present a comparison of the secondary structure of the two major alloforms of the Alzheimer's peptide (Aβ(1-40) and Aβ(1-42)) on the basis of molecular dynamics (MD) simulations on thea microsecond time scale using the two GROMOS96 force fields ffG43a2 and ffG53a6. We observe peptide and force-field related differences in the sampled conformations of Aβ(1-40) and Aβ(1-42), which we characterize in terms of NMR chemical shifts calculated from the MD trajectories and validate against the corresponding experimental NMR results. From this analysis, we can conclude that ffG53a6 is better able to model the structural propensities of Aβ(1-40) and Aβ(1-42) than ffG43a2. Furthermore, we provide a description of the influences of pH and binding of D3, a 12-residue D-enantiomeric peptide with demonstrated antiamyloid effects, on the structure of Aβ(1-42). We demonstrate that, under slightly acidic conditions, protonation of the three histidine residues in Aβ(1-42) promotes the formation of β-sheets via a reduction in electrostatic repulsion between the two terminal regions. Our studies further reveal that the binding between D3 and Aβ(1-42) is driven by electrostatic interactions between negatively charged Aβ(1-42) residues and the five positively charged arginine residues of D3. The binding of D3 was found to induce large conformational changes in the amyloid peptide, with a reduction in β-sheet units being the most significant effect recorded, possibly explaining the observed amyloid-inhibiting properties of the D-peptide.

The aggregation of amyloid-β protein (1-42) is studied at experimental concentrations using all-atom molecular dynamics simulations. We observe a fast aggregation into oligomers without significant changes in the internal structure of individual proteins. The aggregation process is characterized in terms of transition networks.

We use state-of-the-art computer-aided drug design (CADD) techniques to identify prospective inhibitors of the main protease enzyme, 3CLpro of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19. From our screening of over one million compounds including approved drugs, investigational drugs, natural products, and organic compounds, and a rescreening protocol incorporating enzyme dynamics via ensemble docking, we have been able to identify a range of prospective 3CLpro inhibitors. Importantly, some of the identified compounds had previously been reported to exhibit inhibitory activities against the 3CLpro enzyme of the closely related SARS-CoV virus. The top-ranking compounds are characterized by the presence of multiple bi- and monocyclic rings, many of them being heterocycles and aromatic, which are flexibly linked allowing the ligands to adapt to the geometry of the 3CLpro substrate site and involve a high amount of functional groups enabling hydrogen bond formation with surrounding amino acid residues, including the catalytic dyad residues H41 and C145. Among the top binding compounds we identified several tyrosine kinase inhibitors, which include a bioflavonoid, the group of natural products that binds best to 3CLpro. Another class of compounds that decently binds to the SARS-CoV-2 main protease are steroid hormones, which thus may be endogenous inhibitors and might provide an explanation for the age-dependent severity of COVID-19. Many of the compounds identified by our work show a considerably stronger binding than found for reference compounds with in vitro demonstrated 3CLpro inhibition and anticoronavirus activity. The compounds determined in this work thus represent a good starting point for the design of inhibitors of SARS-CoV-2 replication.

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The biophysical and biological properties of unprecedented anti-HIV aptamers are presented. The most active aptamer (1L) shows a significant affinity to the HIV protein gp120.

The coronavirus disease 2019 (COVID-19) pandemic is caused by an infectious novel strain of coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which was earlier referred to as 2019-nCoV. The respiratory disease is the most consequential global public health crisis of the 21st century whose level of negative impact increasingly experienced globally has not been recorded since World War II. Up till now, there has been no specific globally authorized antiviral drug, vaccines, supplement or herbal remedy available for the treatment of this lethal disease except preventive measures, supportive care and non-specific treatment options adopted in different countries via divergent approaches to halt the pandemic. However, many of these interventions have been documented to show some level of success particularly the Traditional Chinese Medicine while there is paucity of well reported studies on the impact of the widely embraced Traditional African Medicines (TAM) adopted so far for the prevention, management and treatment of COVID-19. We carried out a detailed review of publicly available data, information and claims on the potentials of indigenous plants used in Sub-Saharan Africa as antiviral remedies with potentials for the prevention and management of COVID-19. In this review, we have provided a holistic report on evidence-based antiviral and promising anti-SARS-CoV-2 properties of African medicinal plants based on in silico evidence, in vitro assays and in vivo experiments alongside the available data on their mechanistic pharmacology. In addition, we have unveiled knowledge gaps, provided an update on the effort of African Scientific community toward demystifying the dreadful SARS-CoV-2 micro-enemy of man and have documented popular anti-COVID-19 herbal claims emanating from the continent for the management of COVID-19 while the risk potentials of herb-drug interaction of antiviral phytomedicines when used in combination with orthodox drugs have also been highlighted. This review exercise may lend enough credence to the potential value of African medicinal plants as possible leads in anti-COVID-19 drug discovery through research and development.

It is widely believed that Alzheimer's disease pathogenesis is driven by the production and deposition of the amyloid-β peptide (Aβ) in the brain. In this study, we employ a combination of in silico and in vitro approaches to investigate the inhibitory properties of selected arginine-rich D-enantiomeric peptides (D-peptides) against amyloid aggregation. The D-peptides include D3, a 12-residue peptide with anti-amyloid potencies demonstrated in vitro and in vivo, RD2, a scrambled sequence of D3, as well as truncated RD2 variants. Using a global optimization method together with binding free energy calculations followed by molecular dynamics simulations, we perform a detailed analysis of D-peptide binding to Aβ monomer and a fibrillar Aβ structure. Results obtained from both molecular simulations and surface plasmon resonance experiments reveal a strong binding of D3 and RD2 to Aβ, leading to a significant reduction in the amount of β structures in both monomer and fibril, which was also demonstrated in Thioflavin T assays. The binding of the D-peptides to Aβ is driven by electrostatic interactions, mostly involving the D-arginine residues and Glu11, Glu22 and Asp23 of Aβ. Furthermore, we show that the anti-amyloid activities of the D-peptides depend on the length and sequence of the Dpeptide, its ability to form multiple weak hydrophobic interactions with Aβ, as well as the Aβ oligomer size.