The rapid and global spread of a new human coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has produced an immediate urgency to discover promising targets for the treatment of COVID-19. Here, we consider drug repurposing as an attractive approach that can facilitate the drug discovery process by repurposing existing pharmaceuticals to treat illnesses other than their primary indications. We review current information concerning the global health issue of COVID-19 including promising approved drugs, e.g., human angiotensin-converting enzyme inhibitors (hACEIs). Besides, we describe computational approaches to be used in drug repurposing and highlight examples of in-silico studies of drug development efforts against SARS-CoV-2. Alacepril and lisinopril were found to interact with human angiotensin-converting enzyme 2 (hACE2), the host entranceway for SARS-CoV-2 spike protein, through exhibiting the most acceptable rmsd_refine values and the best binding affinity through forming a strong hydrogen bond with Asn90, which is assumed to be essential for the activity, as well as significant extra interactions with other receptor-binding residues. Furthermore, molecular dynamics (MD) simulations followed by calculation of the binding free energy were also carried out for the most promising two ligand-pocket complexes from docking studies (alacepril and lisinopril) to clarify some information on their thermodynamic and dynamic properties and confirm the docking results as well. These results we obtained probably provided an excellent lead candidate for the development of therapeutic drugs against COVID-19. Eventually, animal experiments and accurate clinical trials are needed to confirm the potential preventive and treatment effect of these compounds.

A nicotinamide-based derivative was designed as an antiproliferative VEGFR-2 inhibitor with the key pharmacophoric features needed to interact with the VEGFR-2 catalytic pocket. The ability of the designed congener ((E)-N-(4-(1-(2-(4-benzamidobenzoyl)hydrazono)ethyl)phenyl)nicotinamide), compound 10, to bind with the VEGFR-2 enzyme was demonstrated by molecular docking studies. Furthermore, six various MD simulations studies established the excellent binding of compound 10 with VEGFR-2 over 100 ns, exhibiting optimum dynamics. MM-GBSA confirmed the proper binding with a total exact binding energy of −38.36 Kcal/Mol. MM-GBSA studies also revealed the crucial amino acids in the binding through the free binding energy decomposition and declared the interactions variation of compound 10 inside VEGFR-2 via the Protein–Ligand Interaction Profiler (PLIP). Being new, its molecular structure was optimized by DFT. The DFT studies also confirmed the binding mode of compound 10 with the VEGFR-2. ADMET (in silico) profiling indicated the examined compound’s acceptable range of drug-likeness. The designed compound was synthesized through the condensation of N-(4-(hydrazinecarbonyl)phenyl)benzamide with N-(4-acetylphenyl)nicotinamide, where the carbonyl group has been replaced by an imine group. The in-vitro studies were consonant with the obtained in silico results as compound 10 prohibited VEGFR-2 with an IC₅₀ value of 51 nM. Compound 10 also showed antiproliferative effects against MCF-7 and HCT 116 cancer cell lines with IC₅₀ values of 8.25 and 6.48 μM, revealing magnificent selectivity indexes of 12.89 and 16.41, respectively.

Moraxella catarrhalis (M. catarrhalis) is a Gram-negative bacterium that can cause serious respiratory tract infections and middle ear infections in children and adults. M. catarrhalis has demonstrated an increasing rate of antibiotic resistance in the last few years, thus development of an effective vaccine is a major health priority. We report here a novel designed multitope vaccine based on the mapped epitopes of the vaccine candidates filtered out of the whole proteome of M. catarrhalis. After analysis of 1615 proteins using a reverse vaccinology approach, only two proteins (outer membrane protein assembly factor BamA and LPS assembly protein LptD) were nominated as potential vaccine candidates. These proteins were found to be essential, outer membrane, virulent and non-human homologs with appropriate molecular weight and high antigenicity score. For each protein, cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL) and B cell lymphocyte (BCL) epitopes were predicted and confirmed to be highly antigenic and cover conserved regions of the proteins. The mapped epitopes constituted the base of the designed multitope vaccine where suitable linkers were added to conjugate them. Additionally, beta defensin adjuvant and pan-HLA DR-binding epitope (PADRE) peptide were also incorporated into the construct to improve the stimulated immune response. The constructed multitope vaccine was analyzed for its physicochemical, structural and immunological characteristics and it was found to be antigenic, soluble, stable, non-allergenic and have a high affinity to its target receptor. Although the in silico analysis of the current study revealed that the designed multitope vaccine has the ability to trigger a specific immune response against M. catarrhalis, additional translational research is required to confirm the effectiveness of the designed vaccine.